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  1. Virus-induced secondary bacterial infection: a concise review

    Science.gov (United States)

    Hendaus, Mohamed A; Jomha, Fatima A; Alhammadi, Ahmed H

    2015-01-01

    Respiratory diseases are a very common source of morbidity and mortality among children. Health care providers often face a dilemma when encountering a febrile infant or child with respiratory tract infection. The reason expressed by many clinicians is the trouble to confirm whether the fever is caused by a virus or a bacterium. The aim of this review is to update the current evidence on the virus-induced bacterial infection. We present several clinical as well in vitro studies that support the correlation between virus and secondary bacterial infections. In addition, we discuss the pathophysiology and prevention modes of the virus–bacterium coexistence. A search of the PubMed and MEDLINE databases was carried out for published articles covering bacterial infections associated with respiratory viruses. This review should provide clinicians with a comprehensive idea of the range of bacterial and viral coinfections or secondary infections that could present with viral respiratory illness. PMID:26345407

  2. Virus-induced secondary bacterial infection: a concise review

    Directory of Open Access Journals (Sweden)

    Hendaus MA

    2015-08-01

    Full Text Available Mohamed A Hendaus,1 Fatima A Jomha,2 Ahmed H Alhammadi3 1Department of Pediatrics, Academic General Pediatrics Division, Weill-Cornell Medical College, Hamad Medical Corporation, Doha, Qatar; 2School of Pharmacy, Lebanese International University, Khiara, Lebanon; 3Department of Pediatrics, Academic General Pediatrics Division, Weill-Cornell Medical College, Hamad Medical Corporation, Doha, Qatar Abstract: Respiratory diseases are a very common source of morbidity and mortality among children. Health care providers often face a dilemma when encountering a febrile infant or child with respiratory tract infection. The reason expressed by many clinicians is the trouble to confirm whether the fever is caused by a virus or a bacterium. The aim of this review is to update the current evidence on the virus-induced bacterial infection. We present several clinical as well in vitro studies that support the correlation between virus and secondary bacterial infections. In addition, we discuss the pathophysiology and prevention modes of the virus–bacterium coexistence. A search of the PubMed and MEDLINE databases was carried out for published articles covering bacterial infections associated with respiratory viruses. This review should provide clinicians with a comprehensive idea of the range of bacterial and viral coinfections or secondary infections that could present with viral respiratory illness. Keywords: bacteria, infection, risk, virus

  3. Rhinovirus Infection Induces Degradation of Antimicrobial Peptides and Secondary Bacterial Infection in Chronic Obstructive Pulmonary Disease

    OpenAIRE

    Patrick Mallia; Joseph Footitt; Rosa Sotero; Annette Jepson; Marco Contoli; Maria-Belen Trujillo-Torralbo; Tatiana Kebadze; Julia Aniscenko; Gregory Oleszkiewicz; Katrina Gray; Message, Simon D.; Kazuhiro Ito; Peter J Barnes; Ian M Adcock; Alberto Papi

    2012-01-01

    Rationale: Chronic obstructive pulmonary disease (COPD) exacerbations are associated with virus (mostly rhinovirus) and bacterial infections, but it is not known whether rhinovirus infections precipitate secondary bacterial infections.

  4. Bacterial Infections

    Science.gov (United States)

    ... body will learn to resist them causing antibiotic resistance. Later, you could get or spread an infection that those antibiotics cannot cure. NIH: National Institute of Allergy and Infectious Diseases

  5. Photodynamic therapy can induce non-specific protective immunity against a bacterial infection

    Science.gov (United States)

    Tanaka, Masamitsu; Mroz, Pawel; Dai, Tianhong; Kinoshita, Manabu; Morimoto, Yuji; Hamblin, Michael R.

    2012-03-01

    Photodynamic therapy (PDT) for cancer is known to induce an immune response against the tumor, in addition to its well-known direct cell-killing and vascular destructive effects. PDT is becoming increasingly used as a therapy for localized infections. However there has not to date been a convincing report of an immune response being generated against a microbial pathogen after PDT in an animal model. We have studied PDT as a therapy for bacterial arthritis caused by Staphylococcus aureus infection in the mouse knee. We had previously found that PDT of an infection caused by injection of MRSA (5X107 CFU) into the mouse knee followed 3 days later by 1 μg of Photofrin and 635- nm diode laser illumination with a range of fluences within 5 minutes, gave a biphasic dose response. The greatest reduction of MRSA CFU was seen with a fluence of 20 J/cm2, whereas lower antibacterial efficacy was observed with fluences that were either lower or higher. We then tested the hypothesis that the host immune response mediated by neutrophils was responsible for most of the beneficial antibacterial effect. We used bioluminescence imaging of luciferase expressing bacteria to follow the progress of the infection in real time. We found similar results using intra-articular methylene blue and red light, and more importantly, that carrying out PDT of the noninfected joint and subsequently injecting bacteria after PDT led to a significant protection from infection. Taken together with substantial data from studies using blocking antibodies we believe that the pre-conditioning PDT regimen recruits and stimulates neutrophils into the infected joint which can then destroy bacteria that are subsequently injected and prevent infection.

  6. Epigenetics and bacterial infections.

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    Bierne, Hélène; Hamon, Mélanie; Cossart, Pascale

    2012-12-01

    Epigenetic mechanisms regulate expression of the genome to generate various cell types during development or orchestrate cellular responses to external stimuli. Recent studies highlight that bacteria can affect the chromatin structure and transcriptional program of host cells by influencing diverse epigenetic factors (i.e., histone modifications, DNA methylation, chromatin-associated complexes, noncoding RNAs, and RNA splicing factors). In this article, we first review the molecular bases of the epigenetic language and then describe the current state of research regarding how bacteria can alter epigenetic marks and machineries. Bacterial-induced epigenetic deregulations may affect host cell function either to promote host defense or to allow pathogen persistence. Thus, pathogenic bacteria can be considered as potential epimutagens able to reshape the epigenome. Their effects might generate specific, long-lasting imprints on host cells, leading to a memory of infection that influences immunity and might be at the origin of unexplained diseases.

  7. Vimentin in Bacterial Infections

    DEFF Research Database (Denmark)

    Mak, Tim N; Brüggemann, Holger

    2016-01-01

    Despite well-studied bacterial strategies to target actin to subvert the host cell cytoskeleton, thus promoting bacterial survival, replication, and dissemination, relatively little is known about the bacterial interaction with other components of the host cell cytoskeleton, including intermediate...... filaments (IFs). IFs have not only roles in maintaining the structural integrity of the cell, but they are also involved in many cellular processes including cell adhesion, immune signaling, and autophagy, processes that are important in the context of bacterial infections. Here, we summarize the knowledge...... about the role of IFs in bacterial infections, focusing on the type III IF protein vimentin. Recent studies have revealed the involvement of vimentin in host cell defenses, acting as ligand for several pattern recognition receptors of the innate immune system. Two main aspects of bacteria...

  8. Induced release of a plant-defense volatile 'deceptively' attracts insect vectors to plants infected with a bacterial pathogen.

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    Rajinder S Mann

    Full Text Available Transmission of plant pathogens by insect vectors is a complex biological process involving interactions between the plant, insect, and pathogen. Pathogen-induced plant responses can include changes in volatile and nonvolatile secondary metabolites as well as major plant nutrients. Experiments were conducted to understand how a plant pathogenic bacterium, Candidatus Liberibacter asiaticus (Las, affects host preference behavior of its psyllid (Diaphorina citri Kuwayama vector. D. citri were attracted to volatiles from pathogen-infected plants more than to those from non-infected counterparts. Las-infected plants were more attractive to D. citri adults than non-infected plants initially; however after feeding, psyllids subsequently dispersed to non-infected rather than infected plants as their preferred settling point. Experiments with Las-infected and non-infected plants under complete darkness yielded similar results to those recorded under light. The behavior of psyllids in response to infected versus non-infected plants was not influenced by whether or not they were carriers of the pathogen. Quantification of volatile release from non-infected and infected plants supported the hypothesis that odorants mediate psyllid preference. Significantly more methyl salicylate, yet less methyl anthranilate and D-limonene, was released by infected than non-infected plants. Methyl salicylate was attractive to psyllids, while methyl anthranilate did not affect their behavior. Feeding on citrus by D. citri adults also induced release of methyl salicylate, suggesting that it may be a cue revealing location of conspecifics on host plants. Infected plants were characterized by lower levels of nitrogen, phosphorus, sulfur, zinc, and iron, as well as, higher levels of potassium and boron than non-infected plants. Collectively, our results suggest that host selection behavior of D. citri may be modified by bacterial infection of plants, which alters release of

  9. Midgut immune responses induced by bacterial infection in the silkworm, Bombyx mori

    Institute of Scientific and Technical Information of China (English)

    Lei ZHANG; Yan-wen WANG; Zhi-qiang LU‡

    2015-01-01

    题目:细菌感染引起的家蚕中肠免疫反应研究  目的:探索经喂食细菌感染引起的家蚕肠道内免疫反应变化情况。  创新点:证明了家蚕肠道内的活性氧(ROS)、一氧化氮(NO)及抗菌肽在肠道免疫反应中的重要作用。  方法:通过绿脓杆菌(Pseudomonas aeruginosa)及黑胸败血菌(Bacillus bombysepticus)喂食感染家蚕以后,统计家蚕死亡率、检测感染后不同时间肠道内过氧化氢(H2O2)及NO的水平变化;同时利用实时荧光定量聚合酶链反应(qPCR)检测中肠组织中活性氧相关基因及抗菌肽基因的转录情况。  结论:死亡率结果显示,黑胸败血菌比绿脓杆菌具有更强的致病性。活性氧检测结果显示,喂食细菌感后8 h到16 h,家蚕肠道内H2O2及NO水平显著升高。通过qPCR研究ROS相关基因的表达变化的结果显示,P. aeruginosa感染后8 h可诱导肠道内双氧化酶(Duox)及过氧化氢酶(CAT)的转录上调,而感染后16 h,P. aeruginosa可诱导NO合成关键基因(一氧化氮核酶2,NOS2)的上调表达,喂食细菌感染同样可以诱导家蚕中肠抗菌肽基因的上调表达,而抗菌肽 Glovorin 2及Glovorin 3在感染初期转录上调最为明显。实验结果进一步证明 ROS、NO及 AMP的产生在家蚕肠道免疫防御中的重要作用。%Insect gut epithelial cel s produce reactive oxygen species (ROS) and antimicrobial peptides (AMPs) to protect hosts from pathogenic microorganisms. In this study, we evaluate the pathogenicity of Pseudomonas aeru-ginosa and Bacil us bombysepticus in the silkworm, Bombyx mori. Survival curves show that B. bombysepticus is deadly when larval silkworms are infected oral y. Bacterial infection caused intestinal hydrogen peroxide (H2O2) and nitric oxide (NO) levels to increase significantly by 8 and 16 h post-infection (hpi), respectively. Real-time quantitative polymerase chain

  10. NKLP27: a teleost NK-lysin peptide that modulates immune response, induces degradation of bacterial DNA, and inhibits bacterial and viral infection.

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    Zhang, Min; Li, Mo-fei; Sun, Li

    2014-01-01

    NK-lysin is an antimicrobial protein produced by cytotoxic T lymphocytes and natural killer cells. In this study, we examined the biological property of a peptide, NKLP27, derived from tongue sole (Cynoglossus semilaevis) NK-lysin. NKLP27 is composed of 27 amino acids and shares little sequence identity with known NK-lysin peptides. NKLP27 possesses bactericidal activity against both Gram-negative and Gram-positive bacteria including common aquaculture pathogens. The bactericidal activity of NKLP27 was dependent on the C-terminal five residues, deletion of which dramatically reduced the activity of NKLP27. During its interaction with the target bacterial cells, NKLP27 destroyed cell membrane integrity, penetrated into the cytoplasm, and induced degradation of genomic DNA. In vivo study showed that administration of tongue sole with NKLP27 before bacterial and viral infection significantly reduced pathogen dissemination and replication in tissues. Further study revealed that fish administered with NKLP27 exhibited significantly upregulated expression of the immune genes including those that are known to be involved in antibacterial and antiviral defense. These results indicate that NKLP27 is a novel antimicrobial against bacterial and viral pathogens, and that the observed effect of NKLP27 on bacterial DNA and host gene expression adds new insights to the action mechanism of fish antimicrobial peptides.

  11. NKLP27: a teleost NK-lysin peptide that modulates immune response, induces degradation of bacterial DNA, and inhibits bacterial and viral infection.

    Directory of Open Access Journals (Sweden)

    Min Zhang

    Full Text Available NK-lysin is an antimicrobial protein produced by cytotoxic T lymphocytes and natural killer cells. In this study, we examined the biological property of a peptide, NKLP27, derived from tongue sole (Cynoglossus semilaevis NK-lysin. NKLP27 is composed of 27 amino acids and shares little sequence identity with known NK-lysin peptides. NKLP27 possesses bactericidal activity against both Gram-negative and Gram-positive bacteria including common aquaculture pathogens. The bactericidal activity of NKLP27 was dependent on the C-terminal five residues, deletion of which dramatically reduced the activity of NKLP27. During its interaction with the target bacterial cells, NKLP27 destroyed cell membrane integrity, penetrated into the cytoplasm, and induced degradation of genomic DNA. In vivo study showed that administration of tongue sole with NKLP27 before bacterial and viral infection significantly reduced pathogen dissemination and replication in tissues. Further study revealed that fish administered with NKLP27 exhibited significantly upregulated expression of the immune genes including those that are known to be involved in antibacterial and antiviral defense. These results indicate that NKLP27 is a novel antimicrobial against bacterial and viral pathogens, and that the observed effect of NKLP27 on bacterial DNA and host gene expression adds new insights to the action mechanism of fish antimicrobial peptides.

  12. Prostatic inflammation induces fibrosis in a mouse model of chronic bacterial infection.

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    Letitia Wong

    Full Text Available Inflammation of the prostate is strongly correlated with development of lower urinary tract symptoms and several studies have implicated prostatic fibrosis in the pathogenesis of bladder outlet obstruction. It has been postulated that inflammation induces prostatic fibrosis but this relationship has never been tested. Here, we characterized the fibrotic response to inflammation in a mouse model of chronic bacterial-induced prostatic inflammation. Transurethral instillation of the uropathogenic E. coli into C3H/HeOuJ male mice induced persistent prostatic inflammation followed by a significant increase in collagen deposition and hydroxyproline content. This fibrotic response to inflammation was accompanied with an increase in collagen synthesis determined by the incorporation of 3H-hydroxyproline and mRNA expression of several collagen remodeling-associated genes, including Col1a1, Col1a2, Col3a1, Mmp2, Mmp9, and Lox. Correlation analysis revealed a positive correlation of inflammation severity with collagen deposition and immunohistochemical staining revealed that CD45+VIM+ fibrocytes were abundant in inflamed prostates at the time point coinciding with increased collagen synthesis. Furthermore, flow cytometric analysis demonstrated an increased percentage of these CD45+VIM+ fibrocytes among collagen type I expressing cells. These data show-for the first time-that chronic prostatic inflammation induces collagen deposition and implicates fibrocytes in the fibrotic process.

  13. Enhancement of Urinary Bladder Carcinogenesis by the Role of Chronic Bacterial Infection-induced Inflammation (Imunnohistochemical and Biochemical studies

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    Gabri MS*, Ashmawy AM**, Ibrahim MA*, Hosny RM

    2012-07-01

    Full Text Available Background: Bacterial infections traditionally have not been considered major causes of cancer. Recently, however, bacteria have been linked to cancer by two mechanisms: induction of chronic inflammation and production of carcinogenic bacterial metabolites. The most specific example of the inflammatory mechanism of carcinogenesis is Escherichia coli infection. E. coli has been epidemiologically linked to urothelial carcinoma of the urinary bladder by its propensity to cause lifelong inflammation. This inflammation is in turn thought to cause cancer by inducing cell proliferation and production of mutagenic free radicals and N-nitroso compounds.Material and methods: After each 3, 6 and 9 months of daily oral administration of dibutyl amine (DBA plus sodium nitrate (nitrosamine precursors in drinking water, curcuma in grinding diet and bladder injection with E. coli, rats were sacrificed. The excited bladder were dissected, processed and stained with H&E and anti-Ki67 immunohistochemical stains. This was followed by Elisa for caspse-3 and statistical analysis.Results: The current results indicated that E. coli infection in the bladder tissues increases the carcinogenic ability of nitrosamine precursors through caused marked alteration in the form hyperplastic, dysplastic and metaplastic urothelium. Also, there was a statistically significant increase in ki67 immunoreactivity in urothelium. However, a statistically significant decrease in the concentration of caspase-3 in bladder tissue consequently caused the process of carcinogenesis. All these changes were less marked after curcuma treatment when compared with the group that not treated with curcuma. Conclusion: Bacterial infection of the urinary bladder may play a major additive and possible role in bladder carcinogenesis. Rhizome of curcuma may have a protective action during induction of urinary bladder tumors.

  14. Staphylococcus aureus-induced G2/M phase transition delay in host epithelial cells increases bacterial infective efficiency.

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    Alekseeva, Ludmila; Rault, Lucie; Almeida, Sintia; Legembre, Patrick; Edmond, Valérie; Azevedo, Vasco; Miyoshi, Anderson; Even, Sergine; Taieb, Frédéric; Arlot-Bonnemains, Yannick; Le Loir, Yves; Berkova, Nadia

    2013-01-01

    Staphylococcus aureus is a highly versatile, opportunistic pathogen and the etiological agent of a wide range of infections in humans and warm-blooded animals. The epithelial surface is its principal site of colonization and infection. In this work, we investigated the cytopathic effect of S. aureus strains from human and animal origins and their ability to affect the host cell cycle in human HeLa and bovine MAC-T epithelial cell lines. S. aureus invasion slowed down cell proliferation and induced a cytopathic effect, resulting in the enlargement of host cells. A dramatic decrease in the number of mitotic cells was observed in the infected cultures. Flow cytometry analysis revealed an S. aureus-induced delay in the G2/M phase transition in synchronous HeLa cells. This delay required the presence of live S. aureus since the addition of the heat-killed bacteria did not alter the cell cycle. The results of Western blot experiments showed that the G2/M transition delay was associated with the accumulation of inactive cyclin-dependent kinase Cdk1, a key inducer of mitosis entry, and with the accumulation of unphosphorylated histone H3, which was correlated with a reduction of the mitotic cell number. Analysis of S. aureus proliferation in asynchronous, G1- and G2-phase-enriched HeLa cells showed that the G2 phase was preferential for bacterial infective efficiency, suggesting that the G2 phase delay may be used by S. aureus for propagation within the host. Taken together, our results divulge the potential of S. aureus in the subversion of key cellular processes such as cell cycle progression, and shed light on the biological significance of S. aureus-induced host cell cycle alteration.

  15. Staphylococcus aureus-induced G2/M phase transition delay in host epithelial cells increases bacterial infective efficiency.

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    Ludmila Alekseeva

    Full Text Available Staphylococcus aureus is a highly versatile, opportunistic pathogen and the etiological agent of a wide range of infections in humans and warm-blooded animals. The epithelial surface is its principal site of colonization and infection. In this work, we investigated the cytopathic effect of S. aureus strains from human and animal origins and their ability to affect the host cell cycle in human HeLa and bovine MAC-T epithelial cell lines. S. aureus invasion slowed down cell proliferation and induced a cytopathic effect, resulting in the enlargement of host cells. A dramatic decrease in the number of mitotic cells was observed in the infected cultures. Flow cytometry analysis revealed an S. aureus-induced delay in the G2/M phase transition in synchronous HeLa cells. This delay required the presence of live S. aureus since the addition of the heat-killed bacteria did not alter the cell cycle. The results of Western blot experiments showed that the G2/M transition delay was associated with the accumulation of inactive cyclin-dependent kinase Cdk1, a key inducer of mitosis entry, and with the accumulation of unphosphorylated histone H3, which was correlated with a reduction of the mitotic cell number. Analysis of S. aureus proliferation in asynchronous, G1- and G2-phase-enriched HeLa cells showed that the G2 phase was preferential for bacterial infective efficiency, suggesting that the G2 phase delay may be used by S. aureus for propagation within the host. Taken together, our results divulge the potential of S. aureus in the subversion of key cellular processes such as cell cycle progression, and shed light on the biological significance of S. aureus-induced host cell cycle alteration.

  16. Detection of bacterial infection of agave plants by laser-induced fluorescence

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    Cervantes-Martinez, Jesus; Flores-Hernandez, Ricardo; Rodriguez-Garay, Benjamin; Santacruz-Ruvalcaba, Fernando

    2002-05-01

    Greenhouse-grown plants of Agave tequilana Weber var. azul were inoculated with Erwinia carotovora, the causal agent of stem soft rot. We investigated the laser-induced fluorescence (LIF) of agave plants to determine whether LIF can be used as a noninvasive sensing tool for pathological studies. The LIF technique was also investigated as a means of detecting the effect of the polyamine biosynthesis inhibitor beta-hydroxyethylhydrazine as a bactericide against the pathogenic bacterium Erwinia carotovora. A He-Ne laser at 632.8 nm was used as the excitation source, and in vivo fluorescence emission spectra were recorded in the 660-790-range. Fluorescence maxima were at 690 and 740 nm. The infected plants that were untreated with the bactericide showed a definite increase in fluorescence intensity at both maxima within the first three days after infection. Beginning on the fifth day, a steady decrease in fluorescence intensity was observed, with a greater effect at 740 than at 690 nm. After 30 days there was no fluorescence. The infected plants that had been treated with the bactericide showed no significant change in fluorescence compared with that of the uninfected plants. The ratio of fluorescence intensities was determined to be F 690 nm/F 740 nm for all treatments. These studies indicate that LIF measurements of agave plants may be used for the early detection of certain types of disease and for determining the effect of a bactericide on bacteria. The results also showed that fluorescence intensity ratios can be used as a reliable indicator of the progress of disease.

  17. Bacterial Nasal Infections

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    ... vestibule. Nasal furuncles may develop into a spreading infection under the skin (cellulitis) at the tip of the nose. A doctor becomes concerned about infections in this part of the face because veins ...

  18. Bacterial infections in patients with liver cirrhosis

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    Giacomo Zaccherini

    2011-07-01

    Full Text Available Bacterial infections represent a frequent complication of liver cirrhosis carrying a significantly greater risk of morbidity and mortality as compared to that observed in non-cirrhotic patients. Such unfavourable prognosis is related to the systemic complications (liver and renal failure, shock, coagulopathy, multiple organ failure induced by a series of pro-inflammatory and immunological systems which are activated by bacteria and their pathogenetic products.The epidemiology of bacterial infections in cirrhosis has changed in the last years with a marked increase of Gram+ infections and the emergence of multi-resistant bacteria.The severity of liver disease represents the major clinical factor predisposing to bacterial infections, which are asymptomatic or paucisymptomatic at presentation in almost half of the cases. Aim of this review is to summarise the clinical and therapeutic aspects of bacterial infections in cirrhotic patients. The most common sites of infection are the urinary tract, ascites, blood, lungs and soft tissues.Beside antibiotics, it has been proposed the administration of human albumin to prevent the development of renal failure in patients with spontaneous bacterial peritonitis and, more recently, the use of hydrocortisone to treat cirrhotic patients with septic shock.

  19. Bacterial Skin Infections

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    ... Japanese Espaniol Find information on medical topics, symptoms, drugs, procedures, news and more, written in everyday language. * This is ... officials say 13 cases of a potentially deadly, drug-resistant fungal infection... More News Tweets by Merck and the Merck Manuals Merck & ...

  20. Mucin dynamics in intestinal bacterial infection.

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    Sara K Lindén

    Full Text Available BACKGROUND: Bacterial gastroenteritis causes morbidity and mortality in humans worldwide. Murine Citrobacter rodentium infection is a model for gastroenteritis caused by the human pathogens enteropathogenic Escherichia coli and enterohaemorrhagic E. coli. Mucin glycoproteins are the main component of the first barrier that bacteria encounter in the intestinal tract. METHODOLOGY/PRINCIPAL FINDINGS: Using Immunohistochemistry, we investigated intestinal expression of mucins (Alcian blue/PAS, Muc1, Muc2, Muc4, Muc5AC, Muc13 and Muc3/17 in healthy and C. rodentium infected mice. The majority of the C. rodentium infected mice developed systemic infection and colitis in the mid and distal colon by day 12. C. rodentium bound to the major secreted mucin, Muc2, in vitro, and high numbers of bacteria were found in secreted MUC2 in infected animals in vivo, indicating that mucins may limit bacterial access to the epithelial surface. In the small intestine, caecum and proximal colon, the mucin expression was similar in infected and non-infected animals. In the distal colonic epithelium, all secreted and cell surface mucins decreased with the exception of the Muc1 cell surface mucin which increased after infection (p<0.05. Similarly, during human infection Salmonella St Paul, Campylobacter jejuni and Clostridium difficile induced MUC1 in the colon. CONCLUSION: Major changes in both the cell-surface and secreted mucins occur in response to intestinal infection.

  1. Bacterial clearance reverses a skewed T-cell repertoire induced by Salmonella infection.

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    Leyva-Rangel, Jessica P; de Los Angeles Hernández-Cueto, Maria; Galan-Enriquez, Carlos-Samuel; López-Medina, Marcela; Ortiz-Navarrete, Vianney

    2015-09-01

    Salmonella typhimurium invades the spleen, liver, and peripheral lymph nodes and has recently been detected in the bone marrow and thymus, resulting in a reduced thymic size and a decline in the total number of thymic cells. A specific deletion of the double-positive cell subset has been characterized, yet the export of mature T cells to the periphery remains normal. We analyzed Salmonella pathogenesis regarding thymic structure and the T-cell maturation process. We demonstrate that, despite alterations in the thymic structure, T-cell development is maintained during Salmonella infection, allowing the selection of single-positive T-cell clones expressing particular T-cell receptor beta chains (TCR-Vβ). Moreover, the treatment of infected mice with an antibiotic restored the normal thymic architecture and thymocyte subset distribution. Additionally, the frequency of TCR-Vβ usage after treatment was comparable to that in non-infected mice. However, bacteria were still recovered from the thymus after 1 month of treatment. Our data reveal that a skewed T-cell developmental process is present in the Salmonella-infected thymus that alters the TCR-Vβ usage frequency. Likewise, the post-treatment persistence of Salmonella reveals a novel function of the thymus as a potential reservoir for this infectious agent.

  2. Monocytes regulate the mechanism of T-cell death by inducing Fas-mediated apoptosis during bacterial infection.

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    Marc Daigneault

    Full Text Available Monocytes and T-cells are critical to the host response to acute bacterial infection but monocytes are primarily viewed as amplifying the inflammatory signal. The mechanisms of cell death regulating T-cell numbers at sites of infection are incompletely characterized. T-cell death in cultures of peripheral blood mononuclear cells (PBMC showed 'classic' features of apoptosis following exposure to pneumococci. Conversely, purified CD3(+ T-cells cultured with pneumococci demonstrated necrosis with membrane permeabilization. The death of purified CD3(+ T-cells was not inhibited by necrostatin, but required the bacterial toxin pneumolysin. Apoptosis of CD3(+ T-cells in PBMC cultures required 'classical' CD14(+ monocytes, which enhanced T-cell activation. CD3(+ T-cell death was enhanced in HIV-seropositive individuals. Monocyte-mediated CD3(+ T-cell apoptotic death was Fas-dependent both in vitro and in vivo. In the early stages of the T-cell dependent host response to pneumococci reduced Fas ligand mediated T-cell apoptosis was associated with decreased bacterial clearance in the lung and increased bacteremia. In summary monocytes converted pathogen-associated necrosis into Fas-dependent apoptosis and regulated levels of activated T-cells at sites of acute bacterial infection. These changes were associated with enhanced bacterial clearance in the lung and reduced levels of invasive pneumococcal disease.

  3. Tobacco use increases susceptibility to bacterial infection

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    Demuth Donald R

    2008-12-01

    Full Text Available Abstract Active smokers and those exposed to secondhand smoke are at increased risk of bacterial infection. Tobacco smoke exposure increases susceptibility to respiratory tract infections, including tuberculosis, pneumonia and Legionnaires disease; bacterial vaginosis and sexually transmitted diseases, such as chlamydia and gonorrhoea; Helicobacter pylori infection; periodontitis; meningitis; otitis media; and post-surgical and nosocomial infections. Tobacco smoke compromises the anti-bacterial function of leukocytes, including neutrophils, monocytes, T cells and B cells, providing a mechanistic explanation for increased infection risk. Further epidemiological, clinical and mechanistic research into this important area is warranted.

  4. Giardia duodenalis infection reduces granulocyte infiltration in an in vivo model of bacterial toxin-induced colitis and attenuates inflammation in human intestinal tissue.

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    Cotton, James A; Motta, Jean-Paul; Schenck, L Patrick; Hirota, Simon A; Beck, Paul L; Buret, Andre G

    2014-01-01

    Giardia duodenalis (syn. G. intestinalis, G. lamblia) is a predominant cause of waterborne diarrheal disease that may lead to post-infectious functional gastrointestinal disorders. Although Giardia-infected individuals could carry as much as 106 trophozoites per centimetre of gut, their intestinal mucosa is devoid of overt signs of inflammation. Recent studies have shown that in endemic countries where bacterial infectious diseases are common, Giardia infections can protect against the development of diarrheal disease and fever. Conversely, separate observations have indicated Giardia infections may enhance the severity of diarrheal disease from a co-infecting pathogen. Polymorphonuclear leukocytes or neutrophils (PMNs) are granulocytic, innate immune cells characteristic of acute intestinal inflammatory responses against bacterial pathogens that contribute to the development of diarrheal disease following recruitment into intestinal tissues. Giardia cathepsin B cysteine proteases have been shown to attenuate PMN chemotaxis towards IL-8/CXCL8, suggesting Giardia targets PMN accumulation. However, the ability of Giardia infections to attenuate PMN accumulation in vivo and how in turn this effect may alter the host inflammatory response in the intestine has yet to be demonstrated. Herein, we report that Giardia infection attenuates granulocyte tissue infiltration induced by intra-rectal instillation of Clostridium difficile toxin A and B in an isolate-dependent manner. This attenuation of granulocyte infiltration into colonic tissues paralled decreased expression of several cytokines associated with the recruitment of PMNs. Giardia trophozoite isolates that attenuated granulocyte infiltration in vivo also decreased protein expression of cytokines released from inflamed mucosal biopsy tissues collected from patients with active Crohn's disease, including several cytokines associated with PMN recruitment. These results demonstrate for the first time that certain

  5. Giardia duodenalis infection reduces granulocyte infiltration in an in vivo model of bacterial toxin-induced colitis and attenuates inflammation in human intestinal tissue.

    Directory of Open Access Journals (Sweden)

    James A Cotton

    Full Text Available Giardia duodenalis (syn. G. intestinalis, G. lamblia is a predominant cause of waterborne diarrheal disease that may lead to post-infectious functional gastrointestinal disorders. Although Giardia-infected individuals could carry as much as 106 trophozoites per centimetre of gut, their intestinal mucosa is devoid of overt signs of inflammation. Recent studies have shown that in endemic countries where bacterial infectious diseases are common, Giardia infections can protect against the development of diarrheal disease and fever. Conversely, separate observations have indicated Giardia infections may enhance the severity of diarrheal disease from a co-infecting pathogen. Polymorphonuclear leukocytes or neutrophils (PMNs are granulocytic, innate immune cells characteristic of acute intestinal inflammatory responses against bacterial pathogens that contribute to the development of diarrheal disease following recruitment into intestinal tissues. Giardia cathepsin B cysteine proteases have been shown to attenuate PMN chemotaxis towards IL-8/CXCL8, suggesting Giardia targets PMN accumulation. However, the ability of Giardia infections to attenuate PMN accumulation in vivo and how in turn this effect may alter the host inflammatory response in the intestine has yet to be demonstrated. Herein, we report that Giardia infection attenuates granulocyte tissue infiltration induced by intra-rectal instillation of Clostridium difficile toxin A and B in an isolate-dependent manner. This attenuation of granulocyte infiltration into colonic tissues paralled decreased expression of several cytokines associated with the recruitment of PMNs. Giardia trophozoite isolates that attenuated granulocyte infiltration in vivo also decreased protein expression of cytokines released from inflamed mucosal biopsy tissues collected from patients with active Crohn's disease, including several cytokines associated with PMN recruitment. These results demonstrate for the first time

  6. Respiratory bacterial infections in cystic fibrosis

    DEFF Research Database (Denmark)

    Ciofu, Oana; Hansen, Christine R; Høiby, Niels

    2013-01-01

    Bacterial respiratory infections are the main cause of morbidity and mortality in patients with cystic fibrosis (CF). Pseudomonas aeruginosa remains the main pathogen in adults, but other Gram-negative bacteria such as Achromobacter xylosoxidans and Stenotrophomonas maltophilia as well...

  7. Glucocorticosteroids: as Adjuvant Therapy for Bacterial Infections

    Directory of Open Access Journals (Sweden)

    WONDIM MELKAM

    2015-01-01

    Full Text Available Glucocorticoids (GCs, synthetic analogues of the natural steroid hormones, are well known for their antiinflammatory and immunosuppressive properties in the periphery. They are widely and successfully used in the treatment of autoimmune diseases, chronic inflammation, and transplant rejection. Nowadays, GCs are claimed to have a beneficial role being as adjunct therapy in various infections. Different studies have been conducted to investigate their use as adjuvant therapy for different bacterial infection. This review, therefore, summarizes various bacterial infections for which glucocorticoids are reported to be used as adjuvant therapy, strategies for administration of glucocorticoids, and challenges of using glucocorticoids as adjuvant therapy.

  8. Role of quorum sensing in bacterial infections

    Science.gov (United States)

    Castillo-Juárez, Israel; Maeda, Toshinari; Mandujano-Tinoco, Edna Ayerim; Tomás, María; Pérez-Eretza, Berenice; García-Contreras, Silvia Julieta; Wood, Thomas K; García-Contreras, Rodolfo

    2015-01-01

    Quorum sensing (QS) is cell communication that is widely used by bacterial pathogens to coordinate the expression of several collective traits, including the production of multiple virulence factors, biofilm formation, and swarming motility once a population threshold is reached. Several lines of evidence indicate that QS enhances virulence of bacterial pathogens in animal models as well as in human infections; however, its relative importance for bacterial pathogenesis is still incomplete. In this review, we discuss the present evidence from in vitro and in vivo experiments in animal models, as well as from clinical studies, that link QS systems with human infections. We focus on two major QS bacterial models, the opportunistic Gram negative bacteria Pseudomonas aeruginosa and the Gram positive Staphylococcus aureus, which are also two of the main agents responsible of nosocomial and wound infections. In addition, QS communication systems in other bacterial, eukaryotic pathogens, and even immune and cancer cells are also reviewed, and finally, the new approaches proposed to combat bacterial infections by the attenuation of their QS communication systems and virulence are also discussed. PMID:26244150

  9. Immunodiagnostic Techniques for Bacterial Infections

    Science.gov (United States)

    1981-01-01

    capsulatuni Serum Actinomvcesr israeli Serum Aspergillus fumiqatus Serum Protozoan: Trvnanosoma cruzi Serum Entameaba histolvtica Serum Trichinella sviralis...serological study of human Trypanosoma rhodesiense infections using a microscale enzyme-linked immunosorbent assay. Tropenmed. Parasitol. 26:247-251, 1975

  10. Citrobacter rodentium mouse model of bacterial infection.

    Science.gov (United States)

    Crepin, Valerie F; Collins, James W; Habibzay, Maryam; Frankel, Gad

    2016-10-01

    Infection of mice with Citrobacter rodentium is a robust model to study bacterial pathogenesis, mucosal immunology, the health benefits of probiotics and the role of the microbiota during infection. C. rodentium was first isolated by Barthold from an outbreak of mouse diarrhea in Yale University in 1972 and was 'rediscovered' by Falkow and Schauer in 1993. Since then the use of the model has proliferated, and it is now the gold standard for studying virulence of the closely related human pathogens enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC, respectively). Here we provide a detailed protocol for various applications of the model, including bacterial growth, site-directed mutagenesis, mouse inoculation (from cultured cells and after cohabitation), monitoring of bacterial colonization, tissue extraction and analysis, immune responses, probiotic treatment and microbiota analysis. The main protocol, from mouse infection to clearance and analysis of tissues and host responses, takes ∼5 weeks to complete.

  11. Periodontal diseases as bacterial infection

    Directory of Open Access Journals (Sweden)

    A. Bascones Martínez

    Full Text Available The periodontal disease is conformed by a group of illnesses affecting the gums and dental support structures. They are caused by certain bacteria found in the bacterial plaque. These bacteria are essential to the onset of illness; however, there are predisposing factors in both the host and the microorganisms that will have an effect on the pathogenesis of the illness. Periodontopathogenic bacterial microbiota is needed, but by itself, it is not enough to cause the illness, requiring the presence of a susceptible host. These diseases have been classified as gingivitis, when limited to the gums, and periodontitis, when they spread to deeper tissues. Classification of periodontal disease has varied over the years.The one used in this work was approved at the International Workshop for a Classification of Periodontal Diseases and Conditions, held in 1999. This study is an overview of the different periodontal disease syndromes. Later, the systematic use of antibiotic treatment consisting of amoxicillin, amoxicillinclavulanic acid, and metronidazole as first line coadjuvant treatment of these illnesses will be reviewed.

  12. Bacterial foodborne infections after hematopoietic cell transplantation.

    Science.gov (United States)

    Boyle, Nicole M; Podczervinski, Sara; Jordan, Kim; Stednick, Zach; Butler-Wu, Susan; McMillen, Kerry; Pergam, Steven A

    2014-11-01

    Diarrhea, abdominal pain, and fever are common among patients undergoing hematopoietic cell transplantation (HCT), but such symptoms are also typical with foodborne infections. The burden of disease caused by foodborne infections in patients undergoing HCT is unknown. We sought to describe bacterial foodborne infection incidence after transplantation within a single-center population of HCT recipients. All HCT recipients who underwent transplantation from 2001 through 2011 at the Fred Hutchinson Cancer Research Center in Seattle, Washington were followed for 1 year after transplantation. Data were collected retrospectively using center databases, which include information from transplantation, on-site examinations, outside records, and collected laboratory data. Patients were considered to have a bacterial foodborne infection if Campylobacter jejuni/coli, Listeria monocytogenes, E. coli O157:H7, Salmonella species, Shigella species, Vibrio species, or Yersinia species were isolated in culture within 1 year after transplantation. Nonfoodborne infections with these agents and patients with pre-existing bacterial foodborne infection (within 30 days of transplantation) were excluded from analyses. A total of 12 of 4069 (.3%) patients developed a bacterial foodborne infection within 1 year after transplantation. Patients with infections had a median age at transplantation of 50.5 years (interquartile range [IQR], 35 to 57), and the majority were adults ≥18 years of age (9 of 12 [75%]), male gender (8 of 12 [67%]) and had allogeneic transplantation (8 of 12 [67%]). Infectious episodes occurred at an incidence rate of 1.0 per 100,000 patient-days (95% confidence interval, .5 to 1.7) and at a median of 50.5 days after transplantation (IQR, 26 to 58.5). The most frequent pathogen detected was C. jejuni/coli (5 of 12 [42%]) followed by Yersinia (3 of 12 [25%]), although Salmonella (2 of 12 [17%]) and Listeria (2 of 12 [17%]) showed equal frequencies; no cases of Shigella

  13. Optimising Antibiotic Usage to Treat Bacterial Infections

    Science.gov (United States)

    Paterson, Iona K.; Hoyle, Andy; Ochoa, Gabriela; Baker-Austin, Craig; Taylor, Nick G. H.

    2016-11-01

    The increase in antibiotic resistant bacteria poses a threat to the continued use of antibiotics to treat bacterial infections. The overuse and misuse of antibiotics has been identified as a significant driver in the emergence of resistance. Finding optimal treatment regimens is therefore critical in ensuring the prolonged effectiveness of these antibiotics. This study uses mathematical modelling to analyse the effect traditional treatment regimens have on the dynamics of a bacterial infection. Using a novel approach, a genetic algorithm, the study then identifies improved treatment regimens. Using a single antibiotic the genetic algorithm identifies regimens which minimise the amount of antibiotic used while maximising bacterial eradication. Although exact treatments are highly dependent on parameter values and initial bacterial load, a significant common trend is identified throughout the results. A treatment regimen consisting of a high initial dose followed by an extended tapering of doses is found to optimise the use of antibiotics. This consistently improves the success of eradicating infections, uses less antibiotic than traditional regimens and reduces the time to eradication. The use of genetic algorithms to optimise treatment regimens enables an extensive search of possible regimens, with previous regimens directing the search into regions of better performance.

  14. Histologic, cytologic, and bacteriologic examinations of experimentally induced Salmonella typhimurium infection in Lewis rats

    DEFF Research Database (Denmark)

    Thygesen, P; Martinsen, C; Hougen, H P;

    2000-01-01

    Histopathologic changes, cellular composition, and bacterial spreading were studied in rat spleen after experimentally induced infection with Salmonella typhimurium.......Histopathologic changes, cellular composition, and bacterial spreading were studied in rat spleen after experimentally induced infection with Salmonella typhimurium....

  15. Common bacterial urinary tract infections in women.

    Science.gov (United States)

    Cimino, J E

    1976-09-01

    Unfortunately, there is no general consensus as to how long patients with bacteriuria or urinary tract infections should be monitored and certainly there is no agreement on how long recurrent episodes should be treated beyond ten days to two weeks. The most important points to remember are: 1. Culture the urine both at the time of therapy and during follow-up. The patient should be examined periodically for the presence of bacteruria. If bacteria cannot be eradicated, at least the physician is aware of the organism most likely causing the patient's symptoms. 2. Do not subject the patient with frequent recurrent (chronic) and complicated infections to continual antibacterial therapy, but rather, manage the acute episodes. 3. Use prophylaxis, particularly single bed-time doses for dysuria and frequency symptoms. 4. Screen for bacteriuria during pregnancy. 5. Avoid the use of catheters except where absolutely necessary. 6. Avoid systemic prophylaxis of infection in patients with catheters; rather, use closed-system drainage with antibacteri-irrigation. It is to be hoped within the next few years, studies now underway will allow specific recommendations regarding the management of asymptomatic bacteruria, the duration of therapy for recurrent infections, the prevention and treatment of L-form bacterial infections, and indications for urologic procedures.

  16. Targeted imaging of bacterial infections : advances, hurdles and hopes

    NARCIS (Netherlands)

    van Oosten, Marleen; Hahn, Markus; Crane, Lucia M. A.; Pleijhuis, Rick G.; Francis, Kevin P.; van Dijl, Jan Maarten; van Dam, Gooitzen M.

    2015-01-01

    Bacterial infections represent an increasing problem in modern health care, in particular due to ageing populations and accumulating bacterial resistance to antibiotics. Diagnosis is rarely straightforward and consequently treatment is often delayed or indefinite. Therefore, novel tools that can be

  17. Bacterial colonization or infection in chronic sinusitis.

    Science.gov (United States)

    Pandak, Nenad; Pajić-Penavić, Ivana; Sekelj, Alen; Tomić-Paradžik, Maja; Cabraja, Ivica; Miklaušić, Božana

    2011-12-01

    The aim of this study was the determination of bacteria present in maxillary and ethmoid cavities in patients with chronic sinusitis and to correlate these findings with bacteria simultaneously present in their nasopharynx. The purpose of this correlation was to establish the role of bacteria found in chronically inflamed sinuses and to evaluate if the bacteria present colonized or infected sinus mucosa. Nasopharyngeal and sinus swabs of 65 patients that underwent functional endoscopic sinus surgery were cultivated and at the same time the presence of leukocytes were determined in each swab. The most frequently found bacteria in nasopharynx were Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus spp., Streptococcus viridans and Streptococcus pneumoniae. Maxillary or ethmoidal sinus swabs yielded bacterial growth in 47 (72.31%) patients. The most frequently found bacteria in sinuses were Staphylococcus epidermidis, Staphylococcus aureus, Klebsiella spp. and Streptococci (pneumoniae, viridans and spp.). The insignificant number of leukocytes was present in each sinus and nasopharyngeal swab. Every published microbiology study of chronic sinusitis proved that sinus mucosa were colonized with bacteria and not infected, yet antibiotic therapy was discussed making no difference between infection and colonization. Chronic sinusitis should be considered a chronic inflammatory condition rather than bacterial infection, so routine antibiotic therapy should be avoided. Empiric antibiotic therapy should be prescribed only in cases when the acute exacerbation of chronic sinusitis occurs and the antibiotics prescribed should aim the usual bacteria causing acute sinusitis. In case of therapy failure, antibiotics should be changed having in mind that under certain circumstances any bacteria colonizing sinus mucosa can cause acute exacerbation of chronic sinusitis.

  18. Transcriptional response of Musca domestica larvae to bacterial infection.

    Directory of Open Access Journals (Sweden)

    Ting Tang

    Full Text Available The house fly Musca domestica, a cosmopolitan dipteran insect, is a significant vector for human and animal bacterial pathogens, but little is known about its immune response to these pathogens. To address this issue, we inoculated the larvae with a mixture of Escherichia coli and Staphylococcus aureus and profiled the transcriptome 6, 24, and 48 h thereafter. Many genes known to controlling innate immunity in insects were induced following infection, including genes encoding pattern recognition proteins (PGRPs, various components of the Toll and IMD signaling pathways and of the proPO-activating and redox systems, and multiple antimicrobial peptides. Interestingly, we also uncovered a large set of novel immune response genes including two broad-spectrum antimicrobial peptides (muscin and domesticin, which might have evolved to adapt to house-fly's unique ecological environments. Finally, genes mediating oxidative phosphorylation were repressed at 48 h post-infection, suggesting disruption of energy homeostasis and mitochondrial function at the late stages of infection. Collectively, our data reveal dynamic changes in gene expression following bacterial infection in the house fly, paving the way for future in-depth analysis of M. domestica's immune system.

  19. Bacterial infections of pulp and periodontal origin.

    Science.gov (United States)

    González-Moles, Miguel Angel; González, Nabila M

    2004-01-01

    The anatomical and structural characteristics of the pulp make this structure prone to altering as a result of, for instance, periodontal conditions (proximity), iatrogenic alterations, infections and involvement of vascular and nerve structures (it is surrounded by hard tissues that prevent expansion), to name just a few. Pulpitis is a process that courses with pain of varying intensity that allows us to determine the location of the lesion in clinical terms. Its evolution varies and may even progress to pulpar necrosis that in turn, produces neuritis-like pain. Diagnosis is established by means of clinical symptomatology and supported by X-rays, palpation of tissues at painful sites, application of electrical stimuli, heat, etc. Periodontitis is a bacterial infection originating in the apex. The most important form is the so-called acute apical periodontitis that arises as a result of a prior episode of pulpitis. It is characterized by acute pain located in the tooth, accompanied by the feeling of having a long-tooth. The patient refers being unable to chew on that side; there may be painful mobility of the tooth and an outflow of pus that alleviates symptoms. X-rays do not provide a lot of information, but may attest to a widening of the apical space. This pathology may disseminate to surrounding tissues, leading to conditions of considerable severity.

  20. Prevention and Management of Bacterial Infections in Cirrhosis

    Directory of Open Access Journals (Sweden)

    Sunil K. Taneja

    2011-01-01

    Full Text Available Patients with cirrhosis of liver are at risk of developing serious bacterial infections due to altered immune defenses. Despite the widespread use of broad spectrum antibiotics, bacterial infection is responsible for up to a quarter of the deaths of patients with liver disease. Cirrhotic patients with gastrointestinal bleed have a considerably higher incidence of bacterial infections particularly spontaneous bacterial peritonitis. High index of suspicion is required to identify infections at an early stage in the absence of classical signs and symptoms. Energetic use of antibacterial treatment and supportive care has decreased the morbidity and mortality over the years; however, use of antibiotics has to be judicious, as their indiscriminate use can lead to antibiotic resistance with potentially disastrous consequences. Preventive strategies are still in evolution and involve use of antibiotic prophylaxis in patients with gastrointestinal bleeding and spontaneous bacterial infections and selective decontamination of the gut and oropharynx.

  1. Bacterial infections in cirrhosis: A critical review andpractical guidance

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    Bacterial infection is common and accounts for majormorbidity and mortality in cirrhosis. Patients withcirrhosis are immunocompromised and increased susceptibilityto develop spontaneous bacterial infections,hospital-acquired infections, and a variety of infectionsfrom uncommon pathogens. Once infection develops,the excessive response of pro-inflammatory cytokineson a pre-existing hemodynamic dysfunction in cirrhosisfurther predispose the development of serious complicationssuch as shock, acute-on-chronic liver failure, renalfailure, and death. Spontaneous bacterial peritonitisand bacteremia are common in patients with advancedcirrhosis, and are important prognostic landmarks inthe natural history of cirrhosis. Notably, the incidenceof infections from resistant bacteria has increasedsignificantly in healthcare-associated settings. Serumbiomarkers such as procalcitonin may help to improvethe diagnosis of bacterial infection. Preventive measures(e.g. , avoidance, antibiotic prophylaxis, and vaccination),early recognition, and proper management are requiredin order to minimize morbidity and mortality of infectionsin cirrhosis.

  2. [Conjugate vaccines against bacterial infections: typhoid fever].

    Science.gov (United States)

    Paniagua, J; García, J A; López, C R; González, C R; Isibasi, A; Kumate, J

    1992-01-01

    Capsular polysaccharides have been studied as possible vaccines against infectious diseases. However, they are capable to induce only short-run protection because of their T-independent properties and they would not be protective against infection in high-risk populations. The alternative to face this problem is to develop methods to join covalently the polysaccharide and proteins to both increase the immunogenicity of and to confer the property of T-dependence to this antigen. In order to obtain a conjugate vaccine against typhoid fever, in our laboratory we have tried to synthesize a conjugate immunogen between the Vi antigen and porins from Salmonella typhi.

  3. Rapid antimicrobial susceptibility testing with electrokinetics enhanced biosensors for diagnosis of acute bacterial infections.

    Science.gov (United States)

    Liu, Tingting; Lu, Yi; Gau, Vincent; Liao, Joseph C; Wong, Pak Kin

    2014-11-01

    Rapid pathogen detection and antimicrobial susceptibility testing (AST) are required in diagnosis of acute bacterial infections to determine the appropriate antibiotic treatment. Molecular approaches for AST are often based on the detection of known antibiotic resistance genes. Phenotypic culture analysis requires several days from sample collection to result reporting. Toward rapid diagnosis of bacterial infection in non-traditional healthcare settings, we have developed a rapid AST approach that combines phenotypic culture of bacterial pathogens in physiological samples and electrochemical sensing of bacterial 16S rRNA. The assay determines the susceptibility of pathogens by detecting bacterial growth under various antibiotic conditions. AC electrokinetic fluid motion and Joule heating induced temperature elevation are optimized to enhance the sensor signal and minimize the matrix effect, which improve the overall sensitivity of the assay. The electrokinetics enhanced biosensor directly detects the bacterial pathogens in blood culture without prior purification. Rapid determination of the antibiotic resistance profile of Escherichia coli clinical isolates is demonstrated.

  4. Influenza infection suppresses NADPH oxidase-dependent phagocytic bacterial clearance and enhances susceptibility to secondary MRSA infection

    Science.gov (United States)

    Sun, Keer; Metzger, Dennis W.

    2014-01-01

    Methicillin-resistant S. aureus (MRSA) has emerged as a leading contributor to mortality during recent influenza pandemics. The mechanism for this influenza-induced susceptibility to secondary S. aureus infection is poorly understood. Here we show that innate antibacterial immunity was significantly suppressed during the recovery stage of influenza infection, despite the fact that MRSA super-infection had no significant effect on viral burdens. Compared to mice infected with bacteria alone, post-influenza MRSA infected mice exhibited impaired bacterial clearance, which was not due to defective phagocyte recruitment, but rather coincided with reduced intracellular reactive oxygen species (ROS) levels in alveolar macrophages and neutrophils. NADPH oxidase is responsible for ROS production during phagocytic bacterial killing, a process also known as oxidative burst. We found that gp91phox-containing NADPH oxidase activity in macrophages and neutrophils was essential for optimal bacterial clearance during respiratory MRSA infections. In contrast to WT animals, gp91phox−/− mice exhibited similar defects in MRSA clearance before and after influenza infection. Using gp91phox+/− mosaic mice, we further demonstrate that influenza infection inhibits a cell-intrinsic contribution of NADPH oxidase to phagocyte bactericidal activity. Together, our results establish that influenza infection suppresses NADPH oxidase-dependent bacterial clearance and leads to susceptibility to secondary MRSA infection. PMID:24563256

  5. Anti-bacterial and anti-toxic immunity induced by a killed whole-cell-cholera toxin B subunit cholera vaccine is essential for protection against lethal bacterial infection in mouse pulmonary cholera model.

    Science.gov (United States)

    Kang, S-S; Yang, J S; Kim, K W; Yun, C-H; Holmgren, J; Czerkinsky, C; Han, S H

    2013-07-01

    The lack of appropriate animal model for studying protective immunity has limited vaccine development against cholera. Here, we demonstrate a pulmonary cholera model conferred by intranasal administration of mice with live Vibrio cholerae. The bacterial components, but not cholera toxin, caused lethal and acute pneumonia by inducing massive inflammation. Intranasal immunization with Dukoral, comprising killed whole bacteria and recombinant cholera toxin B subunit (rCTB), developed both mucosal and systemic antibody responses with protection against the lethal challenge. Either rCTB-free Dukoral or rCTB alone partially protected the mice against the challenge. However, reconstitution of rCTB-free Dukoral with rCTB restored full protection. Parenteral immunization with Dukoral evoked strong systemic immunity without induction of mucosal immunity or protection from the challenge. These results suggest that both anti-bacterial and anti-toxic immunity are required for protection against V. cholerae-induced pneumonia, and this animal model is useful for pre-clinical evaluation of candidate cholera vaccines.

  6. Bacterial infections in Myd88-deficient mice.

    Science.gov (United States)

    Villano, Jason S; Rong, Fang; Cooper, Timothy K

    2014-04-01

    Three breeding colonies of Myd88(-/-) mice had a history of significant morbidity and mortality. Although strain-specific poor reproductive performance might explain neonatal death and dystocia, mice were found dead or required euthanasia because of moribundity, distended abdomen, head tilt, and seizures. Histopathology results included bacteremia, placentitis, metritis, peritonitis with abscess formation, and suppurative meningoencephalitis. Intralesional gram-negative coccobacilli were present, often in extremely high number. Cultures of samples of the cardiac blood of a mouse and from water-bottle sipper tubes provided to some affected mice grew Pseudomonas aeruginosa. In addition, affected tissues from 2 mice and feces from a third tested PCR-positive for P. aeruginosa. Although the mice had received autoclaved reverse-osmosis-purified drinking water, we suspect that the mice were inoculated with P. aeruginosa through contaminated sipper tubes. Because of the deficiency in most of the Toll-like receptor signaling pathways, these Myd88(-/-) mice were unlikely to have developed competitive innate and adaptive immune responses, resulting in bacterial infections. These clinical cases underscore the importance of understanding how genotype, phenotype and environment affect animal health. Sound husbandry and experimental practices are needed to prevent the exposure of immuno-deficient mice to pathogens.

  7. Pulmonary bacterial and fungal infections in human immunodeficiency virus patients: A study from India

    Directory of Open Access Journals (Sweden)

    K Shreevidya

    2012-01-01

    Full Text Available Background: Human Immunodeficiency Virus (HIV-reactive patients are more prone to infections. The morbidity and mortality in HIV-reactive patients is due to opportunistic infections. Most of the infections seen in Acquired Immunodeficiency Syndrome are endemic to that geographical region. Hence, this study was undertaken to document the occurrence of pulmonary bacterial and fungal infections in HIV patients. Materials and Methods: Expectorated and induced sputum samples were collected from 100 HIV-reactive patients and processed for bacterial and fungal pathogens including Pneumocystis carinii. Results: Of 100 samples, 66 were culture positive. Among the isolates, Mycobacterium tuberculosis constituted the highest number, 55 (83.3%, followed by other bacterial infections, 11 (16.6%, and fungi, 2 (3.03%. Tuberculosis patients had a CD4 count of less than 250 cells/μl with a mean count of 186 cells/μl and those with bacterial infections had a CD4 count of more than 300 cells/μl. The study showed that males were infected with HIV more than females and most of them belonged to the adult age group in the prime of their working life. Weight loss followed by fever and cough were the most common symptoms. Conclusion: M. tuberculosis is the most common opportunistic pathogen followed by bacterial pathogens infecting the lung in HIV. Low CD4 count is a dangerous signal of decreased immune status and higher chances of opportunistic infections and high mortality.

  8. Differential expression of uterine NO in pregnant and nonpregnant rats with intrauterine bacterial infection.

    Science.gov (United States)

    Fang, L; Nowicki, B; Yallampalli, C

    2001-05-01

    Previous studies have demonstrated that nitric oxide (NO) is involved in the uterine host defense against bacterial infection. In nonpregnant rats, NO production in the uterus was shown to be lower, and inducible NO synthase (NOS) expression was undetectable. However, studies in pregnant rats show abundant expression of inducible NOS with significant elevation in NO production in the uterus. We have recently reported that intrauterine Escherichia coli infection caused a localized increase in uterine NO production and inducible NOS expression in the nonpregnant rat. In our present study, we examined whether the uterine NO production, NOS expression, and uterine tumor necrosis factor-alpha protein are increased in pregnant rats with intrauterine pathogenic Escherichia coli infection. Unlike the nonpregnant state, the NO production in the infected uterine horn of pregnant rats was not significantly elevated after bacterial inoculation compared with the contralateral uterine horn. The expression of uterine NOS (types II and III) also did not show significant upregulation in the infected horn. This is in contrast to that in nonpregnant animals, in which type II NOS was induced in the uterus on infection. Moreover, intrauterine infection induced an elevated expression of tumor necrosis factor-alpha protein in the infected horn both of nonpregnant and of pregnant rats. These data suggest that the sequential stimulation of NOS expression, especially the inducible isoform, and generation of uterine NO are lacking during pregnancy despite an elevated tumor necrosis factor-alpha after infection. In summary, NO synthesis response may be maximal at pregnancy, and infection may not further induce the NO system. Present studies, together with our previous report that intrauterine infection-induced lethality in pregnancy rats was amplified with the inhibition of NO, suggest that pregnancy is a state predisposed for increased complications associated with intrauterine infection and

  9. No evidence of an increase of bacterial and viral infections following Measles, Mumps and Rubella vaccine.

    Science.gov (United States)

    Stowe, Julia; Andrews, Nick; Taylor, Brent; Miller, Elizabeth

    2009-02-25

    The suggestion that multi-antigen vaccines might overload the immune system has led to calls for single antigen vaccines. In 2003 we showed that rather than an increase there appeared to be a reduced risk of severe bacterial infection in the three months following Measles, Mumps and Rubella vaccine (MMR). The present analysis of illnesses in a general population is based on an additional 10 years of data for bacterial infections and also includes admissions with viral infections. Analyses were carried out using the self-controlled case-series method and separately for bacterial and viral infection cases, using risk periods of 0-30 days, 31-60 days and 61-90 days post MMR vaccine. An analysis was also carried out for those cases which were given MMR and Meningococcal serogroup C (MCC) vaccines concomitantly. A reduced risk was seen in the 0-30-day period for both bacterial infection (relative incidence=0.68, 95% CI 0.54-0.86) and viral infections (relative incidence=0.68, 95% CI 0.49-0.93). There was no increased risk in any period when looking at combined viral or bacterial infections or for individual infections with the single exception of an increased risk in the 31-60 days post vaccination period for herpes infections (relative incidence=1.69, 95% CI 1.06-2.70). For the children given Meningococcal group C vaccines concomitantly no significantly increased risk was seen in either the bacterial (relative incidence=0.54, 95% CI 0.26-1.13) or viral cases (relative incidence=0.46, 95% CI 0.11-1.93). Our study confirms that the MMR vaccine does not increase the risk of invasive bacterial or viral infection in the 90 days after the vaccination and does not support the hypothesis that there is an induced immune deficiency due to overload from multi-antigen vaccines.

  10. Investigation of septins using infection by bacterial pathogens.

    Science.gov (United States)

    Krokowski, S; Mostowy, S

    2016-01-01

    Investigation of the host cytoskeleton during infection by bacterial pathogens has significantly contributed to our understanding of cell biology and host defense. Work has shown that septins are recruited to the phagocytic cup as collarlike structures and enable bacterial entry into host cells. In the cytosol, septins can entrap actin-polymerizing bacteria in cage-like structures for targeting to autophagy, a highly conserved intracellular degradation process. In this chapter, we describe methods to investigate septin assembly and function during infection by bacterial pathogens. Use of these methods can lead to in-depth understanding of septin biology and suggest therapeutic approaches to combat infectious disease.

  11. The role of temperate bacteriophages in bacterial infection.

    Science.gov (United States)

    Davies, Emily V; Winstanley, Craig; Fothergill, Joanne L; James, Chloe E

    2016-03-01

    Bacteriophages are viruses that infect bacteria. There are an estimated 10(31) phage on the planet, making them the most abundant form of life. We are rapidly approaching the centenary of their identification, and yet still have only a limited understanding of their role in the ecology and evolution of bacterial populations. Temperate prophage carriage is often associated with increased bacterial virulence. The rise in use of technologies, such as genome sequencing and transcriptomics, has highlighted more subtle ways in which prophages contribute to pathogenicity. This review discusses the current knowledge of the multifaceted effects that phage can exert on their hosts and how this may contribute to bacterial adaptation during infection.

  12. Chronic filarial infection provides protection against bacterial sepsis by functionally reprogramming macrophages.

    Directory of Open Access Journals (Sweden)

    Fabian Gondorf

    2015-01-01

    Full Text Available Helminths immunomodulate their hosts and induce a regulatory, anti-inflammatory milieu that prevents allergies and autoimmune diseases. Helminth immunomodulation may benefit sepsis outcome by preventing exacerbated inflammation and severe pathology, but the influence on bacterial clearance remains unclear. To address this, mice were chronically infected with the filarial nematode Litomosoides sigmodontis (L.s. and the outcome of acute systemic inflammation caused by i.p. Escherichia coli injection was determined. L.s. infection significantly improved E. coli-induced hypothermia, bacterial clearance and sepsis survival and correlated with reduced concentrations of associated pro-inflammatory cytokines/chemokines and a less pronounced pro-inflammatory macrophage gene expression profile. Improved sepsis outcome in L.s.-infected animals was mediated by macrophages, but independent of the alternatively activated macrophage subset. Endosymbiotic Wolbachia bacteria that are present in most human pathogenic filariae, as well as L.s., signal via TLR2 and modulate macrophage function. Here, gene expression profiles of peritoneal macrophages from L.s.-infected mice revealed a downregulation of genes involved in TLR signaling, and pulsing of macrophages in vitro with L.s. extract reduced LPS-triggered activation. Subsequent transfer improved sepsis outcome in naïve mice in a Wolbachia- and TLR2-dependent manner. In vivo, phagocytosis was increased in macrophages from L.s.-infected wild type, but not TLR2-deficient animals. In association, L.s. infection neither improved bacterial clearance in TLR2-deficient animals nor ameliorated E. coli-induced hypothermia and sepsis survival. These results indicate that chronic L.s. infection has a dual beneficial effect on bacterial sepsis, reducing pro-inflammatory immune responses and improving bacterial control. Thus, helminths and their antigens may not only improve the outcome of autoimmune and allergic diseases

  13. Do bacterial vaginosis and chlamydial infection affect serum cytokine level?

    Directory of Open Access Journals (Sweden)

    Bogavac Mirjana

    2010-01-01

    Full Text Available Introduction. Serbia is the country with extremely low birth rate and a relatively high percentage of preterm deliveries (8%. With this in mind, discovering new diagnostic methods that could be used for the prediction of preterm delivery is of great importance. In this study we tried to determine whether bacterial vaginosis and chlamydial infection could provoke preterm delivery by activation of systemic cytokine network. Objective. The aim of this study was to determine serum levels of proinflammatory cytokines (IL-1β, IL-8, IFN-γ, IL-6 and TNF-α in pregnant women with symptoms of preterm delivery and to make correlation between these parameters and the presence of bacterial vaginosis or chlamydial infection. Method. In the serum of 35 pregnant women, which were divided in groups according to the presence or absence of bacterial vaginosis and chlamydial infection, commercial ELISA tests for proinflammatory cytokines were performed. Results. The serum level of IFN-γ was significantly increased in pregnant women having chlamydial infection, as well as the level of IL-1β in women with bacterial vaginosis. The levels of TNF-α, IL-6 and IL-8 were not significantly different between the investigated groups. Conclusion. The preliminary results obtained in this research point out the possibility that not only intrauterine or systemic infections, but also bacterial vaginosis and chlamydial infection can cause a partial activation of systemic cytokine network and contribute to the occurrence of preterm delivery.

  14. The impact of HIV infection on blood leukocyte responsiveness to bacterial stimulation in asymptomatic patients and patients with bloodstream infection

    Directory of Open Access Journals (Sweden)

    Michaëla A M Huson

    2016-05-01

    Full Text Available Introduction: HIV-induced changes in cytokine responses to bacteria may influence susceptibility to bacterial infections and the consequent inflammatory response. Methods: We examined the impact of HIV on whole blood responsiveness to bacterial stimulation in asymptomatic subjects and patients with bacterial bloodstream infection (BSI. Whole blood was stimulated ex vivo with two bacterial Toll-like receptor agonists (lipopolysaccharide and lipoteichoic acid and two pathogens (Streptococcus pneumoniae and non-typhoidal Salmonella, which are relevant in HIV-positive patients. Production of interferon-γ, tumour necrosis factor-α, interleukin-1β and interleukin-6 was used as a read-out. Results: In asymptomatic subjects, HIV infection was associated with reduced interferon-γ, release after stimulation and priming of the pro-inflammatory cytokine response to non-typhoidal Salmonella. In patients with BSI, we found no such priming effect, nor was there evidence for more profound sepsis-induced immunosuppression in BSI patients with HIV co-infection. Conclusions: These results suggest a complex effect of HIV on leukocyte responses to bacteria. However, in patients with sepsis, leukocyte responses were equally blunted in patients with and without HIV infection.

  15. Multiple drug resistance and bacterial infection

    Institute of Scientific and Technical Information of China (English)

    Asad U Khan

    2008-01-01

    Drug resistance is becoming a great problem in developing countries due to excessive use and misuse of antibi-otics.The emergence of new pathogenic strains with resistance developed against most of the antibiotics which may cause,difficult to treat infection.To understand the current scenario in different mode of infection is most important for the clinicians and medical practitioners.This article summarized some common infections and an-tibiotic resistance pattern found among these pathogens.

  16. Strategies for combating bacterial biofilm infections

    Institute of Scientific and Technical Information of China (English)

    Hong Wu; Claus Moser; Heng-Zhuang Wang; Niels Hiby; Zhi-Jun Song

    2015-01-01

    Formation of biofilm is a survival strategy for bacteria and fungi to adapt to their living environment, especially in the hostile environment. Under the protection of biofilm, microbial cells in biofilm become tolerant and resistant to antibiotics and the immune responses, which increases the difficulties for the clinical treatment of biofilm infections. Clinical and laboratory investigations demonstrated a perspicuous correlation between biofilm infection and medical foreign bodies or indwelling devices. Clinical observations and experimental studies indicated clearly that antibiotic treatment alone is in most cases insufficient to eradicate biofilm infections. Therefore, to effectively treat biofilm infections with currently available antibiotics and evaluate the outcomes become important and urgent for clinicians. The review summarizes the latest progress in treatment of clinical biofilm infections and scientific investigations, discusses the diagnosis and treatment of different biofilm infections and introduces the promising laboratory progress, which may contribute to prevention or cure of biofilm infections. We conclude that, an efficient treatment of biofilm infections needs a well-established multidisciplinary collaboration, which includes removal of the infected foreign bodies, selection of biofilm-active, sensitive and well-penetrating antibiotics, systemic or topical antibiotic administration in high dosage and combinations, and administration of anti-quorum sensing or biofilm dispersal agents.

  17. Relationship between Intrauterine Bacterial Infection and Early Embryonic Developmental Arrest

    Institute of Scientific and Technical Information of China (English)

    Shao-Fei Yan; Xin-Yan Liu; Yun-Fei Cheng; Zhi-Yi Li; Jie Ou; Wei Wang; Feng-Qin Li

    2016-01-01

    Background:Early embryonic developmental arrest is the most commonly understudied adverse outcome of pregnancy.The relevance of intrauterine infection to spontaneous embryonic death is rarely studied and remains unclear.This study aimed to investigate the relationship between intrauterine bacterial infection and early embryonic developmental arrest.Methods:Embryonic chorion tissue and uterine swabs for bacterial detection were obtained from 33 patients who underwent artificial abortion (control group) and from 45 patients who displayed early embryonic developmental arrest (trial group).Results:Intrauterine bacterial infection was discovered in both groups.The infection rate was 24.44% (11/45) in the early embryonic developmental arrest group and 9.09% (3/33) in the artificial abortion group.Classification analysis revealed that the highest detection rate for Micrococcus luteus in the early embryonic developmental arrest group was 13.33% (6/45),and none was detected in the artificial abortion group.M.luteus infection was significantly different between the groups (P < 0.05 as shown by Fisher's exact test).In addition,no correlation was found between intrauterine bacterial infection and history of early embryonic developmental arrest.Conclusions:M.luteus infection is related to early embryonic developmental arrest and might be one of its causative factors.

  18. TBK1 protects vacuolar integrity during intracellular bacterial infection.

    Directory of Open Access Journals (Sweden)

    Andrea L Radtke

    2007-03-01

    Full Text Available TANK-binding kinase-1 (TBK1 is an integral component of Type I interferon induction by microbial infection. The importance of TBK1 and Type I interferon in antiviral immunity is well established, but the function of TBK1 in bacterial infection is unclear. Upon infection of murine embryonic fibroblasts with Salmonella enterica serovar Typhimurium (Salmonella, more extensive bacterial proliferation was observed in tbk1(-/- than tbk1(+/+ cells. TBK1 kinase activity was required for restriction of bacterial infection, but interferon regulatory factor-3 or Type I interferon did not contribute to this TBK1-dependent function. In tbk1(-/-cells, Salmonella, enteropathogenic Escherichia coli, and Streptococcus pyogenes escaped from vacuoles into the cytosol where increased replication occurred, which suggests that TBK1 regulates the integrity of pathogen-containing vacuoles. Knockdown of tbk1 in macrophages and epithelial cells also resulted in increased bacterial localization in the cytosol, indicating that the role of TBK1 in maintaining vacuolar integrity is relevant in different cell types. Taken together, these data demonstrate a requirement for TBK1 in control of bacterial infection distinct from its established role in antiviral immunity.

  19. The role of bacterial biofilms in chronic infections

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas

    2013-01-01

    treatment depends on accurate and fast diagnosis. However, in cases where the bacteria succeed in forming a biofilm within the human host, the infection often turns out to be untreatable and will develop into a chronic state. The important hallmarks of chronic biofilm-based infections are extreme resistance...... to antibiotics and many other conventional antimicrobial agents, and an extreme capacity for evading the host defences. In this thesis, I will assemble the current knowledge on biofilms with an emphasis on chronic infections, guidelines for diagnosis and treatment of these infections, before relating this to my...... previous research into the area of biofilms. I will present evidence to support a view that the biofilm lifestyle dominates chronic bacterial infections, where bacterial aggregation is the default mode, and that subsequent biofilm development progresses by adaptation to nutritional and environmental...

  20. Update and actual trends on bacterial infections following liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Jose Luis del Pozo

    2008-01-01

    Recent advances in effective antimicrobial prophylactic strategies have led to a decline in the incidence of opportunistic infections in liver transplant recipients.However, morbidity and mortality due to infectious diseases remain as major problems. Bacterial infections occurring early after transplant are mainly related to the technical aspects of the procedure. By contrast,after the first postoperative days and beyond, the nature and variety of infectious complications change.Opportunistic bacterial infections are uncommon after 6 mo in patients receiving stable and reduced maintenance doses of immunosuppression with good graft function and little is documented about these cases in the literature. Transplant recipients may be more susceptible to some pathogens, such as the Nocardia species, Legionella species, Listeria monocytogenes , Mycoplasma species, Salmonella species or Rhodococcus equi. Respiratory infections due to capsulated bacteria, such as Streptococcus pneumoniae and Haemophilus influenza, can be lifethreatening if not promptly treated in this population.These late bacterial infections may be very difficult to recognize and treat in this population. In this article,we review what has been described in the literature with regards to late bacterial infections following liver transplantation.

  1. Strategies for combating bacterial biofilm infections

    DEFF Research Database (Denmark)

    Wu, Hong; Moser, Claus Ernst; Wang, Heng-Zhuang

    2015-01-01

    Formation of biofilm is a survival strategy for bacteria and fungi to adapt to their living environment, especially in the hostile environment. Under the protection of biofilm, microbial cells in biofilm become tolerant and resistant to antibiotics and the immune responses, which increases...... the difficulties for the clinical treatment of biofilm infections. Clinical and laboratory investigations demonstrated a perspicuous correlation between biofilm infection and medical foreign bodies or indwelling devices. Clinical observations and experimental studies indicated clearly that antibiotic treatment...... alone is in most cases insufficient to eradicate biofilm infections. Therefore, to effectively treat biofilm infections with currently available antibiotics and evaluate the outcomes become important and urgent for clinicians. The review summarizes the latest progress in treatment of clinical biofilm...

  2. Catabolism of host-derived compounds during extracellular bacterial infections.

    Science.gov (United States)

    Meadows, Jamie A; Wargo, Matthew J

    2014-02-01

    Efficient catabolism of host-derived compounds is essential for bacterial survival and virulence. While these links in intracellular bacteria are well studied, such studies in extracellular bacteria lag behind, mostly for technical reasons. The field has identified important metabolic pathways, but the mechanisms by which they impact infection and in particular, establishing the importance of a compound's catabolism versus alternate metabolic roles has been difficult. In this review we will examine evidence for catabolism during extracellular bacterial infections in animals and known or potential roles in virulence. In the process, we point out key gaps in the field that will require new or newly adapted techniques.

  3. Innate Immune Sensors and Gastrointestinal Bacterial Infections

    Directory of Open Access Journals (Sweden)

    Georgina L. Hold

    2011-01-01

    Full Text Available The gastrointestinal microbiota is a major source of immune stimulation. The interaction between host pattern-recognition receptors and conserved microbial ligands profoundly influences infection dynamics. Identifying and understanding the nature of these interactions is a key step towards obtaining a clearer picture of microbial pathogenesis. These interactions underpin a complex interplay between microbe and host that has far reaching consequences for both. Here, we review the role of pattern recognition receptors in three prototype diseases affecting the stomach, the small intestine, and large intestine, respectively (Helicobacter pylori infection, Salmonella infection, and inflammatory bowel disease. Specifically, we review the nature and impact of pathogen:receptor interactions, their impact upon pathogenesis, and address the relevance of pattern recognition receptors in the development of therapies for gastrointestinal diseases.

  4. Combinations of bacterial species in endodontic infections

    NARCIS (Netherlands)

    Peters, LB; Wesselink, P.R.; van Winkelhoff, AJ

    2002-01-01

    Aim This study was undertaken to investigate combinations of bacteria found in root-canal infections of teeth with periapical bone destruction without clinical signs and symptoms. Methodology Endodontic samples from 58 root canals were cultured anaerobically and microorganisms were counted and ident

  5. Sustainable strategies for treatment of bacterial infections

    DEFF Research Database (Denmark)

    Molin, Søren

    2014-01-01

    Resistance to antibiotics and the consequential failures of treatment based on antibiotics makes microbial infections a major threat to human health. This problem combined with rapidly increasing life-style disease problems challenge our healtcare system as well as the pharma industry, and if we do...

  6. Prevalence of bacterial pathogens causing ocular infections in South India

    Directory of Open Access Journals (Sweden)

    Ramesh S

    2010-04-01

    Full Text Available Background / Aims: The eye may be infected from external sources or through intra-ocular invasion of micro-organisms carried by the blood stream. This study was undertaken to isolate and identify the specific bacterial pathogens causing ocular infections and to determine their in-vitro antibacterial susceptibilities to commonly used antibacterial agents. Materials and Methods: A retrospective analysis of all patients with clinically diagnosed bacterial ocular infections such as blepharitis, conjunctivitis, internal and external hordeolum, suppurative scleritis, canaliculitis, keratitis, dacryocystitis, preseptal cellulitis, endophthalmitis and panophthalmitis presenting between January 2005 and December 2005 was performed. Extra-ocular and intra-ocular specimens were collected and were subjected to direct microscopy and culture. Results: A total of 756 patients with bacterial ocular infections were analyzed, of which 462(61% eyes had adnexal bacterial infection, 217(28.7% had corneal infection, 6 (0.8% had scleral involvement and the remaining 71(9.39% eyes had infection of the intra-ocular tissues. The predominant bacterial species isolated was S. aureus (195 of 776; 25% followed by S. pneumoniae (169 of 776; 21.78% and coagulase negative staphylococci (142 of 776; 18.3%. The largest number of gram-positive isolates were susceptible to cefazolin (545 of 624; 87.34%, chloramphenicol (522 of 624; 83.65% and gatifloxacin (511 of 624; 81.89% and gram-negative isolates were to amikacin (127 of 136; 93.38%, gatifloxacin (125 of 136; 91.91% and ofloxacin (119 of 136; 87.5%, while aerobic actinomycetes were to amikacin (100%, gatifloxacin (14 of 16; 87.5%, chloramphenicol (14 of 16; 87.5% and ofloxacin (13 of 16; 81.25%. Conclusions: S. aureus frequently causes infections of eyelids and conjunctiva, S. pneumoniae of lacrimal apparatus and cornea and coagulase negative staphylococci causes intra-ocular infections. Of all routinely used antibacterials

  7. A Survey of Bacterial Infections in Bone Marrow Transplant Recipients

    Directory of Open Access Journals (Sweden)

    MH Shirazi

    2007-09-01

    Full Text Available "nBackground: Bone marrow transplant (BMT recipients are prone to bacterial, viral and fungal infections. Bacterial infec­tion is considered as one of the common and serious complications in bone marrow transplant recipients. The aim of this study was to determine the rate of bacterial infections in bone marrow transplant recipients."nMethods: Fifty-two blood and 25 catheter samples were obtained from 23 patients who were hospitalized in bone marrow trans­plantation unit in Shariati Hospital in Tehran. Bacterial strains were isolated and identified by the standard conven­tional bacteriological methods. Antimicrobial susceptibility was performed according to the guidelines from NCCLS using 18 different antibiotics."nResults:  The strains of Staphylococci, Streptococcus viridans, Pseudomonas aeruginosa and Escherichia coli were isolated from 8(66.7%, 1(8.3%, 2 (16.7% and the 1(8.3% cases, respectively."nConclusion: Current study indicated that the bacterial infections particularly those caused by the Gram-positive cocci were still as important problem in bone marrow transplant.

  8. Gram-Negative Bacterial Wound Infections

    Science.gov (United States)

    2015-05-01

    determine the minimal inhibitory concentrations ( MIC ) of antimicrobial agents used in human medicine. Furthermore, it was recently reported that the A...approach, but also support the implementation of studies using a well-established wound infection model using mice and pigs that will be conducted in the...identification, antibiograms, and MIC were deter- mined using the Vitek 2 (bioMérieux, France) and Phoenix (Becton, Dickinson and Co., Franklin Lakes

  9. Glucocorticosteroids: as Adjuvant Therapy for Bacterial Infections

    OpenAIRE

    2015-01-01

    Glucocorticoids (GCs), synthetic analogues of the natural steroid hormones, are well known for their antiinflammatory and immunosuppressive properties in the periphery. They are widely and successfully used in the treatment of autoimmune diseases, chronic inflammation, and transplant rejection. Nowadays, GCs are claimed to have a beneficial role being as adjunct therapy in various infections. Different studies have been conducted to investigate their use as adjuvant therapy for different bact...

  10. Respiratory viral infection predisposing for bacterial disease : a concise review

    NARCIS (Netherlands)

    Hament, JM; Kimpen, JLL; Fleer, A; Wolfs, TFW

    1999-01-01

    Although bacterial superinfection in viral respiratory disease is a clinically well documented phenomenon, the pathogenic mechanisms are still poorly understood. Recent studies have revealed some of the mechanisms involved. Physical damage to respiratory cells as a result of viral infection may lead

  11. 褪黑素对细菌脂多糖导致的宫内感染脑损伤的保护作用%Protective effect of melatonin on brain injury of intrauterine infection induced by bacterial lipopolysaccharide

    Institute of Scientific and Technical Information of China (English)

    刘利芬; 钱志红; 史明

    2011-01-01

    Objective: To investigate the effect of melatonin on free radical in brain tissues of fetal rats with intrauterine infection,explore the protective effect of melatonin on brain tissues of fetal rats with intrauterine infection. Methods: The models of cerebral palsy rat induced by intrauterine infection were established by injecting bacterial lipopolysaccharide into pregnant rats, melatonin intervention was carried out; the SD rats on the 19th day after pregnancy were selected as blank control group, intrauterine infection group and melatonin treatment group; the pregnant rats in intrauterine infection group were treated with intraperitoneal injection of bacterial lipopolysaccharide (500 μg/kg), and the pregnant rats in melatonin treatment group were treated with intraperitoneal injection of bacterial lipopolysaccharide (500 μg/kg) and melatonin ( 10 mg/kg); then the rats in each group were divided into 2 - hour group, 6 - hour group and 12 - hour group according to different observing times, 4 pregnant rats in each group; the pregnant rats in each group were executed at corresponding time points, then the brain tissues of fetal rats were obtained; the superoxide dismutase (SOD) activity, glutathione peroxidase (GSH -Px) activity and malondialdehyde (MDA) content in the brain tissues of fetal rats after homogenate were detected; HE staining was used to observe the pathological changes of brain tissues, and the differences among different groups were compared. Results: Compared with blank control group, SOD activity and GSH- Px activity of brain tissues of fetal rats in intrauterine infection group decreased, MDA content increased;with the extension of infection time, the above - mentioned changes became more obvious, there was significant difference; compared with intrauterine infection group, SOD activity and GSH - Px activity of brain tissues of fetal rats in melatonin treatment group increased, MDA content decreased. Conclusion: Brain injury of fetal rats with

  12. Arabidopsis lysin-motif proteins LYM1 LYM3 CERK1 mediate bacterial peptidoglycan sensing and immunity to bacterial infection

    Science.gov (United States)

    Willmann, Roland; Lajunen, Heini M.; Erbs, Gitte; Newman, Mari-Anne; Kolb, Dagmar; Tsuda, Kenichi; Katagiri, Fumiaki; Fliegmann, Judith; Bono, Jean-Jacques; Cullimore, Julie V.; Jehle, Anna K.; Götz, Friedrich; Kulik, Andreas; Molinaro, Antonio; Lipka, Volker; Gust, Andrea A.; Nürnberger, Thorsten

    2011-01-01

    Recognition of microbial patterns by host pattern recognition receptors is a key step in immune activation in multicellular eukaryotes. Peptidoglycans (PGNs) are major components of bacterial cell walls that possess immunity-stimulating activities in metazoans and plants. Here we show that PGN sensing and immunity to bacterial infection in Arabidopsis thaliana requires three lysin-motif (LysM) domain proteins. LYM1 and LYM3 are plasma membrane proteins that physically interact with PGNs and mediate Arabidopsis sensitivity to structurally different PGNs from Gram-negative and Gram-positive bacteria. lym1 and lym3 mutants lack PGN-induced changes in transcriptome activity patterns, but respond to fungus-derived chitin, a pattern structurally related to PGNs, in a wild-type manner. Notably, lym1, lym3, and lym3 lym1 mutant genotypes exhibit supersusceptibility to infection with virulent Pseudomonas syringae pathovar tomato DC3000. Defects in basal immunity in lym3 lym1 double mutants resemble those observed in lym1 and lym3 single mutants, suggesting that both proteins are part of the same recognition system. We further show that deletion of CERK1, a LysM receptor kinase that had previously been implicated in chitin perception and immunity to fungal infection in Arabidopsis, phenocopies defects observed in lym1 and lym3 mutants, such as peptidoglycan insensitivity and enhanced susceptibility to bacterial infection. Altogether, our findings suggest that plants share with metazoans the ability to recognize bacterial PGNs. However, as Arabidopsis LysM domain proteins LYM1, LYM3, and CERK1 form a PGN recognition system that is unrelated to metazoan PGN receptors, we propose that lineage-specific PGN perception systems have arisen through convergent evolution. PMID:22106285

  13. STUDIES ON THE TUBERCULIN REACTION AND ON SPECIFIC HYPERSENSITIVENESS IN BACTERIAL INFECTION.

    Science.gov (United States)

    Zinsser, H

    1921-10-31

    The work reported in the preceding sections justifies, we think, a number of definite conclusions. In addition to this, some of the experiments indicate a line of thought which may lead to considerable alteration in our conceptions, both of phenomena of bacterial hypersensitiveness and of infection. 1. In guinea pigs two fundamentally different types of intradermal reactions may be observed. One of these is the immediate, transitory reaction which develops in animals sensitized against proteins (horse serum, etc.) and may be regarded as one of the manifestations of general protein hypersensitiveness, or anaphylaxis; the other is the tuberculin type of skin reaction which develops more slowly, leads to a more profound injury of the tissues and is independent of anaphylaxis as ordinarily conceived. 2. The tuberculin type of hypersensitiveness (as well as probably the typhoidin, mallein, abortin reactions, etc.) does not develop at all in guinea pigs sensitized with proteins, like horse serum, etc. While this form of hypersensitiveness may eventually be induced with materials not bacterial in origin, it has been observed up to date only as a reaction of bacterial infection. 3. Methods of treatment with protein material from bacterial cultures which sensitize guinea pigs to anaphylactic reactions with the bacterial extracts, do not sensitize them to the tuberculin type of reaction. Such sensitization is easily accomplished only by infecting the animals with living organisms. No reliable method of sensitizing guinea pigs to such reactions with dead bacterial material has as yet been worked out, though a few hopeful experiments have been obtained with massive injections of large amounts of the acid-precipitable substances (nucleoproteins?) from bacterial extracts. 4. In animals made hypersensitive to the tuberculin type of reaction by infection with living bacteria, the reaction may be elicited by intradermal injections of bacterial extracts from which all coagulable

  14. Bacterial infections in cirrhosis: Role of proton pump inhibitors and intestinal permeability

    NARCIS (Netherlands)

    L.G. van Vlerken (Lotte); E.J. Huisman (Ellen); B. van Hoek (Bart); W. Renooij (W.); F.W.M. de Rooij (Felix); P.D. Siersema (Peter); K.J. van Erpecum (Karel)

    2012-01-01

    textabstractBackground Cirrhotic patients are at considerable risk for bacterial infections, possibly through increased intestinal permeability and bacterial overgrowth. Proton pump inhibitors (PPIs) may increase infection risk. We aimed to explore the potential association between PPI use and bacte

  15. PPARγ in Bacterial Infections: A Friend or Foe?

    Science.gov (United States)

    2016-01-01

    Peroxisome proliferator-activated receptor γ (PPARγ) is now recognized as an important modulator of leukocyte inflammatory responses and function. Its immunoregulatory function has been studied in a variety of contexts, including bacterial infections of the lungs and central nervous system, sepsis, and conditions such as chronic granulomatous disease. Although it is generally believed that PPARγ activation is beneficial for the host during bacterial infections via its anti-inflammatory and antibacterial properties, PPARγ agonists have also been shown to dampen the host immune response and in some cases exacerbate infection by promoting leukocyte apoptosis and interfering with leukocyte migration and infiltration. In this review we discuss the role of PPARγ and its activation during bacterial infections, with focus on the potential of PPARγ agonists and perhaps antagonists as novel therapeutic modalities. We conclude that adjustment in the dosage and timing of PPARγ agonist administration, based on the competence of host antimicrobial defenses and the extent of inflammatory response and tissue injury, is critical for achieving the essential balance between pro- and anti-inflammatory effects on the immune system.

  16. The role of bacterial biofilms in chronic infections.

    Science.gov (United States)

    Bjarnsholt, Thomas

    2013-05-01

    Acute infections caused by pathogenic bacteria have been studied extensively for well over 100 years. These infections killed millions of people in previous centuries, but they have been combated effectively by the development of modern vaccines, antibiotics and infection control measures. Most research into bacterial pathogenesis has focused on acute infections, but these diseases have now been supplemented by a new category of chronic infections caused by bacteria growing in slime-enclosed aggregates known as biofilms. Biofilm infections, such as pneumonia in cystic fibrosis patients, chronic wounds, chronic otitis media and implant- and catheter-associated infections, affect millions of people in the developed world each year and many deaths occur as a consequence. In general, bacteria have two life forms during growth and proliferation. In one form, the bacteria exist as single, independent cells (planktonic) whereas in the other form, bacteria are organized into sessile aggregates. The latter form is commonly referred to as the biofilm growth phenotype. Acute infections are assumed to involve planktonic bacteria, which are generally treatable with antibiotics, although successful treatment depends on accurate and fast diagnosis. However, in cases where the bacteria succeed in forming a biofilm within the human host, the infection often turns out to be untreatable and will develop into a chronic state. The important hallmarks of chronic biofilm-based infections are extreme resistance to antibiotics and many other conventional antimicrobial agents, and an extreme capacity for evading the host defences. In this thesis, I will assemble the current knowledge on biofilms with an emphasis on chronic infections, guidelines for diagnosis and treatment of these infections, before relating this to my previous research into the area of biofilms. I will present evidence to support a view that the biofilm lifestyle dominates chronic bacterial infections, where bacterial

  17. Severe bacterial infections in patients with non-transfusion-dependent thalassemia: prevalence and clinical risk factors

    Directory of Open Access Journals (Sweden)

    Nattiya Teawtrakul

    2015-10-01

    Conclusion: The prevalence of bacterial infection in patients with NTDT was found to be moderate. Time after splenectomy >10 years, deferoxamine therapy, and iron overload may be clinical risk factors for severe bacterial infection in patients with NTDT. Bacterial infection should be recognized in splenectomized patients with NTDT, particularly those who have an iron overload.

  18. The hematology of bacterial infections in premature infants.

    Science.gov (United States)

    Zipursky, A; Palko, J; Milner, R; Akenzua, G I

    1976-06-01

    A series of premature infants was studied for the presence of bacterial infection. On the basis of clinical evidence and bacteriological studies, they were divided into three groups in which sepsis was considered to be proven, possible, or unlikely. Band neutrophil counts were elevated most frequently in the "sepsis-proven" group and the elevation occurred usually within 24 hours of onset of signs of disease. Qualitative changes in neutrophils (Döhle bodies, toxic granulation, and vacuolization) were more frequent in the sepsis-proven group and, together with the band count, provided valuable techniques for the diagnosis of bacterial infections. Thrombocytopenia occurred frequently in the sepsis-proven group and seemed to result from increased utilization or destruction of platelets rather than failure of production. In such cases, evidence of intravascular coagulation was minimal and it was concluded that thrombocytopenia had resulted from a direct effect of the bacteria or its products on platelets and/or endothelium.

  19. Bacterial Genotoxins: Merging the DNA Damage Response into Infection Biology

    Directory of Open Access Journals (Sweden)

    Francesca Grasso

    2015-08-01

    Full Text Available Bacterial genotoxins are unique among bacterial toxins as their molecular target is DNA. The consequence of intoxication or infection is induction of DNA breaks that, if not properly repaired, results in irreversible cell cycle arrest (senescence or death of the target cells. At present, only three bacterial genotoxins have been identified. Two are protein toxins: the cytolethal distending toxin (CDT family produced by a number of Gram-negative bacteria and the typhoid toxin produced by Salmonella enterica serovar Typhi. The third member, colibactin, is a peptide-polyketide genotoxin, produced by strains belonging to the phylogenetic group B2 of Escherichia coli. This review will present the cellular effects of acute and chronic intoxication or infection with the genotoxins-producing bacteria. The carcinogenic properties and the role of these effectors in the context of the host-microbe interaction will be discussed. We will further highlight the open questions that remain to be solved regarding the biology of this unusual family of bacterial toxins.

  20. Staphylococcus aureus α toxin potentiates opportunistic bacterial lung infections.

    Science.gov (United States)

    Cohen, Taylor S; Hilliard, Jamese J; Jones-Nelson, Omari; Keller, Ashley E; O'Day, Terrence; Tkaczyk, Christine; DiGiandomenico, Antonio; Hamilton, Melissa; Pelletier, Mark; Wang, Qun; Diep, Binh An; Le, Vien T M; Cheng, Lily; Suzich, JoAnn; Stover, C Kendall; Sellman, Bret R

    2016-03-01

    Broad-spectrum antibiotic use may adversely affect a patient's beneficial microbiome and fuel cross-species spread of drug resistance. Although alternative pathogen-specific approaches are rationally justified, a major concern for this precision medicine strategy is that co-colonizing or co-infecting opportunistic bacteria may still cause serious disease. In a mixed-pathogen lung infection model, we find that the Staphylococcus aureus virulence factor α toxin potentiates Gram-negative bacterial proliferation, systemic spread, and lethality by preventing acidification of bacteria-containing macrophage phagosomes, thereby reducing effective killing of both S. aureus and Gram-negative bacteria. Prophylaxis or early treatment with a single α toxin neutralizing monoclonal antibody prevented proliferation of co-infecting Gram-negative pathogens and lethality while also promoting S. aureus clearance. These studies suggest that some pathogen-specific, antibody-based approaches may also work to reduce infection risk in patients colonized or co-infected with S. aureus and disparate drug-resistant Gram-negative bacterial opportunists.

  1. New determinants of prognosis in bacterial infections in cirrhosis

    Science.gov (United States)

    Acevedo, Juan; Fernández, Javier

    2014-01-01

    Despite major advances in the knowledge and management of liver diseases achieved in recent decades, decompensation of cirrhosis still carries a high burden of morbidity and mortality. Bacterial infections are one of the main causes of decompensation. It is very important for clinical management to be aware of the population with the highest risk of poor outcome. This review deals with the new determinants of prognosis in patients with cirrhosis and bacterial infections reported recently. Emergence of multiresistant bacteria has led to an increasing failure rate of the standard empirical antibiotic therapy recommended by international guidelines. Moreover, it has been recently reported that endothelial dysfunction is associated with the degree of liver dysfunction and, in infected patients, with the degree of sepsis. It has also been reported that relative adrenal insufficiency is frequent in the non-critically ill cirrhotic population and it is associated with a higher risk of developing infection, severe sepsis, hepatorenal syndrome and death. We advise a change in the standard empirical antibiotic therapy in patients with high risk for multiresistant infections and also to take into account endothelial and adrenal dysfunction in prognostic models in hospitalized patients with decompensated cirrhosis. PMID:24966596

  2. Klebsiella pneumoniae Siderophores Induce Inflammation, Bacterial Dissemination, and HIF-1α Stabilization during Pneumonia

    Science.gov (United States)

    Holden, Victoria I.; Breen, Paul; Houle, Sébastien; Dozois, Charles M.

    2016-01-01

    ABSTRACT Klebsiella pneumoniae is a Gram-negative pathogen responsible for a wide range of infections, including pneumonia and bacteremia, and is rapidly acquiring antibiotic resistance. K. pneumoniae requires secretion of siderophores, low-molecular-weight, high-affinity iron chelators, for bacterial replication and full virulence. The specific combination of siderophores secreted by K. pneumoniae during infection can impact tissue localization, systemic dissemination, and host survival. However, the effect of these potent iron chelators on the host during infection is unknown. In vitro, siderophores deplete epithelial cell iron, induce cytokine secretion, and activate the master transcription factor hypoxia inducible factor-1α (HIF-1α) protein that controls vascular permeability and inflammatory gene expression. Therefore, we hypothesized that siderophore secretion by K. pneumoniae directly contributes to inflammation and bacterial dissemination during pneumonia. To examine the effects of siderophore secretion independently of bacterial growth, we performed infections with tonB mutants that persist in vivo but are deficient in siderophore import. Using a murine model of pneumonia, we found that siderophore secretion by K. pneumoniae induces the secretion of interleukin-6 (IL-6), CXCL1, and CXCL2, as well as bacterial dissemination to the spleen, compared to siderophore-negative mutants at an equivalent bacterial number. Furthermore, we determined that siderophore-secreting K. pneumoniae stabilized HIF-1α in vivo and that bacterial dissemination to the spleen required alveolar epithelial HIF-1α. Our results indicate that siderophores act directly on the host to induce inflammatory cytokines and bacterial dissemination and that HIF-1α is a susceptibility factor for bacterial invasion during pneumonia. PMID:27624128

  3. Klebsiella pneumoniae Siderophores Induce Inflammation, Bacterial Dissemination, and HIF-1α Stabilization during Pneumonia

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    Victoria I. Holden

    2016-09-01

    Full Text Available Klebsiella pneumoniae is a Gram-negative pathogen responsible for a wide range of infections, including pneumonia and bacteremia, and is rapidly acquiring antibiotic resistance. K. pneumoniae requires secretion of siderophores, low-molecular-weight, high-affinity iron chelators, for bacterial replication and full virulence. The specific combination of siderophores secreted by K. pneumoniae during infection can impact tissue localization, systemic dissemination, and host survival. However, the effect of these potent iron chelators on the host during infection is unknown. In vitro, siderophores deplete epithelial cell iron, induce cytokine secretion, and activate the master transcription factor hypoxia inducible factor-1α (HIF-1α protein that controls vascular permeability and inflammatory gene expression. Therefore, we hypothesized that siderophore secretion by K. pneumoniae directly contributes to inflammation and bacterial dissemination during pneumonia. To examine the effects of siderophore secretion independently of bacterial growth, we performed infections with tonB mutants that persist in vivo but are deficient in siderophore import. Using a murine model of pneumonia, we found that siderophore secretion by K. pneumoniae induces the secretion of interleukin-6 (IL-6, CXCL1, and CXCL2, as well as bacterial dissemination to the spleen, compared to siderophore-negative mutants at an equivalent bacterial number. Furthermore, we determined that siderophore-secreting K. pneumoniae stabilized HIF-1α in vivo and that bacterial dissemination to the spleen required alveolar epithelial HIF-1α. Our results indicate that siderophores act directly on the host to induce inflammatory cytokines and bacterial dissemination and that HIF-1α is a susceptibility factor for bacterial invasion during pneumonia.

  4. A STUDY OF SECONDARY BACTERIAL INFECTIONS IN DIABETES MELLITUS

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    Tirupati Reddy Chirra

    2016-09-01

    cystitis, 9 patients had acute pyelonephritis. In Bacterial skin and mucous membrane infection, 7 otitis externa patients were there, 2 cellulitis and 4 furuncles or abscess on nose were present. In mycotic skin and mucous membrane infections, 3 were thought to have skin candida infections. There is a strong association of the infections in the diabetic mellitus patients (P<0.05. CONCLUSION Diabetes Mellitus depresses the immunity and causes a plethora of infections. This study helps the practising physicians to understand the common secondary infections and thus help them to take immediate measures to prevent further complications and arrest the natural progression of the disease.

  5. Viral and atypical bacterial infections in the outpatient pediatric cystic fibrosis clinic

    DEFF Research Database (Denmark)

    Olesen, Hanne Vebert; Nielsen, Lars P; Schiotz, Peter Oluf

    2006-01-01

    culture were recorded. RESULTS: Ninety-seven viral and 21 atypical bacterial infections were found. FEV-1 was significantly reduced during viral infection (-12.5%, p=0.048), with the exception of rhinovirus infection. A small change in FEV-1 (-3%) was seen during atypical bacterial infection (p=0...

  6. Bacterial Gibberellins Induce Systemic Resistance of Plants

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    I. N. FEKLISTOVA

    2014-06-01

    Full Text Available It is generally agreed today that some rhizosphere bacteria can ensure induced systemic resistance to pathogens. In this paper we tested the ability of gibberellins produced by rhizosphere non-pathogenic bacteria Pseudomonas aurantiaca to induce systemic resistance to alternariosis agent – Alternaria brassicicola – in oilseed rape plants.Oilseed rape (Brássica nápus is one of the most promising oil-bearing croppers. It allows improving the supply of population with vegetable oil, animal and poultry industries with high quality vegetable protein. It is used for biofuel production as well.Gibberellin preparation was isolated from liquid culture of strain Pseudomonas aurantiaca grown in 250 mL of M9 medium (48 h, 28 °C under darkroom conditions. Gibberellins were extracted according procedure described by Tien et al. (1979. Gibberellins concentration in the medium was determined by fluorometric method.Elicitor activity of bacterial metabolites – gibberellins – was analyzed in model system of artificial inoculation of oilseed rape germs with phytopathogenic fungi Alternaria brassicicola. The elicitor action efficiency was evaluated on the 15th day of oilseed rape cultivation based on the percentage of leaf surface covered by necrotic lesions.Gibberellins were shown to induce systemic resistance resulted in decreasing of oil seed plants   vulnerability by 52.7%.It is known that under the unfavorable conditions plants synthesis the reactive oxygen intermediates   which activate destructive processes. One of the first organism reactions to stress action is the change of the lipid peroxidation level. It was shown that treatment of the soil with gibberellins resulted in decreasing of the lipid peroxidation level twofold.Gibberellins were shown to have a similar effect on permeability of cell membranes for free nucleotides. The permeability of cell membranes in leaves decreased 2.8-fold at room temperature. We suggest that gibberellins

  7. The Salmonella effector AvrA mediates bacterial intracellular survival during infection in vivo.

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    Wu, Huixia; Jones, Rheinallt M; Neish, Andrew S

    2012-01-01

    The enteric pathogen Salmonella typhimurium secretes the preformed AvrA effector protein into host cells. This acetyltransferase has been shown to modulate mammalian intestinal immune and survival responses by inhibition of JNK MAPK. To study the role of this effector in natural enteric infection, we used a mouse model to compare wild-type S. typhimurium to an isogenic AvrA null Salmonella mutant. Salmonella lacking AvrA induced increased intestinal inflammation, more intense systemic cytokine responses, and increased apoptosis in epithelial cells. Increased apoptosis was also observed in extra epithelial macrophages. AvrA null-infected mice consistently showed higher bacterial burden within mucosal lymphoid tissues, spleen and liver by 5 days post infection, which indicated a more severe clinical course. To study the molecular mechanisms involved, recombinant adenoviruses expressing AvrA or mutant AvrA proteins were constructed, which showed appropriate expression and mediated the expected inhibition of JNK signalling. Cultured epithelial cells and macrophages transduced with AvrA expressing adenovirus were protected from apoptosis induced by exogenous stimuli. In conclusion, the results demonstrated that Salmonella AvrA modulates survival of infected macrophages likely via JNK suppression, and prevents macrophage death and rapid bacterial dissemination. AvrA suppression of apoptosis in infected macrophages may allow for establishment of a stable intracellular niche typical of intracellular pathogens.

  8. Scintigraphic images of bacterial infection using aptamers directly labeled with {sup 99m}Tc

    Energy Technology Data Exchange (ETDEWEB)

    Santos, S.R.; Correa, C.R.; Andrade, A.S.R., E-mail: sararoberta7@hotmail.com, E-mail: crisrcorrea@gmail.com, E-mail: antero@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil); Barros, A.L.B.; Diniz, S.O.F.; Cardoso, V.N., E-mail: brancodebarros@yahoo.com.br, E-mail: valbertcardoso@yahoo.com.br, E-mail: simoneodilia@yahoo.com.br [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Faculdade de Farmacia. Departamento de Analises Clinicas e Toxicologicas

    2015-07-01

    Staphylococcus aureus is specie of great medical importance and is the most commonly agent found in infections of soft tissues, bone infections and bone prostheses. In this study, aptamers selected to S. aureus were labeled by the direct method with {sup 99m}Tc and used for bacterial infection identification by scintigraphy. The radiolabeled aptamers radiochemical purity and stability were assessed by thin-layer chromatography (TLC). Three groups of Swiss mice (n=6) were used for the scintigraphic imaging studies. The first group was infected intramuscularly in the right thigh with S. aureus, the second group with C. albicans and the third group received zymosan to induce aseptic inflammation. After 24 h, radiolabeled aptamers (18 MBq) were injected by the tail vein. Scintigraphic images were acquired at 1 h and 4 h postinjection. The radiolabeling yield with {sup 99m}Tc was over 90%. The radiolabeled aptamers were stable in 0.9% saline, plasma and cysteine excess. The scintigraphic image profiles showed high uptake in the kidneys and bladder in all groups, indicating a main renal excretion consistent with the hydrophilic nature of the molecule. No accumulation of radioactivity was observed in the thyroid, stomach, liver and spleen, indicating acceptable levels of radiochemical impurities. The group infected with S. aureus showed a visible uptake in the infected right thigh at 1 h post-injection. For the control groups (C. albicans and zymosan) visible differences between the right and left thighs were not observed. The radiolabeled aptamers were able to distinguish aseptic inflammation from bacterial infection and bacterial from fungal infection. (author)

  9. Nanosized Selenium: A Novel Platform Technology to Prevent Bacterial Infections

    Science.gov (United States)

    Wang, Qi

    As an important category of bacterial infections, healthcare-associated infections (HAIs) are considered an increasing threat to the safety and health of patients worldwide. HAIs lead to extended hospital stays, contribute to increased medical costs, and are a significant cause of morbidity and mortality. In the United States, infections encountered in the hospital or a health care facility affect more than 1.7 million patients, cost 35.7 billion to 45 billion, and contribute to 88,000 deaths in hospitals annually. The most conventional and widely accepted method to fight against bacterial infections is using antibiotics. However, because of the widespread and sometimes inappropriate use of antibiotics, many strains of bacteria have rapidly developed antibiotic resistance. Those new, stronger bacteria pose serious, worldwide threats to public health and welfare. In 2014, the World Health Organization (WHO) reported antibiotic resistance as a global serious threat that is no longer a prediction for the future but is now reality. It has the potential to affect anyone, of any age, in any country. The most effective strategy to prevent antibiotic resistance is minimizing the use of antibiotics. In recent years, nanomaterials have been investigated as one of the potential substitutes of antibiotics. As a result of their vastly increased ratio of surface area to volume, nanomaterials will likely exert a stronger interaction with bacteria which may affect bacterial growth and propagation. A major concern of most existing antibacterial nanomaterials, like silver nanoparticles, is their potential toxicity. But selenium is a non-metallic material and a required nutrition for the human body, which is recommended by the FDA at a 53 to 60 μg daily intake. Nanosized selenium is considered to be healthier and less toxic compared with many metal-based nanomaterials due to the generation of reactive oxygen species from metals, especially heavy metals. Therefore, the objectives of

  10. Pipecolic acid enhances resistance to bacterial infection and primes salicylic acid and nicotine accumulation in tobacco.

    Science.gov (United States)

    Vogel-Adghough, Drissia; Stahl, Elia; Návarová, Hana; Zeier, Juergen

    2013-11-01

    Distinct amino acid metabolic pathways constitute integral parts of the plant immune system. We have recently identified pipecolic acid (Pip), a lysine-derived non-protein amino acid, as a critical regulator of systemic acquired resistance (SAR) and basal immunity to bacterial infection in Arabidopsis thaliana. In Arabidopsis, Pip acts as an endogenous mediator of defense amplification and priming. For instance, Pip conditions plants for effective biosynthesis of the phenolic defense signal salicylic acid (SA), accumulation of the phytoalexin camalexin, and expression of defense-related genes. Here, we show that tobacco plants respond to leaf infection by the compatible bacterial pathogen Pseudomonas syringae pv tabaci (Pstb) with a significant accumulation of several amino acids, including Lys, branched-chain, aromatic, and amide group amino acids. Moreover, Pstb strongly triggers, alongside the biosynthesis of SA and increases in the defensive alkaloid nicotine, the production of the Lys catabolites Pip and α-aminoadipic acid. Exogenous application of Pip to tobacco plants provides significant protection to infection by adapted Pstb or by non-adapted, hypersensitive cell death-inducing P. syringae pv maculicola. Pip thereby primes tobacco for rapid and strong accumulation of SA and nicotine following bacterial infection. Thus, our study indicates that the role of Pip as an amplifier of immune responses is conserved between members of the rosid and asterid groups of eudicot plants and suggests a broad practical applicability for Pip as a natural enhancer of plant disease resistance.

  11. Salmonella Infection Enhances Erythropoietin Production by the Kidney and Liver, Which Correlates with Elevated Bacterial Burdens.

    Science.gov (United States)

    Li, Lin-Xi; Benoun, Joseph M; Weiskopf, Kipp; Garcia, K Christopher; McSorley, Stephen J

    2016-10-01

    Salmonella infection profoundly affects host erythroid development, but the mechanisms responsible for this effect remain poorly understood. We monitored the impact of Salmonella infection on erythroid development and found that systemic infection induced anemia, splenomegaly, elevated erythropoietin (EPO) levels, and extramedullary erythropoiesis in a process independent of Salmonella pathogenicity island 2 (SPI2) or flagellin. The circulating EPO level was also constitutively higher in mice lacking the expression of signal-regulatory protein α (SIRPα). The expression level of EPO mRNA was elevated in the kidney and liver but not increased in the spleens of infected mice despite the presence of extramedullary erythropoiesis in this tissue. In contrast to data from a previous report, mice lacking EPO receptor (EPOR) expression on nonerythroid cells (EPOR rescued) had bacterial loads similar to those of wild-type mice following Salmonella infection. Indeed, treatment to reduce splenic erythroblasts and mature red blood cells correlated with elevated bacterial burdens, implying that extramedullary erythropoiesis benefits the host. Together, these findings emphasize the profound effect of Salmonella infection on erythroid development and suggest that the modulation of erythroid development has both positive and negative consequences for host immunity.

  12. Salmonella Infection Enhances Erythropoietin Production by the Kidney and Liver, Which Correlates with Elevated Bacterial Burdens

    Science.gov (United States)

    Li, Lin-Xi; Benoun, Joseph M.; Weiskopf, Kipp; Garcia, K. Christopher

    2016-01-01

    Salmonella infection profoundly affects host erythroid development, but the mechanisms responsible for this effect remain poorly understood. We monitored the impact of Salmonella infection on erythroid development and found that systemic infection induced anemia, splenomegaly, elevated erythropoietin (EPO) levels, and extramedullary erythropoiesis in a process independent of Salmonella pathogenicity island 2 (SPI2) or flagellin. The circulating EPO level was also constitutively higher in mice lacking the expression of signal-regulatory protein α (SIRPα). The expression level of EPO mRNA was elevated in the kidney and liver but not increased in the spleens of infected mice despite the presence of extramedullary erythropoiesis in this tissue. In contrast to data from a previous report, mice lacking EPO receptor (EPOR) expression on nonerythroid cells (EPOR rescued) had bacterial loads similar to those of wild-type mice following Salmonella infection. Indeed, treatment to reduce splenic erythroblasts and mature red blood cells correlated with elevated bacterial burdens, implying that extramedullary erythropoiesis benefits the host. Together, these findings emphasize the profound effect of Salmonella infection on erythroid development and suggest that the modulation of erythroid development has both positive and negative consequences for host immunity. PMID:27456828

  13. Peripheral T Cell Apoptosis and Its Role in Generalized Bacterial Infections: A Minireview.

    Science.gov (United States)

    Chernykh, Helen R.; Norkin, Maxim N.; Leplina, Olga Yu.; Khonina, Nataliya A.; Tihonova, Marina A.; Ostanin, Alexander A.

    2001-07-01

    In the present review we have attempted to analyze recent findings concerning apoptosis of mature peripheral T cells. The great attention is made to the factors underlying resistance or sensitivity of mature T lymphocytes to activation-induced cell death. The role of preactivation and altered costimulation is discussed in this regard. Besides, the possible role of cytokines in the modulation of T cell apoptosis is emphasized. Particular attention is paid to the studies of apoptosis disorders in the pathogenesis of generalized bacterial infections. In this connection some own results are summarized as well. To characterize T cell death and its role in the pathogenesis of bacterial infections an anti-CD3-mAb or Con A-induced apoptosis in patients with severe and generalized forms of surgical infections have been investigated. We have found a significant increase of activation-induced lymphocyte apoptosis and a high level of apoptosis in freshly isolated lymphocytes in patients with surgical infections. Alternatively, peripheral blood mononuclear cells from surgical patients without infectious complications did not exhibit a marked enhancement of activation-induced cell death. Activation-induced T cell death in surgical infections appeared to be Fas-dependent, involved reactive oxygen intermediates and was partly prevented by pro-inflammatory cytokines, among which IL-2 exhibited the most pronounced anti-apoptotic activity. Likewise, APACHE II score, as a marker of the infection severity, directly correlated with a rate of activation-induced T cell apoptosis. Accelerated T cell apoptosis at the early stage of infection was revealed in survivors and non-survivors, that appears to designate a common pathway for the restriction of systemic inflammation. At the late stage of infection altered T cell apoptosis could account for different outcomes, since the patients with lethal outcome showed 2-fold increase in activation-induced cell death compared to the opposite group

  14. Detection of intracellular bacterial communities in human urinary tract infection.

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    David A Rosen

    2007-12-01

    Full Text Available BACKGROUND: Urinary tract infections (UTIs are one of the most common bacterial infections and are predominantly caused by uropathogenic Escherichia coli (UPEC. While UTIs are typically considered extracellular infections, it has been recently demonstrated that UPEC bind to, invade, and replicate within the murine bladder urothelium to form intracellular bacterial communities (IBCs. These IBCs dissociate and bacteria flux out of bladder facet cells, some with filamentous morphology, and ultimately establish quiescent intracellular reservoirs that can seed recurrent infection. This IBC pathogenic cycle has not yet been investigated in humans. In this study we sought to determine whether evidence of an IBC pathway could be found in urine specimens from women with acute UTI. METHODS AND FINDINGS: We collected midstream, clean-catch urine specimens from 80 young healthy women with acute uncomplicated cystitis and 20 asymptomatic women with a history of UTI. Investigators were blinded to culture results and clinical history. Samples were analyzed by light microscopy, immunofluorescence, and electron microscopy for evidence of exfoliated IBCs and filamentous bacteria. Evidence of IBCs was found in 14 of 80 (18% urines from women with UTI. Filamentous bacteria were found in 33 of 80 (41% urines from women with UTI. None of the 20 urines from the asymptomatic comparative group showed evidence of IBCs or filaments. Filamentous bacteria were present in all 14 of the urines with IBCs compared to 19 (29% of 66 samples with no evidence of IBCs (p < 0.001. Of 65 urines from patients with E. coli infections, 14 (22% had evidence of IBCs and 29 (45% had filamentous bacteria, while none of the gram-positive infections had IBCs or filamentous bacteria. CONCLUSIONS: The presence of exfoliated IBCs and filamentous bacteria in the urines of women with acute cystitis suggests that the IBC pathogenic pathway characterized in the murine model may occur in humans. The

  15. Virulent bacterial infection improves aversive learning performance in Drosophila melanogaster.

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    Babin, Aurélie; Kolly, Sylvain; Kawecki, Tadeusz J

    2014-10-01

    Virulent infections are expected to impair learning ability, either as a direct consequence of stressed physiological state or as an adaptive response that minimizes diversion of energy from immune defense. This prediction has been well supported for mammals and bees. Here, we report an opposite result in Drosophila melanogaster. Using an odor-mechanical shock conditioning paradigm, we found that intestinal infection with bacterial pathogens Pseudomonas entomophila or Erwinia c. carotovora improved flies' learning performance after a 1h retention interval. Infection with P. entomophila (but not E. c. carotovora) also improved learning performance after 5 min retention. No effect on learning performance was detected for intestinal infections with an avirulent GacA mutant of P. entomophila or for virulent systemic (hemocoel) infection with E. c. carotovora. Assays of unconditioned responses to odorants and shock do not support a major role for changes in general responsiveness to stimuli in explaining the changes in learning performance, although differences in their specific salience for learning cannot be excluded. Our results demonstrate that the effects of pathogens on learning performance in insects are less predictable than suggested by previous studies, and support the notion that immune stress can sometimes boost cognitive abilities.

  16. Review: phage therapy: a modern tool to control bacterial infections.

    Science.gov (United States)

    Qadir, Muhammad Imran

    2015-01-01

    The evolution of antibiotic-resistant in bacteria has aggravated curiosity in development of alternative therapy to conventional drugs. One of the emerging drugs that can be used alternative to antibiotics is bacteriophage therapy. The use of living phages in the cure of lethal infectious life threatening diseases caused by Gram positive and Gram negative bacteria has been reported. Another development in the field of bacteriophage therapy is the use of genetically modified and non replicating phages in the treatment of bacterial infection. Genetically engineered bacteriophages can be used as adjuvant along with antibiotic therapy. Phages encoded with lysosomal enzymes are also effectual in the treatment of infectious diseases.

  17. Evaluation of localized bacterial infection using radioisotope-labeled nucleosides imaging modality

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Su Jin; Kang, Joo Hyun; Lee, Yong Jin; Lee, Tae Sup; Kim, Kwang Il; Lee, Kyo Chul; An, Gwang II; Cheon, Gi Jeong; Lim, Sang Moo [KIRAMS, Seoul (Korea, Republic of); Lim, Sang Yong [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2011-10-15

    Conventional diagnostic methods for infections are difficult to distinguish localized bacterial infections from sites of sterile inflammation. For this reason, the importance of developing methods to image bacterial infections is widely recognized. In this study to acquire bacterial infection imaging with radiolabeled nucleosides, in vitro bacterial thymidine kinase (tk) activities of Salmonella typhimurium with [{sup 18}F]FLT and [{sup 125}I]IVDU were measured and localized infections model in BALB/c mice was imaged with [{sup 18}F]FLT or [{sup 125}I]FIAU

  18. Clinical characteristics and prognostic impact of bacterial infection in hospitalized patients with alcoholic liver disease.

    Science.gov (United States)

    Park, Jin Kyoung; Lee, Chang Hun; Kim, In Hee; Kim, Seon Min; Jang, Ji Won; Kim, Seong Hun; Kim, Sang Wook; Lee, Seung Ok; Lee, Soo Teik; Kim, Dae-Ghon

    2015-05-01

    Bacterial infection is an important cause of death in patients with liver cirrhosis. The aim of this study was to investigate the clinical characteristics and prognostic impact of bacterial infection in hospitalized patients with alcoholic liver disease (ALD). We retrospectively analyzed data from 409 patients consecutively admitted to a tertiary referral center with ALD diagnosis. Of a total of 544 admissions, 133 (24.4%) cases presented with bacterial infection, of which 116 were community-acquired whereas 17 were hospital-acquired. The common types of infection were pneumonia (38%), biliary tract infection (17%), soft tissue infection (12%), and spontaneous bacterial peritonitis (9%). Diabetes, serum Na patients with ALD. Overall 30-day and 90-day mortalities in patients with bacterial infection were significantly (P patients with ALD. A thorough evaluation at admission or on clinical deterioration is required to detect possible infection with prompt management.

  19. Identification and expression profiles of multiple genes in Nile tilapia in response to bacterial infections.

    Science.gov (United States)

    Pridgeon, Julia W; Aksoy, Mediha; Klesius, Phillip H; Li, Yuehong; Mu, Xingjiang; Srivastava, Kunwar; Reddy, Gopal

    2011-11-15

    To understand the molecular mechanisms involved in response of Nile tilapia (Oreochromis niloticus) to bacterial infection, suppression subtractive cDNA hybridization technique was used to identify upregulated genes in the posterior kidney of Nile tilapia at 6h post infection with Aeromonas hydrophila. A total of 31 unique expressed sequence tags (ESTs) were identified from 192 clones of the subtractive cDNA library. Quantitative PCR revealed that nine of the 31 ESTs were significantly (ptilapia at 6h post infection with A. hydrophila at an injection dose of 10(5)CFU per fish (≈ 20% mortality). Of the nine upregulated genes, four were also significantly (ptilapia at 6h post infection with A. hydrophila at an injection dose of 10(6)CFU per fish (≈ 60% mortality). Of the four genes induced by A. hydrophila at both injection doses, three were also significantly (ptilapia at 6h post infection with Streptococcus iniae at doses of 10(6) and at 10(5)CFU per fish (≈ 70% and ≈ 30% mortality, respectively). The three genes induced by both bacteria included EST 2A05 (similar to adenylate kinase domain containing protein 1), EST 2G11 (unknown protein, shared similarity with Salmo salar IgH locus B genomic sequence with e value of 0.02), and EST 2H04 (unknown protein). Significant upregulation of these genes in Nile tilapia following bacterial infections suggested that they might play important roles in host response to infections of A. hydrophila and S. iniae.

  20. Prevalence and bacterial susceptibility of hospital acquired urinary tract infection

    Directory of Open Access Journals (Sweden)

    Dias Neto José Anastácio

    2003-01-01

    Full Text Available PURPOSE: Urinary tract infection is the most common nosocomially acquired infection. It is important to know the etiology and antibiotic susceptibility infectious agents to guide the initial empirical treatment. OBJECTIVE: To determine the prevalence of bacterial strains and their antibiotic susceptibility in nosocomially acquired urinary tract infection in a university hospital between January and June 2003. METHODS: We analyzed the data of 188 patients with positive urine culture (= 10(5 colony-forming units/mL following a period of 48 hours after admission. RESULTS: Half of patients were male. Mean age was 50.26 ± 22.7 (SD, range 3 months to 88 years. Gram-negative bacteria were the agent in approximately 80% of cases. The most common pathogens were E. coli (26%, Klebsiella sp. (15%, P. aeruginosa (15% and Enterococcus sp. (11%. The overall bacteria susceptibility showed that the pathogens were more sensible to imipenem (83%, second or third generation cephalosporin and aminoglycosides; and were highly resistant to ampicillin (27% and cefalothin (30%. It is important to note the low susceptibility to ciprofloxacin (42% and norfloxacin (43%. CONCLUSION: This study suggests that if one can not wait the results of urine culture, the best choices to begin empiric treatment are imipenem, second or third generation cephalosporin and aminoglycosides. Cefalothin and ampicillin are quite ineffective to treat these infections.

  1. The effects of vaccination and immunity on bacterial infection dynamics in vivo.

    Directory of Open Access Journals (Sweden)

    Chris Coward

    2014-09-01

    Full Text Available Salmonella enterica infections are a significant global health issue, and development of vaccines against these bacteria requires an improved understanding of how vaccination affects the growth and spread of the bacteria within the host. We have combined in vivo tracking of molecularly tagged bacterial subpopulations with mathematical modelling to gain a novel insight into how different classes of vaccines and branches of the immune response protect against secondary Salmonella enterica infections of the mouse. We have found that a live Salmonella vaccine significantly reduced bacteraemia during a secondary challenge and restrained inter-organ spread of the bacteria in the systemic organs. Further, fitting mechanistic models to the data indicated that live vaccine immunisation enhanced both the bacterial killing in the very early stages of the infection and bacteriostatic control over the first day post-challenge. T-cell immunity induced by this vaccine is not necessary for the enhanced bacteriostasis but is required for subsequent bactericidal clearance of Salmonella in the blood and tissues. Conversely, a non-living vaccine while able to enhance initial blood clearance and killing of virulent secondary challenge bacteria, was unable to alter the subsequent bacterial growth rate in the systemic organs, did not prevent the resurgence of extensive bacteraemia and failed to control the spread of the bacteria in the body.

  2. Bacterial Infection Complicating Varicella Infection: A 10-Year Review of Hospitalized Children

    Directory of Open Access Journals (Sweden)

    Golda Milo-Manson

    1993-01-01

    Full Text Available An increased incidence of Streptococci pyogenes (group A streptococcus [GAS] infections and rheumatic fever has been reported over the past decade. The present study was conducted to determine whether a similar increase in such infections was observed after varicella, an infection previously shown to be associated with a high incidence of streptococcal infections. The charts of all children admitted with chickenpox to the Hospital for Sick Children in Toronto, Ontario from January 1, 1980 to December 31, 1989 were reviewed. Immunocompromised children and those hospitalized for another reason who had an incidental diagnosis of chickenpox were excluded. Twenty-five cases with bacterial infection complicating chickenpox were compared with 103 patients without secondary infection. No statistically significant differences were observed for age, gender, duration of illness prior to hospitalization or duration of hospitalization in the two groups. GAS was the most frequent isolate in the cases, followed by Staphylococcus aureus, Escherichia coli and Haemophilus influenzae. The types of infection were significantly different for GAS compared with other organisms, with a predominance of skin infections in the former group (χ2 analysis, P<0.05. No increase in the incidence of GAS infections was observed over time. This study confirms the importance of GAS infections in patients with varicella, but no increase was observed in hospitalized children during the 10-year study period.

  3. Piperine metabolically regulates peritoneal resident macrophages to potentiate their functions against bacterial infection.

    Science.gov (United States)

    Pan, Hao; Xu, Li-Hui; Huang, Mei-Yun; Zha, Qing-Bing; Zhao, Gao-Xiang; Hou, Xiao-Feng; Shi, Zi-Jian; Lin, Qiu-Ru; Ouyang, Dong-Yun; He, Xian-Hui

    2015-10-20

    Pepper, a daily-used seasoning for promoting appetite, is widely used in folk medicine for treating gastrointestinal diseases. Piperine is the major alkaloid in pepper and possesses a wide range of pharmacological activities. However, the mechanism for linking metabolic and medicinal activities of piperine remains unknown. Here we report that piperine robustly boosts mTORC1 activity by recruiting more system L1 amino acid transporter (SLC7A5/SLC3A2) to the cell membrane, thus promoting amino acid metabolism. Piperine-induced increase of mTORC1 activity in resident peritoneal macrophages (pMΦs) is correlated with enhanced production of IL-6 and TNF-α upon LPS stimulation. Such an enhancement of cytokine production could be abrogated by inhibitors of the mTOR signaling pathway, indicating mTOR's action in this process. Moreover, piperine treatment protected resident pMΦs from bacterium-induced apoptosis and disappearance, and increased their bacterial phagocytic ability. Consequently, piperine administration conferred mice resistance against bacterial infection and even sepsis. Our data highlight that piperine has the capacity to metabolically reprogram peritoneal resident macrophages to fortify their innate functions against bacterial infection.

  4. The burden of invasive bacterial infections in Pemba, Zanzibar.

    Directory of Open Access Journals (Sweden)

    Kamala Thriemer

    Full Text Available BACKGROUND: We conducted a surveillance study to determine the leading causes of bloodstream infection in febrile patients seeking treatment at three district hospitals in Pemba Island, Zanzibar, Tanzania, an area with low malaria transmission. METHODS: All patients above two months of age presenting to hospital with fever were screened, and blood was collected for microbiologic culture and malaria testing. Bacterial sepsis and malaria crude incidence rates were calculated for a one-year period and were adjusted for study participation and diagnostic sensitivity of blood culture. RESULTS: Blood culture was performed on 2,209 patients. Among them, 166 (8% samples yielded bacterial growth; 87 (4% were considered as likely contaminants; and 79 (4% as pathogenic bacteria. The most frequent pathogenic bacteria isolated were Salmonella Typhi (n = 46; 58%, followed by Streptococcus pneumoniae (n = 12; 15%. The crude bacteremia rate was 6/100,000 but when adjusted for potentially missed cases the rate may be as high as 163/100,000. Crude and adjusted rates for S. Typhi infections and malaria were 4 and 110/100,000 and 4 and 47/100,000, respectively. Twenty three (51%, 22 (49% and 22 (49% of the S. Typhi isolates were found to be resistant toward ampicillin, chloramphenicol and cotrimoxazole, respectively. Multidrug resistance (MDR against the three antimicrobials was detected in 42% of the isolates. CONCLUSIONS: In the presence of very low malaria incidence we found high rates of S. Typhi and S. pneumoniae infections on Pemba Island, Zanzibar. Preventive measures such as vaccination could reduce the febrile disease burden.

  5. Unveiling ubiquitinome rearrangements induced by Salmonella infection.

    Science.gov (United States)

    Bionda, Tihana; Behrends, Christian

    2016-09-01

    Ubiquitination plays a critical role in the activation of host immune responses to infection and serves as a signal for pathogen delivery to phagophores along the xenophagy pathway. We recently performed systematic ubiquitination site profiling of epithelial cells infected with Salmonella Typhimurium. Our findings specifically highlight components of the NFKB, membrane trafficking pathways and RHO GTPase systems as ubiquitination hubs during infection. In addition, a broad spectrum of bacterial effectors and several outer membrane proteins are ubiquitinated in infected cells. This comprehensive resource of ubiquitinome dynamics during Salmonella infection enables further understanding of the complex host-pathogen interplay and may reveal novel targets for the inhibition of Salmonella invasion and inflammation.

  6. Photodynamic therapy can induce a protective innate immune response against murine bacterial arthritis via neutrophil accumulation.

    Directory of Open Access Journals (Sweden)

    Masamitsu Tanaka

    Full Text Available BACKGROUND: Local microbial infections induced by multiple-drug-resistant bacteria in the orthopedic field can be intractable, therefore development of new therapeutic modalities is needed. Photodynamic therapy (PDT is a promising alternative modality to antibiotics for intractable microbial infections, and we recently reported that PDT has the potential to accumulate neutrophils into the infected site which leads to resolution of the infection. PDT for cancer has long been known to be able to stimulate the innate and adaptive arms of the immune system. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, a murine methicillin-resistant Staphylococcus aureus (MRSA arthritis model using bioluminescent MRSA and polystyrene microparticles was established, and both the therapeutic (Th-PDT and preventive (Pre-PDT effects of PDT using methylene blue as photosensitizer were examined. Although Th-PDT could not demonstrate direct bacterial killing, neutrophils were accumulated into the infectious joint space after PDT and MRSA arthritis was reduced. With the preconditioning Pre-PDT regimen, neutrophils were quickly accumulated into the joint immediately after bacterial inoculation and bacterial growth was suppressed and the establishment of infection was inhibited. CONCLUSIONS/SIGNIFICANCE: This is the first demonstration of a protective innate immune response against a bacterial pathogen produced by PDT.

  7. BACTERIAL INFECTIONS FOLLOWING SPLENECTOMY FOR MALIGNANT AND NONMALIGNANT HEMATOLOGIC DISEASES

    Directory of Open Access Journals (Sweden)

    Giuseppe Leone

    2015-10-01

    Full Text Available Splenectomy, while often necessary in otherwise healthy patients after major trauma, find its primary indication for patients with an underlying malignant or nonmalignant hematologic diseases. Indications of splenectomy for hematologic diseases have been reducing in the last few years, due to improved diagnostic and therapeutic tools. In high-income countries, there is a clear decrease over calendar time in the incidence of all indication splenectomy except nonmalignant hematologic diseases. However, splenectomy, even if with different modalities including laparoscopic splenectomy and partial splenectomy, continue to be a current surgical practice both in nonmalignant hematologic diseases, such as Immune Thrombocytopenic Purpura (ITP, Autoimmune Hemolytic Anemia (AIHA, Congenital Hemolytic Anemia such as Spherocytosis, Sickle Cell Anemia and Thalassemia and Malignant Hematological Disease, such as lymphoma. Today millions of people in the world are splenectomized. Splenectomy, independently of its cause, induces an early and late increase in the incidence of venous thromboembolism and infections. Infections remain the most dangerous complication of splenectomy. After splenectomy, the levels of antibody are preserved but there is a loss of memory B cells against pneumococcus and tetanus, and the loss of marginal zone monocytes deputed to immunological defense from capsulated bacteria. Commonly, the infections strictly correlated to the absence of the spleen or a decreased or absent splenic function are due to encapsulated bacteria that are the most virulent pathogens in this set of patients. Vaccination with polysaccharide and conjugate vaccines again Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis should be performed before the splenectomy. This practice reduces but does not eliminate the occurrence of overwhelming infections due to capsulated bacteria. At present, most of infection found in splenectomized patients

  8. Antimicrobial Nanoparticle for the Treatment of Bacterial Infection

    Science.gov (United States)

    Pornpattananangkul, Dissaya

    Liposomes are spherical lipid vesicles with bilayered membrane structure, which have been recognized as one of the most widely used carriers for delivering a myriad of pharmaceuticals. Liposomes can carry both hydrophilic and hydrophobic agents with high efficiency and protect them from undesired effects of external conditions. However, the applications of liposomes are usually limited by their instability during storage. They are inclined to fuse with one another immediately after preparation, resulting in undesired mixing, increase in size, and payload loss. To overcome this limitation, this dissertation will focus on the technology to stabilize liposomes during storage and destabilize at specific conditions in order to allow controllable therapeutic release, as well as demonstrate their application to treat one of the bacterial infection diseases, acne vulgaris. The first area of this research is stimuli-responsive liposomes development, where the liposomes are stabilized by introducing gold nanoparticles to adsorb to their surface. As a result, the liposomes are prevented from fusing with one another and undesirable payload release during storage or physiological environments. Moreover, therapeutic is controllably released depending on environment conditions, such as acidic pH and bacterial virulence factor. In case of acid-responsive liposomes, the bound gold nanoparticles can effectively prevent liposomes from fusing with one another at neutral pH value, while at acidic environment (e.g. pHtoxin. When nanoparticle-stabilized liposomes encounter with bacteria that secrete toxin, the toxin will insert into the liposome membranes and form pores, through which the encapsulated therapeutic agents are released. The released drugs subsequently impose antimicrobial effects on the toxin-secreting bacteria. It was observed that in the presence of toxin-secreting bacteria, 100% of the encapsulated antibiotics were released from the gold nanoparticle-stabilized liposomes

  9. Towards rational treatment of bacterial infections during extended space travel.

    Science.gov (United States)

    Taylor, Peter W; Sommer, Andrei P

    2005-09-01

    In the next 15-30 years, manned space flight to Mars, our planetary neighbour, will become a reality and astronauts are likely to spend at least 2-3 years away from Earth. Time spent in such extreme environments will result in a diminution of immune status and profound changes in the human bacterial microflora. In microgravity, the efficacy of antibiotics is reduced and microbial mutation rates increase dramatically. These factors will impinge on the capacity to treat effectively the infections that will doubtless arise during such long and stressful endeavour. We highlight new rationales for the treatment of infectious disease that may be applicable to therapy in extreme environments such as deep space.

  10. Bacterial infection in an Irrawaddy dolphin (Orcaella brevirostris).

    Science.gov (United States)

    Yu, Jin Hai; Xia, Zhao Fei

    2013-03-01

    One pregnant captive Irrawaddy dolphin (Orcaella brevirostris), with a body length of 225 cm, was found dead on 8 June 2009. The dolphin was anorexic and circling at the bottom of the pool before death. Laboratory tests revealed an increased leukocyte count and decreased platelet count; increased erythrocyte sedimentation rate; and slightly decreased red blood cell count, hemoglobin, and hematocrit. Alkaline phosphatase, creatinine, and glucose were significantly decreased. Moreover, uric acid and alanine aminotransferase and aspartate aminotransferase levels were elevated. A 57-cm fetus was recovered. The respiratory system, intestinal mucosa, mesentery and mesenteric lymph nodes, and spleen were congested and hemorrhagic. The heart, liver, and kidney appeared normal. Klebsiella spp. and Staphylococcus aureus were identified in the amniotic fluid. This is the first case report of bacterial infection in an Irrawaddy dolphin.

  11. Infection-related hemolysis and susceptibility to Gram-negative bacterial co-infection

    Directory of Open Access Journals (Sweden)

    Katharine eOrf

    2015-06-01

    Full Text Available Increased susceptibility to co-infection with enteric Gram-negative bacteria, particularly non-typhoidal Salmonella, is reported in malaria and Oroya fever (Bartonella bacilliformis infection, and can lead to increased mortality. Accumulating epidemiological evidence indicates a causal association with risk of bacterial co-infection, rather than just co-incidence of common risk factors. Both malaria and Oroya fever are characterised by hemolysis, and observations in humans and animal models suggest that hemolysis causes the susceptibility to bacterial co-infection. Evidence from animal models implicates hemolysis in the impairment of a variety of host defence mechanisms, including macrophage dysfunction, neutrophil dysfunction and impairment of adaptive immune responses. One mechanism supported by evidence from animal models and human data, is the induction of heme oxygenase-1 in bone marrow, which impairs the ability of developing neutrophils to mount a competent oxidative burst. As a result, dysfunctional neutrophils become a new niche for replication of intracellular bacteria. Here we critically appraise and summarize the key evidence for mechanisms which may contribute to these very specific combinations of co-infections, and propose interventions to ameliorate this risk.

  12. Preventing infective complications relating to induced abortion.

    Science.gov (United States)

    Mary, Nirmala; Mahmood, Tahir A

    2010-08-01

    Infective complications following induced abortions are still a common cause of morbidity and mortality. This review focusses on defining the strategies to improve care of women seeking an induced abortion and to reduce infective complications. We have considered the evidence for screening and cost-effectiveness for antibiotic prophylaxis. Current evidence suggests that treating all women with prophylactic antibiotics in preference to screening and treating is the most cost-effective way of reducing infective complications following induced abortions. The final strategy to prevent infective complications should be individualized for each region/area depending on the prevalence of organisms causing pelvic infections and the resources available.

  13. Clinical indicators for bacterial co-infection in Ghanaian children with P. falciparum infection.

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    Maja Verena Nielsen

    Full Text Available Differentiation of infectious causes in severely ill children is essential but challenging in sub- Saharan Africa. The aim of the study was to determine clinical indicators that are able to identify bacterial co-infections in P. falciparum infected children in rural Ghana. In total, 1,915 severely ill children below the age of 15 years were recruited at Agogo Presbyterian Hospital in Ghana between May 2007 and February 2011. In 771 (40% of the children malaria parasites were detected. This group was analyzed for indicators of bacterial co-infections using bivariate and multivariate regression analyses with 24 socio-economic variables, 16 terms describing medical history and anthropometrical information and 68 variables describing clinical symptoms. The variables were tested for sensitivity, specificity, positive predictive value and negative predictive value. In 46 (6.0% of the children with malaria infection, bacterial co-infection was detected. The most frequent pathogens were non-typhoid salmonellae (45.7%, followed by Streptococcus spp. (13.0%. Coughing, dehydration, splenomegaly, severe anemia and leukocytosis were positively associated with bacteremia. Domestic hygiene and exclusive breastfeeding is negatively associated with bacteremia. In cases of high parasitemia (>10,000/μl, a significant association with bacteremia was found for splenomegaly (OR 8.8; CI 1.6-48.9, dehydration (OR 18.2; CI 2.0-166.0 and coughing (OR 9.0; CI 0.7-118.6. In children with low parasitemia, associations with bacteremia were found for vomiting (OR 4.7; CI 1.4-15.8, severe anemia (OR 3.3; CI 1.0-11.1 and leukocytosis (OR 6.8 CI 1.9-24.2. Clinical signs of impaired microcirculation were negatively associated with bacteremia. Ceftriaxone achieved best coverage of isolated pathogens. The results demonstrate the limitation of clinical symptoms to determine bacterial co-infections in P. falciparum infected children. Best clinical indicators are dependent on the

  14. The Nuclear Receptor LXR Limits Bacterial Infection of Host Macrophages through a Mechanism that Impacts Cellular NAD Metabolism

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    Jonathan Matalonga

    2017-01-01

    Full Text Available Macrophages exert potent effector functions against invading microorganisms but constitute, paradoxically, a preferential niche for many bacterial strains to replicate. Using a model of infection by Salmonella Typhimurium, we have identified a molecular mechanism regulated by the nuclear receptor LXR that limits infection of host macrophages through transcriptional activation of the multifunctional enzyme CD38. LXR agonists reduced the intracellular levels of NAD+ in a CD38-dependent manner, counteracting pathogen-induced changes in macrophage morphology and the distribution of the F-actin cytoskeleton and reducing the capability of non-opsonized Salmonella to infect macrophages. Remarkably, pharmacological treatment with an LXR agonist ameliorated clinical signs associated with Salmonella infection in vivo, and these effects were dependent on CD38 expression in bone-marrow-derived cells. Altogether, this work reveals an unappreciated role for CD38 in bacterial-host cell interaction that can be pharmacologically exploited by activation of the LXR pathway.

  15. In Vivo Evaluation of Bacterial Infection Involving Morphologically Different Surgical Meshes

    NARCIS (Netherlands)

    Engelsman, Anton F.; van Dam, Gooitzen M.; van der Mei, Henny C.; Busscher, Henk J.; Ploeg, Rutger J.

    2010-01-01

    Objective: To study the influence of morphology of surgical meshes on the course of bacterial infection under the influence of the host immune system in an in vivo chronic bacterial infection model. Background: The use of prosthetic meshes has increased dramatically the last decades in abdominal wal

  16. Severe bacterial non-aids infections in HIV-positive persons

    DEFF Research Database (Denmark)

    Søgaard, O S; Reekie, J; Ristola, M;

    2013-01-01

    This study aimed to determine incidence rates (IR) and identify risk factors for severe bacterial non-AIDS infections (SBnAI) requiring hospital admission.......This study aimed to determine incidence rates (IR) and identify risk factors for severe bacterial non-AIDS infections (SBnAI) requiring hospital admission....

  17. Bacterial lipopolysaccharide induces apoptosis in the trout ovary

    Directory of Open Access Journals (Sweden)

    Krasnov Aleksei

    2006-08-01

    Full Text Available Abstract Background In mammals it is well known that infections can lead to alterations in reproductive function. As part of the innate immune response, a number of cytokines and other immune factors is produced during bacterial infection or after treatment with lipopolysaccharide (LPS and acts on the reproductive system. In fish, LPS can also induce an innate immune response but little is known about the activation of the immune system by LPS on reproduction in fish. Therefore, we conducted studies to examine the in vivo and in vitro effects of lipopolysaccharide (LPS on the reproductive function of sexually mature female trout. Methods In saline- and LPS -injected brook trout, we measured the concentration of plasma steroids as well as the in vitro steroidogenic response (testosterone and 17alpha-hydroxyprogesterone of ovarian follicles to luteinizing hormone (LH, the ability of 17alpha,20beta-dihydroxy-4-pregnen-3-one to induce germinal vesicle breakdown (GVBD in vitro, and that of epinephrine to stimulate follicular contraction in vitro. We also examined the direct effects of LPS in vitro on steroid production, GVBD and contraction in brook trout ovarian follicles. The incidence of apoptosis was evaluated by TUNEL analysis. Furthermore, we examined the gene expression pattern in the ovary of saline- and LPS-injected rainbow trout by microarray analysis. Results LPS treatment in vivo did not affect plasma testosterone concentration or the basal in vitro production of steroids, although a small but significant potentiation of the effects of LH on testosterone production in vitro was observed in ovarian follicles from LPS-treated fish. In addition, LPS increased the plasma concentration of cortisol. LPS treatment in vitro did not affect the basal or LH-stimulated steroid production in brook trout ovarian follicles. In addition, we did not observe any effects of LPS in vivo or in vitro on GVBD or follicular contraction. Therefore, LPS did not

  18. Antibiotic resistance in prevalent bacterial and protozoan sexually transmitted infections

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    Karl Krupp

    2015-01-01

    Full Text Available The emergence of multi-drug resistant sexually transmitted infections (STIs is causing a treatment crisis across the globe. While cephalosporin-resistant gonorrhea is one of the most pressing issues, extensively antibiotic resistant Chlamydia trachomatis and Mycoplasma hominis are also becoming commonplace. Experts have suggested that the failure of current treatment regimens are "largely inevitable" and have called for entirely new classes of antimicrobial agents. With the exception of several new classes of drugs primarily targeting nosocomial infections, progress has been slow. While pharmaceutical companies continue to introduce new drugs, they are based on decade-old discoveries. While there is disagreement about what constitutes new classes of antibiotics, many experts suggest that the last truly new family of antimicrobials was discovered in 1987. This review summarizes the existing literature on antibiotic resistance in common bacterial and protozoal STIs. It also briefly discusses several of the most promising alternatives to current therapies, and further examines how advances in drug delivery, formulation, concentration, and timing are improving the efficacy of existing treatments. Finally, the paper discusses the current state of pharmaceutical development for multidrug-resistant STI.

  19. Photorhabdus luminescens genes induced upon insect infection

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    Jung Kirsten

    2008-05-01

    Full Text Available Abstract Background Photorhabdus luminescens is a Gram-negative luminescent enterobacterium and a symbiote to soil nematodes belonging to the species Heterorhabditis bacteriophora. P.luminescens is simultaneously highly pathogenic to insects. This bacterium exhibits a complex life cycle, including one symbiotic stage characterized by colonization of the upper nematode gut, and a pathogenic stage, characterized by release from the nematode into the hemocoel of insect larvae, resulting in rapid insect death caused by bacterial toxins. P. luminescens appears to sense and adapt to the novel host environment upon changing hosts, which facilitates the production of factors involved in survival within the host, host-killing, and -exploitation. Results A differential fluorescence induction (DFI approach was applied to identify genes that are up-regulated in the bacterium after infection of the insect host Galleria mellonella. For this purpose, a P. luminescens promoter-trap library utilizing the mCherry fluorophore as a reporter was constructed, and approximately 13,000 clones were screened for fluorescence induction in the presence of a G. mellonella larvae homogenate. Since P. luminescens has a variety of regulators that potentially sense chemical molecules, like hormones, the screen for up-regulated genes or operons was performed in vitro, excluding physicochemical signals like oxygen, temperature or osmolarity as variables. Clones (18 were obtained exhibiting at least 2.5-fold induced fluorescence and regarded as specific responders to insect homogenate. In combination with a bioinformatics approach, sequence motifs were identified in these DNA-fragments that are similar to 29 different promoters within the P. luminescens genome. By cloning each of the predicted promoters upstream of the reporter gene, induction was verified for 27 promoters in vitro, and for 24 promoters in viable G. mellonella larvae. Among the validated promoters are some known

  20. The host type Ⅰ interferon response to viral and bacterial infections

    Institute of Scientific and Technical Information of China (English)

    Andrea K. PERRY; Gang CHEN; Dahai ZHENG; Hong TANG; Genhong CHENG

    2005-01-01

    Type Ⅰ interferons (IFN) are well studied cytokines with anti-viral and immune-modulating functions. Type Ⅰ IFNs are produced following viral infections, but until recently, the mechanisms of viral recognition leading to IFN production were largely unknown. Toll like receptors (TLRs) have emerged as key transducers of type Ⅰ IFN during viral infections by recognizing various viral components. Furthermore, much progress has been made in defining the signaling pathways downstream of TLRs for type Ⅰ IFN production. TLR7 and TLR9 have become apparent as universally important in inducing type Ⅰ IFN during infection with most viruses, particularly by plasmacytoid dendritic cells. New intracellular viral pattern recognition receptors leading to type Ⅰ IFN production have been identified. Many bacteria can also induce the up-regulation of these cytokines. Interestingly, recent studies have found a detrimental effect on host cells if type Ⅰ IFN is produced during infection with the intracellular gram-positive bacterial pathogen, Listeria monocytogenes. This review will discuss the recent advances made in defining the signaling pathways leading to type Ⅰ IFN production.

  1. An overview of the role of bacterial infection in male infertility

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    Hamed Fanaei

    2013-03-01

    Full Text Available An important cause of male infertility is the bacterial infections of the genitourinary tract. These infections affect sperm cell function and whole spermatogenesis and also cause deterioration in spermatogenesis, obstruction of the seminal tract, and impairment of spermatozoa function. The most important bacteria associated with genitourinary tract infections include chlamydia trachomatis, Neisseria gonorrhoeae, and genital mycoplasma species. Inappropriate or delayed therapy of the bacterial infections of the genitourinary tract will lead to reduced fertility and, subsequently in severe cases, infertility. In other words, a good understanding of the interaction between bacterial infections and the reproductive system plays an important role in the treatment of infertile men. In this review article, we will discuss clinical and laboratory findings related to the bacterial infection of the genitourinary tract and its effects on male infertility.

  2. Comparison on Serum Levels of Procalcitonin of Children with Viral and Bacterial Infection

    Institute of Scientific and Technical Information of China (English)

    2013-01-01

    Objective To compare and analyze serum levels of procalcitonin (PCT) of children with viral and bacterial infection and probe into the importance of determining the level of serum PCT in the diagnosis of bacterial infection in order to provide evidences of the clinical use of antibiotics. Methods A total of 85 cases of children with an average age of 8.9 years (10 months-12 years) were enrolled in this study, 53 cases were with viral infection and 32 cases with bacterial infection. We determined serum levels of PCT by semi-quantitative solid phase immunoassay, and the serum levels of PCT were divided into four grades as Results The serum level of PCT of the group with bacterial infection were signiifcantly higher than that of the group with viral infection (P Conclusions Serum PCT is a bacterial sensitive marker of bacterial infection in children, and the determination of the level of serum PCT is helpful for the diagnosis of bacterial infection, which can also be a basis for the use of antibiotics.

  3. Ischemic stroke induces gut permeability and enhances bacterial translocation leading to sepsis in aged mice

    Science.gov (United States)

    Verma, Rajkumar; Venna, Venugopal R.; Liu, Fudong; Chauhan, Anjali; Koellhoffer, Edward; Patel, Anita; Ricker, Austin; Maas, Kendra; Graf, Joerg; McCullough, Louise D.

    2016-01-01

    Aging is an important risk factor for post-stroke infection, which accounts for a large proportion of stroke-associated mortality. Despite this, studies evaluating post-stroke infection rates in aged animal models are limited. In addition, few studies have assessed gut microbes as a potential source of infection following stroke. Therefore we investigated the effects of age and the role of bacterial translocation from the gut in post-stroke infection in young (8-12 weeks) and aged (18-20 months) C57Bl/6 male mice following transient middle cerebral artery occlusion (MCAO) or sham surgery. Gut permeability was examined and peripheral organs were assessed for the presence of gut-derived bacteria following stroke. Furthermore, sickness parameters and components of innate and adaptive immunity were examined. We found that while stroke induced gut permeability and bacterial translocation in both young and aged mice, only young mice were able to resolve infection. Bacterial species seeding peripheral organs also differed between young (Escherichia) and aged (Enterobacter) mice. Consequently, aged mice developed a septic response marked by persistent and exacerbated hypothermia, weight loss, and immune dysfunction compared to young mice following stroke. PMID:27115295

  4. Long-term impact of systemic bacterial infection on the cerebral vasculature and microglia

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    Püntener Ursula

    2012-06-01

    Full Text Available Abstract Background Systemic infection leads to generation of inflammatory mediators that result in metabolic and behavioural changes. Repeated or chronic systemic inflammation leads to a state of innate immune tolerance: a protective mechanism against overactivity of the immune system. In this study, we investigated the immune adaptation of microglia and brain vascular endothelial cells in response to systemic inflammation or bacterial infection. Methods Mice were given repeated doses of lipopolysaccharide (LPS or a single injection of live Salmonella typhimurium. Inflammatory cytokines were measured in serum, spleen and brain, and microglial phenotype studied by immunohistochemistry. To assess priming of the innate immune response in the brain, mice were infected with Salmonella typhimurium and subsequently challenged with a focal unilateral intracerebral injection of LPS. Results Repeated systemic LPS challenges resulted in increased brain IL-1β, TNF-α and IL-12 levels, despite attenuated systemic cytokine production. Each LPS challenge induced significant changes in burrowing behaviour. In contrast, brain IL-1β and IL-12 levels in Salmonella typhimurium-infected mice increased over three weeks, with high interferon-γ levels in the circulation. Behavioural changes were only observed during the acute phase of the infection. Microglia and cerebral vasculature display an activated phenotype, and focal intracerebral injection of LPS four weeks after infection results in an exaggerated local inflammatory response when compared to non-infected mice. Conclusions These studies reveal that the innate immune cells in the brain do not become tolerant to systemic infection, but are primed instead. This may lead to prolonged and damaging cytokine production that may have a profound effect on the onset and/or progression of pre-existing neurodegenerative disease.

  5. Dissolution of infection-induced struvite bladder stones by using a noncalculolytic diet and antibiotic therapy.

    Science.gov (United States)

    Rinkardt, Nancy E; Houston, Doreen M

    2004-10-01

    An 8-year-old, female spayed miniature schnauzer was presented for pollakiuria and gross hematuria. Infection-induced struvite urolithiasis with concurrent bacterial urinary tract infection was diagnosed. The treatment is described, followed by a brief discussion of struvite stones and their medical management.

  6. Dissolution of infection-induced struvite bladder stones by using a noncalculolytic diet and antibiotic therapy

    OpenAIRE

    Rinkardt, Nancy E.; Houston, Doreen M.

    2004-01-01

    An 8-year-old, female spayed miniature schnauzer was presented for pollakiuria and gross hematuria. Infection-induced struvite urolithiasis with concurrent bacterial urinary tract infection was diagnosed. The treatment is described, followed by a brief discussion of struvite stones and their medical management.

  7. Multiresistant bacterial infections in liver cirrhosis: Clinical impact and new empirical antibiotic treatment policies

    Science.gov (United States)

    Acevedo, Juan

    2015-01-01

    Recently, important changes have been reported regarding the epidemiology of bacterial infections in liver cirrhosis. There is an emergence of multiresistant bacteria in many European countries and also worldwide, including the United States and South Korea. The classic empirical antibiotic treatment (third-generation cephalosporins, e.g., ceftriaxone, cefotaxime or amoxicillin-clavulanic acid) is still effective in infections acquired in the community, but its failure rate in hospital acquired infections and in some health-care associated infections is high enough to ban its use in these settings. The current editorial focuses on the different epidemiology of bacterial infections in cirrhosis across countries and on its therapeutic implications. PMID:25954474

  8. Piperine Suppresses Pyroptosis and Interleukin-1β Release upon ATP Triggering and Bacterial Infection

    Science.gov (United States)

    Liang, Yi-Dan; Bai, Wen-Jing; Li, Chen-Guang; Xu, Li-Hui; Wei, Hong-Xia; Pan, Hao; He, Xian-Hui; Ouyang, Dong-Yun

    2016-01-01

    Piperine is a phytochemical present in black pepper (Piper nigrum Linn) and other related herbs, possessing a wide array of pharmacological activities including anti-inflammatory effects. Previously, we demonstrated that piperine has therapeutic effects on bacterial sepsis in mice, but the underlying mechanism has not been fully elucidated. In this study, we aimed to investigate the influences of piperine on pyroptosis in murine macrophages. The results showed that piperine dose-dependently inhibited ATP-induced pyroptosis, thereby suppressing interleukin-1β (IL-1β) or high mobility group box-1 protein (HMGB1) release in LPS-primed bone marrow-derived macrophages and J774A.1 cells. Accompanying this, ATP-induced AMP-activated protein kinase (AMPK) activation was greatly suppressed by piperine, whereas AMPK agonist metformin counteracted piperine’s inhibitory effects on pyroptosis. Moreover, piperine administration greatly reduced both peritoneal and serum IL-1β levels in the mouse model intraperitoneally infected with Escherichia coli, suggestive of suppressing systemic inflammation and pyroptosis. Our data indicated that piperine could protect macrophages from pyroptosis and reduced IL-1β and HMGB1 release by suppressing ATP-induced AMPK activation, suggesting that piperine may become a potential therapeutic agent against bacterial sepsis. PMID:27812336

  9. Piperine suppresses pyroptosis and interleukin-1β release upon ATP triggering and bacterial infection

    Directory of Open Access Journals (Sweden)

    Yi-Dan Liang

    2016-10-01

    Full Text Available Piperine is a phytochemical present in black pepper (Piper nigrum Linn and other related herbs, possessing a wide array of pharmacological activities including anti-inflammatory effects. Previously, we demonstrated that piperine has therapeutic effects on bacterial sepsis in mice, but the underlying mechanism has not been fully elucidated. In this study, we aimed to investigate the influences of piperine on pyroptosis in murine macrophages. The results showed that piperine dose-dependently inhibited ATP-induced pyroptosis, thereby suppressing interleukin-1β (IL-1β or high mobility group box-1 protein (HMGB1 release in LPS-primed bone marrow-derived macrophages (BMDMs and J774A.1 cells. Accompanying this, ATP-induced AMP-activated protein kinase (AMPK activation was greatly suppressed by piperine, whereas AMPK agonist metformin counteracted piperine’s inhibitory effects on pyroptosis. Moreover, piperine administration greatly reduced both peritoneal and serum IL-1β levels in the mouse model intraperitoneally infected with Escherichia coli, suggestive of suppressing systemic inflammation and pyroptosis. Our data indicated that piperine could protect macrophages from pyroptosis and reduced IL-1β and HMGB1 release by suppressing ATP-induced AMPK activation, suggesting that piperine may become a potential therapeutic agent against bacterial sepsis.

  10. Influenza virus induces bacterial and nonbacterial otitis media.

    Science.gov (United States)

    Short, Kirsty R; Diavatopoulos, Dimitri A; Thornton, Ruth; Pedersen, John; Strugnell, Richard A; Wise, Andrew K; Reading, Patrick C; Wijburg, Odilia L

    2011-12-15

    Otitis media (OM) is one of the most common childhood diseases. OM can arise when a viral infection enables bacteria to disseminate from the nasopharynx to the middle ear. Here, we provide the first infant murine model for disease. Mice coinfected with Streptococcus pneumoniae and influenza virus had high bacterial load in the middle ear, middle ear inflammation, and hearing loss. In contrast, mice colonized with S. pneumoniae alone had significantly less bacteria in the ear, minimal hearing loss, and no inflammation. Of interest, infection with influenza virus alone also caused some middle ear inflammation and hearing loss. Overall, this study provides a clinically relevant and easily accessible animal model to study the pathogenesis and prevention of OM. Moreover, we provide, to our knowledge, the first evidence that influenza virus alone causes middle ear inflammation in infant mice. This inflammation may then play an important role in the development of bacterial OM.

  11. Cytokines and Chemokines as Biomarkers of Community-Acquired Bacterial Infection

    Directory of Open Access Journals (Sweden)

    Michal Holub

    2013-01-01

    Full Text Available Routinely used biomarkers of bacterial etiology of infection, such as C-reactive protein and procalcitonin, have limited usefulness for evaluation of infections since their expression is enhanced by a number of different conditions. Therefore, several inflammatory cytokines and chemokines were analyzed with sera from patients hospitalized for moderate bacterial and viral infectious diseases. In total, 57 subjects were enrolled: 21 patients with community-acquired bacterial infections, 26 patients with viral infections, and 10 healthy subjects (control cohorts. The laboratory analyses were performed using Luminex technology, and the following molecules were examined: IL-1Ra, IL-2, IL-4, IL-6, IL-8, TNF-α, INF-γ, MIP-1β, and MCP-1. Bacterial etiology of infection was associated with significantly (P<0.001 elevated serum concentrations of IL-1Ra, IL-2, IL-6, and TNF-α in comparison to levels observed in the sera of patients with viral infections. In the patients with bacterial infections, IL-1Ra and IL-8 demonstrated positive correlation with C-reactive protein, whereas, IL-1Ra, TNF-α, and MCP-1 correlated with procalcitonin. Furthermore, elevated levels of IL-1Ra, IL-6, and TNF-α decreased within 3 days of antibiotic therapy to levels observed in control subjects. The results show IL-1Ra as a potential useful biomarker of community-acquired bacterial infection.

  12. Mathematical Modeling of the Induced Mutation Process in Bacterial Cells

    Science.gov (United States)

    Belov, Oleg V.; Krasavin, Evgeny A.; Parkhomenko, Alexander Yu.

    2010-01-01

    A mathematical model of the ultraviolet (UV) irradiation-induced mutation process in bacterial cells Escherichia coli is developed. Using mathematical approaches, the whole chain of events is tracked from a cell exposure to the damaging factor to mutation formation in the DNA chain. An account of the key special features of the regulation of this genetic network allows predicting the effects induced by the cell exposure to certain UV energy fluence.

  13. Bacterial Biofilms and Catheters: A Key to Understanding Bacterial Strategies in Catheter-Associated Urinary Tract Infection

    Directory of Open Access Journals (Sweden)

    J Curtis Nickel

    1992-01-01

    Full Text Available Despite major technological improvements in catheter drainage systems, the indwelling Foley catheter remains the most common cause of nosocomial infection in medical practice. By approaching this common complicated urinary tract infection from the perspective of the biofilm strategy bacteria appear to use to overcome obstacles to produce bacteriuria, one appreciates a new understanding of these infections. An adherent biofilm of bacteria in their secretory products ascends the luminal and external surface of the catheter and drainage system from a contaminated drainage spigot or urethral meatus into the bladder. If the intraluminal route of bacterial ascent is delayed by strict sterile closed drainage or addition of internal modifications to the system, the extraluminal or urethral route assumes greater importance in the development of bacteriuria, but takes significantly longer. Bacterial growth within these thick coherent biofilms confers a large measure of relative resistance to antibiotics even though the individual bacterium remains sensitive, thus accounting for the failure of antibiotic therapy. With disruption of the protective mucous layer of the bladder by mechanical irritation, the bacteria colonizing the catheter can adhere to the bladder’s mucosal surface and cause infection. An appreciation of the role of bacterial biofilms in these infections should suggest future directions for research that may ultimately reduce the risk of catheter-associated infection.

  14. Prosthesis infections after orthopedic joint replacement: the possible role of bacterial biofilms

    Directory of Open Access Journals (Sweden)

    Zhijun Song

    2013-06-01

    Full Text Available Prosthesis-related infection is a serious complication for patients after orthopedic joint replacement, which is currently difficult to treat with antibiotic therapy. Consequently, in most cases, removal of the infected prosthesis is the only solution to cure the infection. It is, therefore, important to understand the comprehensive interaction between the microbiological situation and the host immune responses that lead to prosthesis infections. Evidence indicates that prosthesis infections are actually biofilm-correlated infections that are highly resistant to antibiotic treatment and the host immune responses. The authors reviewed the related literature in the context of their clinical experience, and discussed the possible etiology and mechanism leading to the infections, especially problems related to bacterial biofilm, and prophylaxis and treatment of infection, including both microbiological and surgical measures. Recent progress in research into bacterial biofilm and possible future treatment options of prosthesis-related infections are discussed.

  15. Unveiling ubiquitinome rearrangements induced by Salmonella infection

    Science.gov (United States)

    Bionda, Tihana; Behrends, Christian

    2016-01-01

    ABSTRACT Ubiquitination plays a critical role in the activation of host immune responses to infection and serves as a signal for pathogen delivery to phagophores along the xenophagy pathway. We recently performed systematic ubiquitination site profiling of epithelial cells infected with Salmonella Typhimurium. Our findings specifically highlight components of the NFKB, membrane trafficking pathways and RHO GTPase systems as ubiquitination hubs during infection. In addition, a broad spectrum of bacterial effectors and several outer membrane proteins are ubiquitinated in infected cells. This comprehensive resource of ubiquitinome dynamics during Salmonella infection enables further understanding of the complex host-pathogen interplay and may reveal novel targets for the inhibition of Salmonella invasion and inflammation. PMID:27467224

  16. Macrophage activation induced by Brucella DNA suppresses bacterial intracellular replication via enhancing NO production.

    Science.gov (United States)

    Liu, Ning; Wang, Lin; Sun, Changjiang; Yang, Li; Tang, Bin; Sun, Wanchun; Peng, Qisheng

    2015-12-01

    Brucella DNA can be sensed by TLR9 on endosomal membrane and by cytosolic AIM2-inflammasome to induce proinflammatory cytokine production that contributes to partially activate innate immunity. Additionally, Brucella DNA has been identified to be able to act as a major bacterial component to induce type I IFN. However, the role of Brucella DNA in Brucella intracellular growth remains unknown. Here, we showed that stimulation with Brucella DNA promote macrophage activation in TLR9-dependent manner. Activated macrophages can suppresses wild type Brucella intracellular replication at early stage of infection via enhancing NO production. We also reported that activated macrophage promotes bactericidal function of macrophages infected with VirB-deficient Brucella at the early or late stage of infection. This study uncovers a novel function of Brucella DNA, which can help us further elucidate the mechanism of Brucella intracellular survival.

  17. The balance of apoptotic and necrotic cell death in Mycobacterium tuberculosis infected macrophages is not dependent on bacterial virulence.

    OpenAIRE

    2012-01-01

    BACKGROUND: An important mechanism of Mycobacterium tuberculosis pathogenesis is the ability to control cell death pathways in infected macrophages: apoptotic cell death is bactericidal, whereas necrotic cell death may facilitate bacterial dissemination and transmission. METHODS: We examine M.tuberculosis control of spontaneous and chemically induced macrophage cell death using automated confocal fluorescence microscopy, image analysis, flow cytometry, plate-reader based vitality assays, and ...

  18. Roles of the host oxidative immune response and bacterial antioxidant rubrerythrin during Porphyromonas gingivalis infection.

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    Piotr Mydel

    2006-07-01

    Full Text Available The efficient clearance of microbes by neutrophils requires the concerted action of reactive oxygen species and microbicidal components within leukocyte secretory granules. Rubrerythrin (Rbr is a nonheme iron protein that protects many air-sensitive bacteria against oxidative stress. Using oxidative burst-knockout (NADPH oxidase-null mice and an rbr gene knockout bacterial strain, we investigated the interplay between the phagocytic oxidative burst of the host and the oxidative stress response of the anaerobic periodontal pathogen Porphyromonas gingivalis. Rbr ensured the proliferation of P. gingivalis in mice that possessed a fully functional oxidative burst response, but not in NADPH oxidase-null mice. Furthermore, the in vivo protection afforded by Rbr was not associated with the oxidative burst responses of isolated neutrophils in vitro. Although the phagocyte-derived oxidative burst response was largely ineffective against P. gingivalis infection, the corresponding oxidative response to the Rbr-positive microbe contributed to host-induced pathology via potent mobilization and systemic activation of neutrophils. It appeared that Rbr also provided protection against reactive nitrogen species, thereby ensuring the survival of P. gingivalis in the infected host. The presence of the rbr gene in P. gingivalis also led to greater oral bone loss upon infection. Collectively, these results indicate that the host oxidative burst paradoxically enhances the survival of P. gingivalis by exacerbating local and systemic inflammation, thereby contributing to the morbidity and mortality associated with infection.

  19. Chronic hyperosmotic stress inhibits renal Toll-Like Receptors expression in striped catfish (Pangasianodon hypophthalmus, Sauvage) exposed or not to bacterial infection.

    Science.gov (United States)

    Schmitz, Mélodie; Baekelandt, Sébastien; Bequet, Sandrine; Kestemont, Patrick

    2017-03-24

    Toll-like Receptors (TLRs) are the first innate receptors in recognizing pathogen-associated molecular patterns. In fish, upregulation of toll-like receptors during infection has been largely demonstrated while the effects of abiotic stressors on their expression remain poorly investigated. In this study, striped catfish were submitted during 20 days to three salinity profiles (freshwater, low saline water, saline water), followed by injection of a bacterial strain of Edwardsiella ictaluri. The expression of TLRs 1, 3, 4, 5, 7, 9, 19, 21, and 22 was measured in kidney at different time points in non infected and infected striped catfish. Infection induced overexpression of TLRs 1, 3, 4, 5, 7, 21 and 22. With elevated salinity, the expression of all TLRs, except TLR5, was severely decreased, particularly after bacterial infection. The TLRs responsiveness of striped catfish facing bacterial disease and salinity stress and possible consequences on striped catfish immune response's efficiency are discussed.

  20. Virus Infection-Induced Bronchial Asthma Exacerbation

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    Mutsuo Yamaya

    2012-01-01

    Full Text Available Infection with respiratory viruses, including rhinoviruses, influenza virus, and respiratory syncytial virus, exacerbates asthma, which is associated with processes such as airway inflammation, airway hyperresponsiveness, and mucus hypersecretion. In patients with viral infections and with infection-induced asthma exacerbation, inflammatory mediators and substances, including interleukins (ILs, leukotrienes and histamine, have been identified in the airway secretions, serum, plasma, and urine. Viral infections induce an accumulation of inflammatory cells in the airway mucosa and submucosa, including neutrophils, lymphocytes and eosinophils. Viral infections also enhance the production of inflammatory mediators and substances in airway epithelial cells, mast cells, and other inflammatory cells, such as IL-1, IL-6, IL-8, GM-CSF, RANTES, histamine, and intercellular adhesion molecule-1. Viral infections affect the barrier function of the airway epithelial cells and vascular endothelial cells. Recent reports have demonstrated augmented viral production mediated by an impaired interferon response in the airway epithelial cells of asthma patients. Several drugs used for the treatment of bronchial asthma reduce viral and pro-inflammatory cytokine release from airway epithelial cells infected with viruses. Here, I review the literature on the pathogenesis of the viral infection-induced exacerbation of asthma and on the modulation of viral infection-induced airway inflammation.

  1. Evaluation of (99m)Tc(i)-tricarbonyl complexes of fluoroquinolones for targeting bacterial infection.

    Science.gov (United States)

    Nayak, Dipak Kumar; Baishya, Rinku; Halder, Kamal Krishna; Sen, Tuhinadri; Sarkar, Bharat R; Ganguly, Shantanu; Das, M K; Debnath, Mita Chatterjee

    2012-11-01

    The aim of this study was to develop (99m)Tc(CO)(3)-labeled fluoroquinolones as novel SPECT radiopharmaceuticals for imaging bacterial infection. Fluoroquinolones, e.g., ofloxacin (OFX), levofloxacin (LVX), lomefloxacin (LMX) and norfloxacin (NFX) were labeled with a fac-[(99m)Tc(CO)(3)(H(2)O)(3)](+) precursor. The radiochemical purity of the radiopharmaceuticals exceeded 97% as determined by thin layer chromatography and HPLC. No further purification was necessary before injection. The Re(CO)(3) complex of one of the fluoroquinolones (levofloxacin) was synthesized using [Re(CO)(3)(H(2)O)(3)]OTf and Re(CO)(5)Br precursors in separate experiments and characterized by IR, NMR and mass spectroscopic analysis. These studies revealed the formation of a single species in which the piperazinyl nitrogen and the -COOH group attached to the benzoxazine ring system of quinolone were involved in co-ordination to the Re(CO)(3) core. The HPLC elution pattern and retention time of the Re(CO)(3)-LVX complex were comparable to those of the corresponding (99m)Tc(CO)(3)-complex proving their similarity. When incubated in isotonic saline and serum up to 24 h (99m)Tc(CO)(3)-labeled fluoroquinolones exhibited good in vitro stability. Biodistribution studies performed at different time points on rats intramuscularly infected with S. aureus as well as on rats with sterile inflammation revealed a higher uptake in the infected area than the turpentine induced inflamed area. The uptake in infected thigh was significant with (99m)Tc(CO)(3)-OFX followed by (99m)Tc(CO)(3)-LVX. The mean ratios of the uptake in infected/non-infected thighs were 4.75 and 4.27 at 8 h and 24 h, respectively, for (99m)Tc(CO)(3)-OFX and 4.42 and 4.18 at 24 h and 8 h, respectively, for (99m)Tc(CO)(3)-LVX. The above abscess to muscle ratios were higher than reported for (99m)Tc-ciprofloxacin and other (99m)Tc-labeled fluoroquinolones. Scintigraphy studies also showed a significant uptake in the infectious lesions

  2. The clinical analysis of three methods in the treatment of intracranial bacterial infection

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Objective To analyze the effect of three therapeutic methods to find an optimal approach to the treatment of intracranial bacterial infection by retrospectively reviewing 33 intracranial bacterial infection patients who were admitted from 1995 to 2008 in our hospital.Methods The treatments by intermittent lumbar puncture,continuous lumbar subarachnoid space drainage,and embedment of Ommaya cyst for continuous drainage from the ventricles were performed in 15 cases,12 cases,and 6 cases respectively along wit...

  3. The Impact of Treated Bacterial Infections within One Month before Living Donor Liver Transplantation in Adults

    OpenAIRE

    Hara, Takanobu; Soyama, Akihiko; Takatsuki, Mitsuhisa; Hidaka, Masaaki; Carpenter, Izumi; Kinoshita, Ayaka; Adachi, Tomohiko; Kitasato, Amane; Kuroki, Tamotsu; Eguchi, Susumu

    2014-01-01

    Background: The impact of treated preoperative bacterial infections on the outcome of living-donor liver transplantation (LDLT) is not well defined. The aim of this study was to determine the frequency of pre-transplant bacterial infections within one month before LDLT and their impact on the post-transplant morbidity and mortality. Material/Methods: We retrospectively reviewed the records of 50 adult LDLT recipients between January 2009 and October 2011. Patients were divided into two gro...

  4. Stimulation of Host Immune Defenses by a Small Molecule Protects C. elegans from Bacterial Infection

    OpenAIRE

    Read Pukkila-Worley; Rhonda Feinbaum; Kirienko, Natalia V; Jonah Larkins-Ford; Conery, Annie L.; Ausubel, Frederick M.

    2012-01-01

    The nematode Caenorhabditis elegans offers currently untapped potential for carrying out high-throughput, live-animal screens of low molecular weight compound libraries to identify molecules that target a variety of cellular processes. We previously used a bacterial infection assay in C. elegans to identify 119 compounds that affect host-microbe interactions among 37,214 tested. Here we show that one of these small molecules, RPW-24, protects C. elegans from bacterial infection by stimulating...

  5. Listeria monocytogenes-induced bacterial peritonitis caused by contaminated cheese in a patient with haemochromatosis.

    Science.gov (United States)

    Galan, S R; Kann, P H; Gress, T M; Michl, P

    2011-07-01

    Infections with Listeria monocytogenes can present clinically with a wide range of different organ manifestations such as gastroenteritis, meningoencephalitis or osteomyelitis, posing a serious threat, particularly to immunocompromised patients. We present the case of a 76-year-old female patient with advanced liver disease due to underlying haemochromatosis, who was admitted to the hospital with increasing abdominal pain. She was diagnosed with spontaneous bacterial peritonitis caused by infection with Listeria monocytogenes, which she had acquired after consuming contaminated cheese from a local supermarket chain. To the best of our knowledge, this is the first case to describe Listeria-induced spontaneous bacterial peritonitis in a patient with haemochromatosis. Both end-stage liver disease and hereditary haemochromatosis on their own impair the local and systemic immune response, thereby representing predisposing factors for acquiring Listeria monocytogenes infection. This case demonstrates a rare organ manifestation of Listeria monocytogenes infection, which can be life-threatening if not diagnosed and treated adequately, and underlines the need to identify possible sources of infection in order to apply measures to prevent the further spread of the contaminated food.

  6. Autophagy Induced by Intracellular Infection of Propionibacterium acnes

    Science.gov (United States)

    Nakamura, Teruko; Furukawa, Asuka; Uchida, Keisuke; Ogawa, Tomohisa; Tamura, Tomoki; Sakonishi, Daisuke; Wada, Yuriko; Suzuki, Yoshimi; Ishige, Yuki; Minami, Junko; Akashi, Takumi

    2016-01-01

    Background Sarcoidosis is caused by Th1-type immune responses to unknown agents, and is linked to the infectious agent Propionibacterium acnes. Many strains of P. acnes isolated from sarcoid lesions cause intracellular infection and autophagy may contribute to the pathogenesis of sarcoidosis. We examined whether P. acnes induces autophagy. Methods Three cell lines from macrophages (Raw264.7), mesenchymal cells (MEF), and epithelial cells (HeLa) were infected by viable or heat-killed P. acnes (clinical isolate from sarcoid lymph node) at a multiplicity of infection (MOI) of 100 or 1000 for 1 h. Extracellular bacteria were killed by washing and culturing infected cells with antibiotics. Samples were examined by colony assay, electron-microscopy, and fluorescence-microscopy with anti-LC3 and anti-LAMP1 antibodies. Autophagy-deficient (Atg5-/-) MEF cells were also used. Results Small and large (≥5 μm in diameter) LC3-positive vacuoles containing few or many P. acnes cells (LC3-positive P. acnes) were frequently found in the three cell lines when infected by viable P. acnes at MOI 1000. LC3-positive large vacuoles were mostly LAMP1-positive. A few small LC3-positive/LAMP1-negative vacuoles were consistently observed in some infected cells for 24 h postinfection. The number of LC3-positive P. acnes was decreased at MOI 100 and completely abolished when heat-killed P. acnes was used. LC3-positive P. acnes was not found in autophagy-deficient Atg5-/- cells where the rate of infection was 25.3 and 17.6 times greater than that in wild-type Atg5+/+ cells at 48 h postinfection at MOI 100 and 1000, respectively. Electron-microscopic examination revealed bacterial cells surrounded mostly by a single-membrane including the large vacuoles and sometimes a double or multi-layered membrane, with occasional undigested bacterial cells in ruptured late endosomes or in the cytoplasm. Conclusion Autophagy was induced by intracellular P. acnes infection and contributed to intracellular

  7. IL-22 Controls Iron-Dependent Nutritional Immunity Against Systemic Bacterial Infections

    Science.gov (United States)

    Sakamoto, Kei; Kim, Yun-Gi; Hara, Hideki; Kamada, Nobuhiko; Caballero-Flores, Gustavo; Tolosano, Emanuela; Soares, Miguel P.; Puente, José L.; Inohara, Naohiro; Núñez, Gabriel

    2017-01-01

    Host immunity limits iron availability to pathogenic bacteria, but whether immunity limits pathogenic bacteria from accessing host heme, the major source of iron in the body, remains unclear. Using Citrobacter rodentium, a mouse enteric pathogen and Escherichia coli, a major cause of sepsis in humans as models, we find that interleukin-22, a cytokine best known for its ability to promote epithelial barrier function, also suppresses the systemic growth of bacteria by limiting iron availability to the pathogen. Using an unbiased proteomic approach to understand the mechanistic basis of IL-22 dependent iron retention in the host, we have identified that IL-22 induces the production of the plasma hemoglobin scavenger haptoglobin and heme scavenger hemopexin. Moreover, the anti-microbial effect of IL-22 depends on the induction of hemopexin expression, while haptogloblin is dispensable. Impaired pathogen clearance in infected Il22−/− mice was restored by hemopexin administration and hemopexin-deficient mice had increased pathogen loads after infection. These studies reveal a previously unrecognized host defense mechanism regulated by IL-22 that relies on the induction of hemopexin to limit heme availability to bacteria leading to suppression of bacterial growth during systemic infections. PMID:28286877

  8. Toxoplasma gondii profilin promotes recruitment of Ly6Chi CCR2+ inflammatory monocytes that can confer resistance to bacterial infection.

    Directory of Open Access Journals (Sweden)

    Lori M Neal

    2014-06-01

    Full Text Available Ly6C+ inflammatory monocytes are essential to host defense against Toxoplasma gondii, Listeria monocytogenes and other infections. During T. gondii infection impaired inflammatory monocyte emigration results in severe inflammation and failure to control parasite replication. However, the T. gondii factors that elicit these monocytes are unknown. Early studies from the Remington laboratory showed that mice with a chronic T. gondii infection survive lethal co-infections with unrelated pathogens, including L. monocytogenes, but a mechanistic analysis was not performed. Here we report that this enhanced survival against L. monocytogenes is due to early reduction of bacterial burdens and elicitation of Ly6C+ inflammatory monocytes. We demonstrate that a single TLR11/TLR12 ligand profilin (TgPRF was sufficient to reduce bacterial burdens similar to T. gondii chronic infection. Stimulation with TgPRF was also sufficient to enhance animal survival when administered either pre- or post-Listeria infection. The ability of TgPRF to reduce L. monocytogenes burdens was dependent on TLR11 and required IFN-γ but was not dependent on IL-12 signaling. TgPRF induced rapid production of MCP-1 and resulted in trafficking of Ly6Chi CCR2+ inflammatory monocytes and Ly6G+ neutrophils into the blood and spleen. Stimulation with TgPRF reduced L. monocytogenes burdens in mice depleted with the Ly6G specific MAb 1A8, but not in Ly6C/Ly6G specific RB6-8C5 depleted or CCR2-/- mice, indicating that only inflammatory monocytes are required for TgPRF-induced reduction in bacterial burdens. These results demonstrate that stimulation of TLR11 by TgPRF is a mechanism to promote the emigration of Ly6Chi CCR2+ monocytes, and that TgPRF recruited inflammatory monocytes can provide an immunological benefit against an unrelated pathogen.

  9. Bacterial adenosine triphosphate as a measure of urinary tract infection

    Science.gov (United States)

    Chappelle, E. W.; Picciolo, G. L.

    1971-01-01

    Procedure detects and counts bacteria present in urine samples. Method also determines bacterial levels in other aqueous body fluids including lymph fluid, plasma, blood, spinal fluid, saliva and mucous.

  10. High specificity ZnO quantum dots for diagnosis and treatment in bacterial infection

    Science.gov (United States)

    Zhang, Min; Qian, Zhiyu; Gu, Yueqing

    2016-03-01

    Early diagnosis and effective treatment of bacterial infection has become increasingly important. Herein, we developed a fluorescent nano-probe MPA@ZnO-PEP by conjugating SiO2-stabilized ZnO quantum dot (ZnO@SiO2) with bacteria-targeting peptide PEP, which was encapsulated with MPA, a near infrared (NIR) dye. The nanoprobe MPA@ZnO-PEP showed excellent fluorescence property and could specifically distinguish bacterial infection from sterile inflammation both in vitro and in vivo. The favorable biocompatability of MPA@ZnO-PEP was verified by MTT assay. This probe was further modified with antibiotic methicillin to form the theranostic nanoparticle MPA/Met@ZnO-PEP with amplified antibacterial activity. These results promised the great potential of MPA@ZnO-PEP for efficient non-invasive early diagnosis of bacterial infections and effective bacterial-targeting therapy.

  11. The Role of Bacterial Vaginosis in Infection After Major Gynecologic Surgery

    Directory of Open Access Journals (Sweden)

    L. Lin

    1999-01-01

    Full Text Available Purpose: Previous studies have reported an association between bacterial vaginosis (BV and postoperative fever and infection. This prospective study investigated whether the intermediate or definite stages of BV are risk factors for postoperative infection after major gynecologic surgery.

  12. Photodynamic antimicrobial chemotherapy using zinc phthalocyanine derivatives in treatment of bacterial skin infection

    Science.gov (United States)

    Chen, Zhuo; Zhang, Yaxin; Wang, Dong; Li, Linsen; Zhou, Shanyong; Huang, Joy H.; Chen, Jincan; Hu, Ping; Huang, Mingdong

    2016-01-01

    Photodynamic antimicrobial chemotherapy (PACT) is an effective method for killing bacterial cells in view of the increasing problem of multiantibiotic resistance. We herein reported the PACT effect on bacteria involved in skin infections using a zinc phthalocyanine derivative, pentalysine β-carbonylphthalocyanine zinc (ZnPc-Lys). Compared with its anionic ZnPc counterpart, ZnPc-Lys showed an enhanced antibacterial efficacy in vitro and in an animal model of localized infection. Meanwhile, ZnPc-Lys was observed to significantly reduce the wound skin blood flow during wound healing, indicating an anti-inflammation activity. This study provides new insight on the mechanisms of PACT in bacterial skin infection.

  13. Current concepts in the management of bacterial skin infections in children

    Directory of Open Access Journals (Sweden)

    Palit Aparna

    2010-01-01

    Full Text Available Bacterial skin infections in children vary widely clinically, starting from mild superficial folliculitis to deep necrotizing fasciitis. The causative organisms are mostly Staphylococcus aureus and Streptococcus, with occasional involvement of Gram-negative organisms. Treatment of even the milder forms of bacterial skin infections is of importance because of the long-term morbidity associated with them. However, because of global emergence of resistant strains of bacteria, treatment of these conditions is becoming increasingly difficult. The current antibacterial resistance patterns in organisms causing skin and soft tissue infections and the problems encountered in their management in children have been discussed.

  14. The clinical analysis of three methods in the treatment of intracranial bacterial infection

    Institute of Scientific and Technical Information of China (English)

    Rui-zhi Wang; Wei Shi

    2009-01-01

    Objective To analyze the effect of three therapeutic methods to find an optimal approach to the treatment of intracranial bacterial infection by retrospectively reviewing 33 intracranial bacterial infection patients who were admitted from 1995 to 2008 in oar hospital. Methods The treatments by intermittent lumbar puncture,continuous lumbar subarachnoid space drainage, and embedment of Ommaya cyst for continuous drainage from the ventricles were performed in 15 cases, 12 cases, and 6 cases respectively along with intravenous application of full dose of antibiotics. Results Nineteen cases were cured and the best prognosis was from the group of Ommaya cyst embedment and continuous drainage from the ventricles. Conclusion Management goals are prompt recognition of the central nervous system (CNS) infection, rapid identification of causative organisms and initiation of treatment with the optimal management methods for complications. Embedment of Ommaya cyst for continuous drainage from the ventricle is a safe and effective treatment for intracranial bacterial infection.

  15. Pathophysiology of bacterial infection of the central nervous system and its putative role in the pathogenesis of behavioral changes

    Directory of Open Access Journals (Sweden)

    Tatiana Barichello

    2013-03-01

    Full Text Available Invasion of the central nervous system (CNS by microorganisms is a severe and frequently fatal event during the course of many infectious diseases. It may lead to deafness, blindness, cerebral palsy, hydrocephalus, cognitive impairment or permanent neurological dysfunction in survivors. Pathogens can cross the blood-brain barrier by transcellular migration, paracellular migration and in infected macrophages. Pathogens may breach the blood-brain barrier and be recognized by antigen-presenting cells through the binding of Toll-like receptors. This induces the activation of nuclear factor kappa B or mitogen-activated protein kinase pathways and subsequently induces leukocyte infiltration and proliferation and the expression of numerous proteins involved in inflammation and the immune response. Many brain cells can produce cytokines, chemokines and other pro-inflammatory molecules in response to bacteria stimuli; as a consequence, polymorphonuclear cells are attracted and activated, and release large amounts of superoxide anion and nitric oxide, leading to peroxynitrite formation and oxidative stress. This cascade leads to lipid peroxidation, mitochondrial damage and blood-brain barrier breakdown, contributing to cellular injury during neuronal infection. Current evidence suggests that bacterial CNS infections can play a role in the etiopathogenesis of behavioral disorders by increasing pro-inflammatory cytokines and bacterial virulence factors. The aim of this review is to summarize the current knowledge of the relevant pathophysiologic steps in CNS infections.

  16. The Oral Bacterial Communities of Children with Well-Controlled HIV Infection and without HIV Infection.

    Directory of Open Access Journals (Sweden)

    Brittany E Goldberg

    Full Text Available The oral microbial community (microbiota plays a critical role in human health and disease. Alterations in the oral microbiota may be associated with disorders such as gingivitis, periodontitis, childhood caries, alveolar osteitis, oral candidiasis and endodontic infections. In the immunosuppressed population, the spectrum of potential oral disease is even broader, encompassing candidiasis, necrotizing gingivitis, parotid gland enlargement, Kaposi's sarcoma, oral warts and other diseases. Here, we used 454 pyrosequencing of bacterial 16S rRNA genes to examine the oral microbiome of saliva, mucosal and tooth samples from HIV-positive and negative children. Patient demographics and clinical characteristics were collected from a cross-section of patients undergoing routine dental care. Multiple specimens from different sampling sites in the mouth were collected for each patient. The goal of the study was to observe the potential diversity of the oral microbiota among individual patients, sample locations, HIV status and various dental characteristics. We found that there were significant differences in the microbiome among the enrolled patients, and between sampling locations. The analysis was complicated by uneven enrollment in the patient cohorts, with only five HIV-negative patients enrolled in the study and by the rapid improvement in the health of HIV-infected children between the time the study was conceived and completed. The generally good oral health of the HIV-negative patients limited the number of dental plaque samples that could be collected. We did not identify significant differences between well-controlled HIV-positive patients and HIV-negative controls, suggesting that well-controlled HIV-positive patients essentially harbor similar oral flora compared to patients without HIV. Nor were significant differences in the oral microbiota identified between different teeth or with different dental characteristics. Additional studies are

  17. [Microbiological diagnosis of bacterial infection associated with delivery and postpartum].

    Science.gov (United States)

    Padilla-Ortega, Belén; Delgado-Palacio, Susana; García-Garrote, Fernando; Rodríguez-Gómez, Juan Miguel; Romero-Hernández, Beatriz

    2016-05-01

    The newborn may acquire infections during delivery due to maternal colonization of the birth canal, by microorganisms such as Streptococcus agalactiae that caused early neonatal infection, or acquisition through the placenta, amniotic fluid or birth products. After birth, the newborn that needs hospitalization can develop nosocomial infections during their care and exceptionally through lactation by infectious mastitis or incorrect handling of human milk, which does not require to stop breastfeeding in most cases. It is important and necessary to perform microbiological diagnosis for the correct treatment of perinatal infections, especially relevant in preterm infants with low or very low weight with high mortality rates.

  18. Decreased effect of glucantime in cutaneous leishmaniasis complicated with secondary bacterial infection

    Directory of Open Access Journals (Sweden)

    G Sadeghian

    2011-01-01

    Full Text Available Background: Glucantime is regarded as the first-line treatment of cutaneous leishmaniasis (CL; however, failure to treatment is a problem in many cases. Aim: The aim was to evaluate the therapeutic effect of glucantime in CL complicated with secondary bacterial infection compared to uncomplicated lesions. Methods: This experimental study was performed in Skin Diseases and Leishmaniasis Research Center, Isfahan, Iran. A total of 161 patients enrolled in the study had CL confirmed by positive smear of lesions. All the patients were treated with systemic glucantime for 3 weeks and followed for 2 months. Response to treatment was defined as loss of infiltration, reepithelization, and negative smear. Depending on the results of bacterial cultures, the lesions were divided into two groups and the efficacy of glucantime was compared. Results: A total of 123 patients (76.4% were negative, and 38 patients (23.6% were positive for secondary bacterial infection. In groups with negative bacterial culture response to treatment was 65% (80 patients and in the other positive group, it was 31.6% (12 patients, with a difference (χ2 = 13.77, P < 0.01. Conclusion: Therapeutic effect of glucantime showed a decrease in CL lesions with secondary bacterial infection. Therefore, in the cases of unresponsiveness to treatment, the lesions should be evaluated for bacterial infection, before repeating the treatment.

  19. Label-free bimodal waveguide immunosensor for rapid diagnosis of bacterial infections in cirrhotic patients.

    Science.gov (United States)

    Maldonado, Jesús; González-Guerrero, Ana Belén; Domínguez, Carlos; Lechuga, Laura M

    2016-11-15

    Spontaneous bacterial peritonitis is an acute bacterial infection of ascitic fluid; it has a high incidence in cirrhotic patients and it is associated with high mortality. In such a situation, early diagnosis and treatment is crucial for the survival of the patient. However, bacterial analysis in ascitic fluid is currently based on culture methods, which are time-consuming and laborious. We report here the application of a photonic interferometer biosensor based on a bimodal waveguide (BiMW) for the rapid and label-free detection of bacteria directly in ascitic fluid. The device consists of a straight waveguide in which two modes of the same polarization interfere while interacting with the external medium through their evanescent fields. A bimolecular event occurring on the sensor area of the device (e.g. capturing bacteria) will differently affect each light mode, inducing a variation in the phase of the light exiting at the output of the waveguide. In this work, we demonstrate the quantitative detection of Bacillus cereus in buffer medium and Escherichia coli in undiluted ascitic fluid from cirrhotic patients. In the case of Bacillus cereus detection, the device was able to specifically detect bacteria at relevant concentrations in 12.5min and in the case of Escherichia coli detection, the analysis time was 25min. Extrapolation of the data demonstrated that the detection limits of the biosensor could reach few bacteria per milliliter. Based on the results obtained, we consider that the BiMW biosensor is positioned as a promising new clinical tool for user-friendly, cost-effective and real-time microbiological analysis.

  20. Hypoxia determines survival outcomes of bacterial infection through HIF-1alpha dependent re-programming of leukocyte metabolism *

    Science.gov (United States)

    Thompson, A.A.R.; Dickinson, R.S.; Murphy, F.; Thomson, J. P.; Marriott, H.M.; Tavares, A.; Willson, J.; Williams, L.; Lewis, A.; Mirchandani, A.; Dos Santos Coelho, P.; Doherty, C.; Ryan, E.; Watts, E.; Morton, N. M.; Forbes, S.; Stimson, R. H.; Hameed, A. G.; Arnold, N.; Preston, J.A.; Lawrie, A.; Finisguerra, V.; Mazzone, M.; Sadiku, P.; Goveia, J.; Taverna, F.; Carmeliet, P.; Foster, S.J.; Chilvers, E.R.; Cowburn, A.S.; Dockrell, D.H.; Johnson, R.S.; Meehan, R. R.; Whyte, M.K.B.; Walmsley, S.R.

    2017-01-01

    Hypoxia and bacterial infection frequently co-exist, in both acute and chronic clinical settings, and typically result in adverse clinical outcomes. To ameliorate this morbidity, we investigated the interaction between hypoxia and the host response. In the context of acute hypoxia, both S. aureus and S. pneumoniae infections rapidly induced progressive neutrophil mediated morbidity and mortality, with associated hypothermia and cardiovascular compromise. Preconditioning animals through longer exposures to hypoxia, prior to infection, prevented these pathophysiological responses and profoundly dampened the transcriptome of circulating leukocytes. Specifically, perturbation of HIF pathway and glycolysis genes by hypoxic preconditioning was associated with reduced leukocyte glucose utilisation, resulting in systemic rescue from a global negative energy state and myocardial protection. Thus we demonstrate that hypoxia preconditions the innate immune response and determines survival outcomes following bacterial infection through suppression of HIF-1α and neutrophil metabolism. The therapeutic implications of this work are that in the context of systemic or tissue hypoxia therapies that target the host response could improve infection associated morbidity and mortality. PMID:28386604

  1. [Resistance acquisition via the bacterial SOS response: the inducive role of antibiotics].

    Science.gov (United States)

    Da Re, Sandra; Ploy, Marie-Cécile

    2012-02-01

    After the euphoria of the antibiotic discovery and their tremendous action on bacterial infections outcomes, arrives a period of fear with the continuous emergence of bacteria that are resistant to almost all antibiotic treatments. It is becoming essential to better understand antibiotic resistance mechanisms to find new approaches to prevent the worldwide problem of multiresistance. The role of antibiotics on the direct induction of resistance acquisition is known. Recent studies have shown that some antibiotics, by inducing the bacterial SOS response, global repair response after DNA damages, are involved on a broader level in the induction, acquisition and dissemination of resistances in bacteria. We discuss here the role of antibiotics in resistance acquisition via the SOS response through several examples and the interest of identifying the SOS response regulators as the future targets of new families of antimicrobial molecules.

  2. The diagnostic value of CRP, IL-8, PCT, and sTREM-1 in the detection of bacterial infections in pediatric oncology patients with febrile neutropenia

    NARCIS (Netherlands)

    Miedema, Karin G. E.; de Bont, Eveline S. J. M.; Elferink, Rob F. M. Oude; van Vliet, Michel J.; Nijhuis, Claudi S. M. Oude; Kamps, Willem A.; Tissing, Wim J. E.

    2011-01-01

    In this study, we evaluated C-reactive protein (CRP), interleukin (IL)-8, procalcitonin (PCT), and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) as predictors for bacterial infection in febrile neutropenia, plus their usefulness in febrile neutropenia during chemotherapy-induced

  3. Thrombin-activatable fibrinolysis inhibitor and bacterial infections

    NARCIS (Netherlands)

    Valls Serón, M.

    2011-01-01

    Mercedes Valls Serón onderzocht een onderdeel van het fibrinolytische systeem dat verantwoordelijk is voor het oplossen van bloedstolsels. Ze keek naar de wisselwerking tussen de zogenaamde trombine-activeerbare fibrinolyse inhibitors - of TAFI - en bacteriën. De binding van TAFI aan een specifieke

  4. Insights into the bacterial and fungal ecology of endodontic infections

    NARCIS (Netherlands)

    Persoon, I.F.

    2016-01-01

    In apical periodontitis, microorganisms infect the dental root canal system and evoke an inflammation in the periapical tissues. Since the host is unable to eliminate this infection, the root canal system has to be disinfected by the dentist during endodontic therapy. After this the inflammation sho

  5. Comparative study of bacterial infection prevalence between cirrhotic patients with and without upper gastrointestinal bleeding

    Directory of Open Access Journals (Sweden)

    Delvone Almeida

    2001-06-01

    Full Text Available Bacterial infection is a frequent complication in patients with chronic liver disease, mainly during the advanced stages. There is evidence that the main factors that contribute to a predisposition to infection in cirrhotic patients are related to hepatic failure with consequent immunodeficiency. Invasive procedures (diagnostic or therapeutic can predispose to bacterial infections, and upper gastrointestinal bleeding (UGB is considered a potentially important risk factor. A group of cirrhotic patients (child B and C Pugh groups were evaluated retrospectively by chart reviews regarding the prevalence of bacterial infection during hospitalization to determine whether UGB was a risk factor. An infection was considered present if a specific organ system was identified or if fever (>38ºC persisted for more than 24 hours with associated leukocytosis. Spontaneous bacterial peritonitis was based on classical criteria. Eighty-nine patients were evaluated. Fourty-six patients presented with UGB, and 43 patients had no UGB (control. There were infections recorded in 25/46 (54% patients with UGB, and 15/43 (35% in those without UGB (p=0.065. The ratio of the number of infections/admitted patients, was significantly larger in the group with UGB (0.78 ± 0.89 vs. 0.39 ± 0.62; p=0.028 since patients had more than one infection. In the UGB group compared to non UGB group, ascites was more frequent (67% vs. 42%; p=0.027; they were more likely to have undergone endoscopic procedures (p<0.001 and the mean ± SD for platelets count was smaller (96,114 ± 57,563 vs. 145,674 ± 104,083; p=0.007. The results show that UGB is an important contribution to bacterial infection among Child B and C cirrhotic patients.

  6. The Diagnostic and Prognostic Accuracy of Five Markers of Serious Bacterial Infection in Malawian Children with Signs of Severe Infection

    OpenAIRE

    Carrol, Enitan D.; Mankhambo, Limangeni A.; Graham Jeffers; Deborah Parker; Malcolm Guiver; Paul Newland; Banda, Daniel L; Molyneux, Elizabeth M.; Heyderman, Robert S; Molyneux, Malcolm E.; C Anthony Hart

    2009-01-01

    BACKGROUND: Early recognition and prompt and appropriate antibiotic treatment can significantly reduce mortality from serious bacterial infections (SBI). The aim of this study was to evaluate the utility of five markers of infection: C-reactive protein (CRP), procalcitonin (PCT), soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), CD163 and high mobility group box-1 (HMGB1), as markers of SBI in severely ill Malawian children. METHODOLOGY AND PRINCIPAL FINDINGS: Children prese...

  7. The role of T cell subsets and cytokines in the regulation of intracellular bacterial infection

    Directory of Open Access Journals (Sweden)

    Oliveira S.C.

    1998-01-01

    Full Text Available Cellular immune responses are a critical part of the host's defense against intracellular bacterial infections. Immunity to Brucella abortus crucially depends on antigen-specific T cell-mediated activation of macrophages, which are the major effectors of cell-mediated killing of this organism. T lymphocytes that proliferate in response to B. abortus were characterized for phenotype and cytokine activity. Human, murine, and bovine T lymphocytes exhibited a type 1 cytokine profile, suggesting an analogous immune response in these different hosts. In vivo protection afforded by a particular cell type is dependent on the antigen presented and the mechanism of antigen presentation. Studies using MHC class I and class II knockout mice infected with B. abortus have demonstrated that protective immunity to brucellosis is especially dependent on CD8+ T cells. To target MHC class I presentation we transfected ex vivo a murine macrophage cell line with B. abortus genes and adoptively transferred them to BALB/c mice. These transgenic macrophage clones induced partial protection in mice against experimental brucellosis. Knowing the cells required for protection, vaccines can be designed to activate the protective T cell subset. Lastly, as a new strategy for priming a specific class I-restricted T cell response in vivo, we used genetic immunization by particle bombardment-mediated gene transfer

  8. Host-induced bacterial cell wall decomposition mediates pattern-triggered immunity in Arabidopsis.

    Science.gov (United States)

    Liu, Xiaokun; Grabherr, Heini M; Willmann, Roland; Kolb, Dagmar; Brunner, Frédéric; Bertsche, Ute; Kühner, Daniel; Franz-Wachtel, Mirita; Amin, Bushra; Felix, Georg; Ongena, Marc; Nürnberger, Thorsten; Gust, Andrea A

    2014-06-23

    Peptidoglycans (PGNs) are immunogenic bacterial surface patterns that trigger immune activation in metazoans and plants. It is generally unknown how complex bacterial structures such as PGNs are perceived by plant pattern recognition receptors (PRRs) and whether host hydrolytic activities facilitate decomposition of bacterial matrices and generation of soluble PRR ligands. Here we show that Arabidopsis thaliana, upon bacterial infection or exposure to microbial patterns, produces a metazoan lysozyme-like hydrolase (lysozyme 1, LYS1). LYS1 activity releases soluble PGN fragments from insoluble bacterial cell walls and cleavage products are able to trigger responses typically associated with plant immunity. Importantly, LYS1 mutant genotypes exhibit super-susceptibility to bacterial infections similar to that observed on PGN receptor mutants. We propose that plants employ hydrolytic activities for the decomposition of complex bacterial structures, and that soluble pattern generation might aid PRR-mediated immune activation in cell layers adjacent to infection sites.

  9. Adaptive Remodeling of the Bacterial Proteome by Specific Ribosomal Modification Regulates Pseudomonas Infection and Niche Colonisation.

    Science.gov (United States)

    Little, Richard H; Grenga, Lucia; Saalbach, Gerhard; Howat, Alexandra M; Pfeilmeier, Sebastian; Trampari, Eleftheria; Malone, Jacob G

    2016-02-01

    Post-transcriptional control of protein abundance is a highly important, underexplored regulatory process by which organisms respond to their environments. Here we describe an important and previously unidentified regulatory pathway involving the ribosomal modification protein RimK, its regulator proteins RimA and RimB, and the widespread bacterial second messenger cyclic-di-GMP (cdG). Disruption of rimK affects motility and surface attachment in pathogenic and commensal Pseudomonas species, with rimK deletion significantly compromising rhizosphere colonisation by the commensal soil bacterium P. fluorescens, and plant infection by the pathogens P. syringae and P. aeruginosa. RimK functions as an ATP-dependent glutamyl ligase, adding glutamate residues to the C-terminus of ribosomal protein RpsF and inducing specific effects on both ribosome protein complement and function. Deletion of rimK in P. fluorescens leads to markedly reduced levels of multiple ribosomal proteins, and also of the key translational regulator Hfq. In turn, reduced Hfq levels induce specific downstream proteomic changes, with significant increases in multiple ABC transporters, stress response proteins and non-ribosomal peptide synthetases seen for both ΔrimK and Δhfq mutants. The activity of RimK is itself controlled by interactions with RimA, RimB and cdG. We propose that control of RimK activity represents a novel regulatory mechanism that dynamically influences interactions between bacteria and their hosts; translating environmental pressures into dynamic ribosomal changes, and consequently to an adaptive remodeling of the bacterial proteome.

  10. Adaptive Remodeling of the Bacterial Proteome by Specific Ribosomal Modification Regulates Pseudomonas Infection and Niche Colonisation.

    Directory of Open Access Journals (Sweden)

    Richard H Little

    2016-02-01

    Full Text Available Post-transcriptional control of protein abundance is a highly important, underexplored regulatory process by which organisms respond to their environments. Here we describe an important and previously unidentified regulatory pathway involving the ribosomal modification protein RimK, its regulator proteins RimA and RimB, and the widespread bacterial second messenger cyclic-di-GMP (cdG. Disruption of rimK affects motility and surface attachment in pathogenic and commensal Pseudomonas species, with rimK deletion significantly compromising rhizosphere colonisation by the commensal soil bacterium P. fluorescens, and plant infection by the pathogens P. syringae and P. aeruginosa. RimK functions as an ATP-dependent glutamyl ligase, adding glutamate residues to the C-terminus of ribosomal protein RpsF and inducing specific effects on both ribosome protein complement and function. Deletion of rimK in P. fluorescens leads to markedly reduced levels of multiple ribosomal proteins, and also of the key translational regulator Hfq. In turn, reduced Hfq levels induce specific downstream proteomic changes, with significant increases in multiple ABC transporters, stress response proteins and non-ribosomal peptide synthetases seen for both ΔrimK and Δhfq mutants. The activity of RimK is itself controlled by interactions with RimA, RimB and cdG. We propose that control of RimK activity represents a novel regulatory mechanism that dynamically influences interactions between bacteria and their hosts; translating environmental pressures into dynamic ribosomal changes, and consequently to an adaptive remodeling of the bacterial proteome.

  11. Dietary Fatty Acids and Immune Response to Food-Borne Bacterial Infections

    OpenAIRE

    2013-01-01

    Functional innate and acquired immune responses are required to protect the host from pathogenic bacterial infections. Modulation of host immune functions may have beneficial or deleterious effects on disease outcome. Different types of dietary fatty acids have been shown to have variable effects on bacterial clearance and disease outcome through suppression or activation of immune responses. Therefore, we have chosen to review research across experimental models and food sources on the effec...

  12. Differential effects of gram-positive and gram-negative bacterial products on morphine induced inhibition of phagocytosis.

    Science.gov (United States)

    Ninkovic, Jana; Jana, Ninkovic; Anand, Vidhu; Vidhu, Anand; Dutta, Raini; Raini, Dutta; Zhang, Li; Saluja, Anuj; Meng, Jingjing; Koodie, Lisa; Lisa, Koodie; Banerjee, Santanu; Santanu, Banerjee; Roy, Sabita; Sabita, Roy

    2016-02-19

    Opioid drug abusers have a greater susceptibility to gram positive (Gram (+)) bacterial infections. However, the mechanism underlying opioid modulation of Gram (+) versus Gram (-) bacterial clearance has not been investigated. In this study, we show that opioid treatment resulted in reduced phagocytosis of Gram (+), when compared to Gram (-) bacteria. We further established that LPS priming of chronic morphine treated macrophages leads to potentiated phagocytosis and killing of both Gram (+) and Gram (-) bacteria in a P-38 MAP kinase dependent signaling pathway. In contrast, LTA priming lead to inhibition of both phagocytosis and bacterial killing. This study demonstrates for the first time the differential effects of TLR4 and TLR2 agonists on morphine induced inhibition of phagocytosis. Our results suggest that the incidence and severity of secondary infections with Gram (+) bacteria would be higher in opioid abusers.

  13. Spontaneous Bacterial Peritonitis Caused by Infection with Listeria monocytogenes

    Directory of Open Access Journals (Sweden)

    Michael Vincent F. Tablang

    2008-11-01

    Full Text Available Spontaneous bacterial peritonitis is a severe and life-threatening complication in patients with ascites caused by advanced liver disease. The organisms most commonly involved are coliform bacteria and third-generation cephalosporins are the empiric antibiotics of choice. This is an uncommon case of spontaneous bacterial peritonitis caused by Listeria monocytogenes in a female patient with liver cirrhosis from autoimmune hepatitis. She did not improve with ceftriaxone and her course was complicated by hepatic encephalopathy, seizures and multi-organ failure. This case emphasizes that a high index of suspicion should be maintained for timely diagnosis and treatment. Listerial peritonitis should be suspected in patients with end-stage liver disease and inadequate response to conventional antibiotics within 48–72 h. Ampicillin/sulbactam should be initiated while awaiting results of ascitic fluid or blood culture.

  14. Parasites can enhance infections of fish with bacterial pathogens

    Science.gov (United States)

    In aquaculture systems, fish are commonly infected by multiple pathogens, including parasites. Parasite Ichthyophthirius multifiliis (Ich) and bacterium Edwardsiella ictaluri are two common pathogens of cultured channel catfish. The objectives were to 1) evaluate the susceptibility of Ich parasitize...

  15. Findings of bacterial microflora in piglets infected with conventional swine plague

    Directory of Open Access Journals (Sweden)

    Prodanov Jasna

    2002-01-01

    Full Text Available Piglets infected with the conventional swine plague virus as a result of secondary bacterial infections sometimes show an insufficiently clear clinical and pathoanatomical picture, which is why the very procedure of diagnosis is complex and the final diagnosis unreliable. That is why these investigations were aimed at examining the presence of bacterial microflora in diseased and dead pilgets which were found to have the viral antigen for CSP using the fluorescent antibody technique, in cases where the pathomorphological finding was not characteristic for conventional swine plague. Autopsies of dead piglets most often showed changes in the digestive tract and lungs, with resulting technopathy and diseases of infective nature. Such findings on knowledge of a present bacterial microflora are especially important in cases when conventional swine plague is controlled on farms and an announcement that the disease has been contained is in the offing.

  16. Low dietary iron intake restrains the intestinal inflammatory response and pathology of enteric infection by food-borne bacterial pathogens.

    Science.gov (United States)

    Kortman, Guus A M; Mulder, Michelle L M; Richters, Thijs J W; Shanmugam, Nanda K N; Trebicka, Estela; Boekhorst, Jos; Timmerman, Harro M; Roelofs, Rian; Wiegerinck, Erwin T; Laarakkers, Coby M; Swinkels, Dorine W; Bolhuis, Albert; Cherayil, Bobby J; Tjalsma, Harold

    2015-09-01

    Orally administrated iron is suspected to increase susceptibility to enteric infections among children in infection endemic regions. Here we investigated the effect of dietary iron on the pathology and local immune responses in intestinal infection models. Mice were held on iron-deficient, normal iron, or high iron diets and after 2 weeks they were orally challenged with the pathogen Citrobacter rodentium. Microbiome analysis by pyrosequencing revealed profound iron- and infection-induced shifts in microbiota composition. Fecal levels of the innate defensive molecules and markers of inflammation lipocalin-2 and calprotectin were not influenced by dietary iron intervention alone, but were markedly lower in mice on the iron-deficient diet after infection. Next, mice on the iron-deficient diet tended to gain more weight and to have a lower grade of colon pathology. Furthermore, survival of the nematode Caenorhabditis elegans infected with Salmonella enterica serovar Typhimurium was prolonged after iron deprivation. Together, these data show that iron limitation restricts disease pathology upon bacterial infection. However, our data also showed decreased intestinal inflammatory responses of mice fed on high iron diets. Thus additionally, our study indicates that the effects of iron on processes at the intestinal host-pathogen interface may highly depend on host iron status, immune status, and gut microbiota composition.

  17. Secreted Bacterial Effectors and Host-Produced Eiger/TNF Drive Death in aSalmonella-Infected Fruit Fly.

    Directory of Open Access Journals (Sweden)

    Stephanie M Brandt

    2004-12-01

    Full Text Available Death by infection is often as much due to the host's reaction as it is to the direct result of microbial action. Here we identify genes in both the host and microbe that are involved in the pathogenesis of infection and disease in Drosophila melanogaster challenged with Salmonella enterica serovartyphimurium (S. typhimurium. We demonstrate that wild-typeS. typhimurium causes a lethal systemic infection when injected into the hemocoel of D. melanogaster. Deletion of the gene encoding the secreted bacterial effect or Salmonella leucine-rich (PslrPchanges an acute and lethal infection to one that is persistent and less deadly. We propose a model in which Salmonella secreted effectors stimulate the fly and thus cause an immune response that is damaging both to the bacteria and, subsequently, to the host. In support of this model, we show that mutations in the fly gene eiger, a TNF homolog, delay the lethality of Salmonella infection. These results suggest that S. typhimurium-infected flies die from a condition that resembles TNF-induced metabolic collapse in vertebrates. This idea provides us with a new model to study shock-like biology in a genetically manipulable host. In addition, it allows us to study the difference in pathways followed by a microbe when producing an acute or persistent infection.

  18. Bacterial canker on kiwifruit in Italy: anatomical changes in the wood and in the primary infection sites.

    Science.gov (United States)

    Renzi, Marsilio; Copini, Paul; Taddei, Anna R; Rossetti, Antonio; Gallipoli, Lorenzo; Mazzaglia, Angelo; Balestra, Giorgio M

    2012-09-01

    The bacterial canker of kiwifruit caused by Pseudomonas syringae pv. actinidiae is a severe threat to kiwifruit production worldwide. Many aspects of P. syringae pv. actinidiae biology and epidemiology still require in-depth investigation. The infection by and spread of P. syringae pv. actinidiae in xylem and phloem was investigated by carrying out artificial inoculation experiments with histological and dendrochronological analyses of naturally diseased plants in Italy. We found that the bacterium can infect host plants by entering natural openings and lesions. In naturally infected kiwifruit plants, P. syringae pv. actinidiae is present in the lenticels as well as in the dead phloem tissue beneath the lenticels, surrounded by a lesion in the periderm which appears to indicate the importance of lenticels to kiwifruit infection. Biofilm formation was observed outside and inside plants. In cases of advanced stages of P. syringae pv. actinidiae infection, neuroses of the phloem occur, which are followed by cambial dieback and most likely by infection of the xylem. Anatomical changes in wood such as reduced ring width, a drastic reduction in vessel size, and the presence of tyloses were observed within several infected sites. In the field, these changes occur only a year after the first leaf symptoms are observed suggesting a significant time lapse between primary and secondary symptoms. It was possible to study the temporal development of P. syringae pv. actinidiae-induced cambial dieback by applying dendrochronology methods which revealed that cambial dieback occurs only during the growing season.

  19. Bacterial-excreted small volatile molecule 2-aminoacetophenone induces oxidative stress and apoptosis in murine skeletal muscle.

    Science.gov (United States)

    Bandyopadhaya, Arunava; Constantinou, Caterina; Psychogios, Nikolaos; Ueki, Ryusuke; Yasuhara, Shingo; Martyn, J A Jeevendra; Wilhelmy, Julie; Mindrinos, Michael; Rahme, Laurence G; Tzika, A Aria

    2016-04-01

    Oxidative stress induces mitochondrial dysfunction and facilitates apoptosis, tissue damage or metabolic alterations following infection. We have previously discovered that the Pseudomonas aeruginosa (PA) quorum sensing (QS)-excreted small volatile molecule, 2-aminoacetophenone (2-AA), which is produced in infected human tissue, promotes bacterial phenotypes that favor chronic infection, while also dampening the pathogen‑induced innate immune response, thus compromising muscle function and promoting host tolerance to infection. In this study, murine whole-genome expression data have demonstrated that 2-AA affects the expression of genes involved in reactive oxygen species (ROS) homeostasis, thus producing an oxidative stress signature in skeletal muscle. The results of the present study demonstrated that the expression levels of genes involved in apoptosis signaling pathways were upregulated in the skeletal muscle of 2-AA-treated mice. To confirm the results of our transcriptome analysis, we used a novel high-resolution magic-angle-spinning (HRMAS), proton (1H) nuclear magnetic resonance (NMR) method and observed increased levels of bisallylic methylene fatty acyl protons and vinyl protons, suggesting that 2-AA induces skeletal muscle cell apoptosis. This effect was corroborated by our results demonstrating the downregulation of mitochondrial membrane potential in vivo in response to 2-AA. The findings of the present study indicate that the bacterial infochemical, 2-AA, disrupts mitochondrial functions by inducing oxidative stress and apoptosis signaling and likely promotes skeletal muscle dysfunction, which may favor chronic/persistent infection.

  20. Streptococcus oralis Induces Lysosomal Impairment of Macrophages via Bacterial Hydrogen Peroxide.

    Science.gov (United States)

    Okahashi, Nobuo; Nakata, Masanobu; Kuwata, Hirotaka; Kawabata, Shigetada

    2016-07-01

    Streptococcus oralis, an oral commensal, belongs to the mitis group of streptococci and occasionally causes opportunistic infections, such as bacterial endocarditis and bacteremia. Recently, we found that the hydrogen peroxide (H2O2) produced by S. oralis is sufficient to kill human monocytes and epithelial cells, implying that streptococcal H2O2 is a cytotoxin. In the present study, we investigated whether streptococcal H2O2 impacts lysosomes, organelles of the intracellular digestive system, in relation to cell death. S. oralis infection induced the death of RAW 264 macrophages in an H2O2-dependent manner, which was exemplified by the fact that exogenous H2O2 also induced cell death. Infection with either a mutant lacking spxB, which encodes pyruvate oxidase responsible for H2O2 production, or Streptococcus mutans, which does not produce H2O2, showed less cytotoxicity. Visualization of lysosomes with LysoTracker revealed lysosome deacidification after infection with S. oralis or exposure to H2O2, which was corroborated by acridine orange staining. Similarly, fluorescent labeling of lysosome-associated membrane protein-1 gradually disappeared during infection with S. oralis or exposure to H2O2 The deacidification and the following induction of cell death were inhibited by chelating iron in lysosomes. Moreover, fluorescent staining of cathepsin B indicated lysosomal destruction. However, treatment of infected cells with a specific inhibitor of cathepsin B had negligible effects on cell death; instead, it suppressed the detachment of dead cells from the culture plates. These results suggest that streptococcal H2O2 induces cell death with lysosomal destruction and then the released lysosomal cathepsins contribute to the detachment of the dead cells.

  1. Effect of dietary antioxidant supplementation (Cuminum cyminum) on bacterial susceptibility of diabetes-induced rats.

    Science.gov (United States)

    Moubarz, Gehan; Embaby, Mohamed A; Doleib, Nada M; Taha, Mona M

    2016-01-01

    Diabetic patients are at risk of acquiring infections. Chronic low-grade inflammation is an important factor in the pathogenesis of diabetic complication. Diabetes causes generation of reactive oxygen species that increases oxidative stress, which may play a role in the development of complications as immune-deficiency and bacterial infection. The study aimed to investigate the role of a natural antioxidant, cumin, in the improvement of immune functions in diabetes. Diabetes was achieved by interperitoneal injection of streptozotocin (STZ). Bacterial infection was induced by application of Staphylococcus aureus suspension to a wound in the back of rats. The antioxidant was administered for 6 weeks. Results revealed a decrease in blood glucose levels in diabetic rats (p < 0.001), in addition to improving immune functions by decreasing total IgE approaching to the normal control level. Also, inflammatory cytokine (IL-6, IL-1β and TNF) levels, as well as total blood count decreased in diabetic rats as compared to the control group. Thus, cumin may serve as anti-diabetic treatment and may help in attenuating diabetic complications by improving immune functions. Therefore, a medical dietary antioxidant supplementation is important to improve the immune functions in diabetes.

  2. Early diagnosis of bacterial and fungal infection in chronic cholestatic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Xiong-Zhi Wu; Dan Chen; Lian-San Zhao; Xiao-Hui Yu; Mei Wei; Yan Zhao; Qing Fang; Qian Xu

    2004-01-01

    AIM: To investigate the early diagnostic methods of bacterial and fungal infection in patients with chronic cholestatic hepatitis B.METHODS: One hundred and one adult in-patients with chronic hepatitis B were studied and divided into 3 groups:direct bilirubin (DBil)/total bilirubin (TBil)≥0.5, without bacterial and fungal infection (group A, n=38); DBil/TBil <0.5, without bacterial and fungal infection (group B, n=23);DBil/TBil≥0.5, with bacterial or fungal infection (group C,n=40). The serum biochemical index and pulse rate were analyzed.RESULTS: Level of TBil, DBil, alkaline phosphatase (ALP)and DBil/ALP in group A increased compared with that in group B. The level of ALP in group C decreased compared with that in group A, whereas the level of TBil, DBil and DBil/ALP increased (ALP: 156±43, 199±68, respectively,P<0.05; TBil: 370±227, 220±206, respectively, P<0.01;DBil: 214±143, 146±136, respectively, P<0.01; DBil/ALP:1.65±1.05, 0.78±0.70, respectively, P<0.001). The level of DBil and infection affected DBil/ALP. Independent of the effect of DBil, infection caused DBil/ALP to rise (P<0.05).The pulse rate in group A decreased compared with that in group B (63.7±6.4, 77.7±11.4, respectively, P<0.001),and the pulse rate in group C increased compared with that in group A (81.2±12.2, 63.7±6.4, respectively, P<0.001).The equation (infection=0.218 pusle rate +1.064 DBil/ALP -16.361), with total accuracy of 85.5%, was obtained from stepwise logistic regression. Pulse rate (≥80/min) and DBil/ALP (≥1.0) were used to screen infection. The sensitivity was 62.5% and 64.7% respectively, and the specificity was 100% and 82.8% respectively.CONCLUSION: Bacterial and fungal infection deteriorate jaundice and increase pulse rate, decrease serum ALP and increase DBil/ALP. Pulse rate, DBil/ALP and the equation (infection=0.218 pusle rate+1.064 DBil/ALP-16.361) are helpful to early diagnosis of bacterial and fungal infection in patients with chronic

  3. Perinatal Exposure to Environmental Tobacco Smoke (ETS Enhances Susceptibility to Viral and Secondary Bacterial Infections

    Directory of Open Access Journals (Sweden)

    Jocelyn A. Claude

    2012-10-01

    Full Text Available Studies suggest childhood exposure to environmental tobacco smoke (ETS leads to increased incidence of infections of the lower respiratory tract. The objective of this study was to determine whether perinatal exposure to ETS increases the incidence, morbidity and severity of respiratory influenza infection and whether a secondary bacterial challenge at the peak of a pre-existing viral infection creates an enhanced host-pathogen susceptibility to an opportunistic infection. Timed-pregnant female Balb/c mice were exposed to either ETS for 6 h/day, 7 d/week beginning on gestation day 14 and continuing with the neonates to 6 weeks of age. Control animals were exposed to filtered air (FA. At the end of exposure, mice were intranasally inoculated with a murine-adapted influenza A. One week later, an intranasal inoculation of S. aureus bacteria was administered. The respective treatment groups were: bacteria only, virus only or virus+bacteria for both FA and ETS-exposed animals for a total of six treatment groups. Animal behavior and body weights were documented daily following infection. Mice were necropsied 1-day post-bacterial infection. Bronchoalveolar lavage fluid (BALF cell analysis demonstrated perinatal exposure to ETS, compared to FA, leads to delayed but enhanced clinical symptoms and enhanced total cell influx into the lungs associated with viral infection followed by bacterial challenge. Viral infection significantly increases the number of neutrophils entering the lungs following bacterial challenge with either FA or ETS exposure, while the influx of lymphocytes and monocytes is significantly enhanced only by perinatal ETS exposure. There is a significant increase in peribronchiolar inflammation following viral infection in pups exposed to ETS compared with pups exposed to FA, but no change is noted in the degree of lung injury between FA and ETS-exposed animals following bacterial challenge. The data suggests perinatal exposure to ETS

  4. Glutamine deamidation and dysfunction of ubiquitin/NEDD8 induced by a bacterial effector family.

    Science.gov (United States)

    Cui, Jixin; Yao, Qing; Li, Shan; Ding, Xiaojun; Lu, Qiuhe; Mao, Haibin; Liu, Liping; Zheng, Ning; Chen, She; Shao, Feng

    2010-09-03

    A family of bacterial effectors including Cif homolog from Burkholderia pseudomallei (CHBP) and Cif from Enteropathogenic Escherichia coli (EPEC) adopt a functionally important papain-like hydrolytic fold. We show here that CHBP was a potent inhibitor of the eukaryotic ubiquitination pathway. CHBP acted as a deamidase that specifically and efficiently deamidated Gln40 in ubiquitin and ubiquitin-like protein NEDD8 both in vitro and during Burkholderia infection. Deamidated ubiquitin was impaired in supporting ubiquitin-chain synthesis. Cif selectively deamidated NEDD8, which abolished the activity of neddylated Cullin-RING ubiquitin ligases (CRLs). Ubiquitination and ubiquitin-dependent degradation of multiple CRL substrates were impaired by Cif in EPEC-infected cells. Mutations of substrate-contacting residues in Cif abolished or attenuated EPEC-induced cytopathic phenotypes of cell cycle arrest and actin stress fiber formation.

  5. Bacterial persistence induced by salicylate via reactive oxygen species

    Science.gov (United States)

    Wang, Tiebin; El Meouche, Imane; Dunlop, Mary J.

    2017-01-01

    Persisters are phenotypic variants of regular cells that exist in a dormant state with low metabolic activity, allowing them to exhibit high tolerance to antibiotics. Despite increasing recognition of their role in chronic and recalcitrant infections, the mechanisms that induce persister formation are not fully understood. In this study, we find that salicylate can induce persister formation in Escherichia coli via generation of reactive oxygen species (ROS). Salicylate-induced ROS cause a decrease in the membrane potential, reduce metabolism and lead to an increase in persistence. These effects can be recovered by culturing cells in the presence of a ROS quencher or in an anaerobic environment. Our findings reveal that salicylate-induced oxidative stress can lead to persistence, suggesting that ROS, and their subsequent impact on membrane potential and metabolism, may play a broad role in persister formation. PMID:28281556

  6. Organelle targeting during bacterial infection: insights from Listeria.

    Science.gov (United States)

    Lebreton, Alice; Stavru, Fabrizia; Cossart, Pascale

    2015-06-01

    Listeria monocytogenes, a facultative intracellular bacterium responsible for severe foodborne infections, is now recognized as a multifaceted model in infection biology. Comprehensive studies of the molecular and cellular basis of the infection have unraveled how the bacterium crosses the intestinal and feto-placental barriers, invades several cell types in which it multiplies and moves, and spreads from cell to cell. Interestingly, although Listeria does not actively invade host cell organelles, it can interfere with their function. We discuss the effect of Listeria on the endoplasmic reticulum (ER) and the mechanisms leading to the fragmentation of the mitochondrial network and its consequences, and review the strategies used by Listeria to subvert nuclear functions, more precisely to control host gene expression at the chromatin level.

  7. Bacterial DNA induces the complement system activation in serum and ascitic fluid from patients with advanced cirrhosis.

    Science.gov (United States)

    Francés, Rubén; González-Navajas, José M; Zapater, Pedro; Muñoz, Carlos; Caño, Rocío; Pascual, Sonia; Márquez, Dorkas; Santana, Francia; Pérez-Mateo, Miguel; Such, José

    2007-07-01

    Translocation of intestinal bacteria to ascitic fluid is, probably, the first step in the development of spontaneous bacterial peritonitis in patients with cirrhosis. Proteins of the complement system are soluble mediators implicated in the host immune response to bacterial infections and its activation has been traditionally considered to be an endotoxin-induced phenomenon. The aim of this study was to compare the modulation of these proteins in response to the presence of bacterial DNA and/or endotoxin in patients with advanced cirrhosis and ascites in different clinical conditions. Groups I and II consisted of patients without/with bacterial DNA. Group III included patients with spontaneous bacterial peritonitis and Group IV with patients receiving norfloxacin as secondary long-term prophylaxis of spontaneous bacterial peritonitis. Serum and ascitic fluid levels of endotoxin and truncated residues of the complement system were measured by ELISA. The complement system is triggered in response to bacterial DNA, as evidenced by significantly increased levels of C3b, membrane attack complex, and C5a in patients from Groups II and III compared with patients without bacterial DNA (Group I) and those receiving norfloxacin (Group IV). Gram classification did not further differentiate the immune response between patients within groups II and III, even though endotoxin levels were, as expected, significantly higher in patients with bacterial DNA from gram-negative microorganisms. The complement protein activation observed in patients with bacterial DNA in blood and ascitic fluid is indistinguishable from that observed in patients with spontaneous bacterial peritonitis and may occur in an endotoxin-independent manner.

  8. Pathogen-induced conditioning of the primary xylem vessels - a prerequisite for the formation of bacterial emboli by Pectobacterium atrosepticum.

    Science.gov (United States)

    Gorshkov, V Y; Daminova, A G; Mikshina, P V; Petrova, O E; Ageeva, M V; Salnikov, V V; Gorshkova, T A; Gogolev, Y V

    2016-07-01

    Representatives of Pectobacterium genus are some of the most harmful phytopathogens in the world. In the present study, we have elucidated novel aspects of plant-Pectobacterium atrosepticum interactions. This bacterium was recently demonstrated to form specific 'multicellular' structures - bacterial emboli in the xylem vessels of infected plants. In our work, we showed that the process of formation of these structures includes the pathogen-induced reactions of the plant. The colonisation of the plant by P. atrosepticum is coupled with the release of a pectic polysaccharide, rhamnogalacturonan I, into the vessel lumen from the plant cell wall. This polysaccharide gives rise to a gel that serves as a matrix for bacterial emboli. P. atrosepticum-caused infection involves an increase of reactive oxygen species (ROS) levels in the vessels, creating the conditions for the scission of polysaccharides and modification of plant cell wall composition. Both the release of rhamnogalacturonan I and the increase in ROS precede colonisation of the vessels by bacteria and occur only in the primary xylem vessels, the same as the subsequent formation of bacterial emboli. Since the appearance of rhamnogalacturonan I and increase in ROS levels do not hamper the bacterial cells and form a basis for the assembly of bacterial emboli, these reactions may be regarded as part of the susceptible response of the plant. Bacterial emboli thus represent the products of host-pathogen integration, since the formation of these structures requires the action of both partners.

  9. Association between prenatal exposure to bacterial infection and risk of schizophrenia

    DEFF Research Database (Denmark)

    Mortensen, Erik Lykke; Sørensen, Holger J; Mortensen, Erik L;

    2009-01-01

    Recent research suggests that prenatal exposure to nonviral infection may be associated with increased risk of schizophrenia, and we hypothesized an association between maternal bacterial infection during pregnancy and elevated offspring risk of schizophrenia. Data on maternal infections from...... the Copenhagen Perinatal Cohort were linked with the Danish National Psychiatric Register. Offspring cases of narrowly defined schizophrenia (International Classification of Diseases, Eighth Revision [ICD-8]) and more broadly defined schizophrenia (ICD-8 and ICD-10) were identified before the ages of 32......-34 and 45-47 years, respectively. The effect of prenatal exposure to bacterial infections was adjusted for prenatal exposure to analgesics and parental social status. In a risk set of 7941 individuals, 85 cases (1.1%) of ICD-8 schizophrenia were identified by the age of 32-34 years and 153 cases (1...

  10. Skin, soft tissue and systemic bacterial infections following aquatic injuries and exposures.

    Science.gov (United States)

    Diaz, James H; Lopez, Fred A

    2015-03-01

    : Bacterial infections following aquatic injuries occur commonly in fishermen and vacationers after freshwater and saltwater exposures. Internet search engines were queried with the key words to describe the epidemiology, clinical manifestations, diagnostic and treatment strategies and outcomes of both the superficial and the deeper invasive infections caused by more common, newly emerging and unusual aquatic bacterial pathogens. Main findings included the following: (1) aquatic injuries often result in gram-negative polymicrobial infections with marine bacteria; (2) most marine bacteria are resistant to 1st- and 2nd-generation penicillins and cephalosporins; (3) nontuberculous, mycobacterial infections should be considered in late-onset, culture-negative and antibiotic-resistant marine infections; (4) superficial marine infections and pre-existing wounds exposed to seawater may result in deeply invasive infections and sepsis in immunocompromised patients. With the exception of minor marine wounds demonstrating localized cellulitis, most other marine infections and all gram-negative and mycobacterial marine infections will require therapy with antibiotic combinations.

  11. [Some immunological changes in children with bacterial infections treated with bacteriophages].

    Science.gov (United States)

    Pagava, K I; Metskhvarishvili, G D; Gachechiladze, K K; Korinteli, I A; Khoĭle, N; Dzuliashvili, M G

    2012-11-01

    The aim of the study was to reveal the possible immunological changes in children with bacterial infections treated with commercial bacteriophage preparations administered per os. In case of medical indications (for treatment or diagnostic) blood sampling was carried out. In serum the antibodies against bacteriophage preparations - phage cocktail components (phages against Staphylococcus, Streptococcus, Proteus vulgaris, Escherichia coli, Pseudomonas aeruginosa) were investigated. The neutralisation reaction was used. There were processed samples from 65 children with following diagnoses: sepsis, bacterial pneumonia, urinary tract infection, bacterial infections of upper respiratory ways, bacterial diarrhea. In samples taken in the first days of treatment antibodies were revealed in infants up to one month (I group) in 0/29 cases - 0%, in infants aged from one month till one year (II group)- 1/25 - 4.0%, in children aged from 1 till 15 years (III group) - 3/9 - 33.3%; data after 14-20 days from the beginning of treatment - I group - 0/9 - 0%, II group - 4/15 - 26.7%, III group - 5/5 - 100%; data after 30-60 days from the beginning of the treatment - I group - 1/5 - 20.0%, II group - 6/10 - 60.0%, III group - 3/3 - 100%. Bacteriophages neitralisation degree varied between 50,7% and 97.3%. Any regularity regarding different components of used phage preparations was not established. In case of inclusion of commercial phage preparations administered per os in the treatment of bacterial infections in children, the anti-phage neutralizing antibodies are produced by the macroorganism. This fact limits the duration of phage therapy and its usage in the treatment of future bacterial infections in treated patients. Production of anti-phage antibodies in young infants is substantially less expressed and this indicates to purposefulness and presumably higher efficacy of bacteriophage therapy in this age period.

  12. The balance of apoptotic and necrotic cell death in Mycobacterium tuberculosis infected macrophages is not dependent on bacterial virulence.

    Directory of Open Access Journals (Sweden)

    Rachel E Butler

    Full Text Available BACKGROUND: An important mechanism of Mycobacterium tuberculosis pathogenesis is the ability to control cell death pathways in infected macrophages: apoptotic cell death is bactericidal, whereas necrotic cell death may facilitate bacterial dissemination and transmission. METHODS: We examine M.tuberculosis control of spontaneous and chemically induced macrophage cell death using automated confocal fluorescence microscopy, image analysis, flow cytometry, plate-reader based vitality assays, and M.tuberculosis strains including H37Rv, and isogenic virulent and avirulent strains of the Beijing lineage isolate GC1237. RESULTS: We show that bacterial virulence influences the dynamics of caspase activation and the total level of cytotoxicity. We show that the powerful ability of M.tuberculosis to inhibit exogenously stimulated apoptosis is abrogated by loss of virulence. However, loss of virulence did not influence the balance of macrophage apoptosis and necrosis--both virulent and avirulent isogenic strains of GC1237 induced predominantly necrotic cell death compared to H37Rv which induced a higher relative level of apoptosis. CONCLUSIONS: This reveals that macrophage necrosis and apoptosis are independently regulated during M. tuberculosis infection of macrophages. Virulence affects the level of host cell death and ability to inhibit apoptosis but other strain-specific characteristics influence the ultimate mode of host cell death and alter the balance of apoptosis and necrosis.

  13. Gene expression in response to bacterial blight infection in rice

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@After a comprehensive screening of 47 rice lines inoculat_ed at different development stages with 7 different strains of Xanthomonas oryzae pv. oryzae , we selected 2 strains CR1 and CR7 from CNRRI,China. They gave a resistant and susceptible interaction respectively, when they were used to infect 15 d old seedlings of C101PKT.

  14. Healthcare-associated viral and bacterial infections in dentistry

    NARCIS (Netherlands)

    Laheij, A.M.G.A.; Kistler, J.O.; Belibasakis, G.N.; Valimaa, H.; de Soet, J.J.

    2012-01-01

    Infection prevention in dentistry is an important topic that has gained more interest in recent years and guidelines for the prevention of cross-transmission are common practice in many countries. However, little is known about the real risks of cross-transmission, specifically in the dental healthc

  15. Anaphylatoxins - Their role in bacterial infection and inflammation

    NARCIS (Netherlands)

    Haas, Pieter-Jan; van Strijp, Jos

    2007-01-01

    Activation of the complement system plays a crucial role in the pathogenesis of infection and inflammation. Especially the complement activation products C3a and C5a, known as the anaphylatoxins, are potent proinflammatory mediators. In addition to their evident role in innate immunity, it is clear

  16. Clavanin A improves outcome of complications from different bacterial infections.

    Science.gov (United States)

    Silva, Osmar N; Fensterseifer, Isabel C M; Rodrigues, Elaine A; Holanda, Hortência H S; Novaes, Natasha R F; Cunha, Junia P A; Rezende, Taia M B; Magalhães, Kelly G; Moreno, Susana E; Jerônimo, Márcio S; Bocca, Anamélia L; Franco, Octavio L

    2015-03-01

    The rapid increase in the incidence of multidrug-resistant infections today has led to enormous interest in antimicrobial peptides (AMPs) as suitable compounds for developing unusual antibiotics. In this study, clavanin A, an antimicrobial peptide previously isolated from the marine tunicate Styela clava, was selected as a purposeful molecule that could be used in controlling infection and further synthesized. Clavanin A was in vitro evaluated against Staphylococcus aureus and Escherichia coli as well as toward L929 mouse fibroblasts and skin primary cells (SPCs). Moreover, this peptide was challenged here in an in vivo wound and sepsis model, and the immune response was also analyzed. Despite displaying clear in vitro antimicrobial activity toward Gram-positive and -negative bacteria, clavanin A showed no cytotoxic activities against mammalian cells, and in acute toxicity tests, no adverse reaction was observed at any of the concentrations. Moreover, clavanin A significantly reduced the S. aureus CFU in an experimental wound model. This peptide also reduced the mortality of mice infected with E. coli and S. aureus by 80% compared with that of control animals (treated with phosphate-buffered saline [PBS]): these data suggest that clavanin A prevents the start of sepsis and thereby reduces mortality. These data suggest that clavanin A is an AMP that could improve the development of novel peptide-based strategies for the treatment of wound and sepsis infections.

  17. Procalcitonin Identifies Cell Injury, Not Bacterial Infection, in Acute Liver Failure.

    Directory of Open Access Journals (Sweden)

    Jody A Rule

    Full Text Available Because acute liver failure (ALF patients share many clinical features with severe sepsis and septic shock, identifying bacterial infection clinically in ALF patients is challenging. Procalcitonin (PCT has proven to be a useful marker in detecting bacterial infection. We sought to determine whether PCT discriminated between presence and absence of infection in patients with ALF.Retrospective analysis of data and samples of 115 ALF patients from the United States Acute Liver Failure Study Group randomly selected from 1863 patients were classified for disease severity and ALF etiology. Twenty uninfected chronic liver disease (CLD subjects served as controls.Procalcitonin concentrations in most samples were elevated, with median values for all ALF groups near or above a 2.0 ng/mL cut-off that generally indicates severe sepsis. While PCT concentrations increased somewhat with apparent liver injury severity, there were no differences in PCT levels between the pre-defined severity groups-non-SIRS and SIRS groups with no documented infections and Severe Sepsis and Septic Shock groups with documented infections, (p = 0.169. PCT values from CLD patients differed from all ALF groups (median CLD PCT value 0.104 ng/mL, (p ≤0.001. Subjects with acetaminophen (APAP toxicity, many without evidence of infection, demonstrated median PCT >2.0 ng/mL, regardless of SIRS features, while some culture positive subjects had PCT values <2.0 ng/mL.While PCT appears to be a robust assay for detecting bacterial infection in the general population, there was poor discrimination between ALF patients with or without bacterial infection presumably because of the massive inflammation observed. Severe hepatocyte necrosis with inflammation results in elevated PCT levels, rendering this biomarker unreliable in the ALF setting.

  18. Fluorescence in situ hybridization for the tissue detection of bacterial pathogens associated with porcine infections

    DEFF Research Database (Denmark)

    Jensen, Henrik Elvang; Jensen, Louise Kruse; Barington, Kristiane

    2015-01-01

    sequences within intact cells. FISH allows direct histological localization of the bacteria in the tissue and thereby a correlation between the infection and the histopathological changes present. This chapter presents protocols for FISH identification of bacterial pathogens in fixed deparaffinized tissue......Fluorescence in situ hybridization (FISH) is an efficient technique for the identification of specific bacteria in tissue of both experimental and spontaneous infections. The method detects specific sequences of nucleic acids by hybridization of fluorescently labeled probes to complementary target...

  19. Salmonella plasmid virulence gene spvB enhances bacterial virulence by inhibiting autophagy in a zebrafish infection model.

    Science.gov (United States)

    Li, Yuan-Yuan; Wang, Ting; Gao, Song; Xu, Guang-Mei; Niu, Hua; Huang, Rui; Wu, Shu-Yan

    2016-02-01

    Salmonella enterica serovar typhimurium (S. typhimurium) is a facultative intracellular pathogen that can cause gastroenteritis and systemic infection in a wide range of hosts. Salmonella plasmid virulence gene spvB is closely related to bacterial virulence in different cells and animal models, and the encoded protein acts as an intracellular toxin required for ADP-ribosyl transferase activity. However, until now there is no report about the pathogenecity of spvB gene on zebrafish. Due to the outstanding advantages of zebrafish in analyzing bacteria-host interactions, a S. typhimurium infected zebrafish model was set up here to study the effect of spvB on autophagy and intestinal pathogenesis in vivo. We found that spvB gene could decrease the LD50 of S. typhimurium, and the strain carrying spvB promoted bacterial proliferation and aggravated the intestinal damage manifested by the narrowed intestines, fallen microvilli, blurred epithelium cell structure and infiltration of inflammatory cells. Results demonstrated the enhanced virulence induced by spvB in zebrafish. In spvB-mutant strain infected zebrafish, the levels of Lc3 turnover and Beclin1 expression increased, and the double-membraned autophagosome structures were observed, suggesting that spvB can inhibit autophagy activity. In summary, our results indicate that S. typhimurium strain containing spvB displays more virulence, triggering an increase in bacterial survival and intestine injuries by suppressing autophagy for the first time. This model provides novel insights into the role of Salmonella plasmid virulence gene in bacterial pathogenesis, and can help to further elucidate the relationship between bacteria and host immune response.

  20. Synthetic furanones inhibit quorum-sensing and enhance bacterial clearance in Pseudomonas aeruginosa lung infection in mice

    DEFF Research Database (Denmark)

    Wu, H.; Song, Z.; Hentzer, Morten;

    2004-01-01

    Introduction: Antibiotics are used to treat bacterial infections by killing the bacteria or inhibiting their growth, but resistance to antibiotics can develop readily. The discovery that bacterial quorum-sensing regulates bacterial virulence as well as the formation of biofilms opens up new ways...

  1. Staphylococcus aureus - induced tumor necrosis factor - related apoptosis - inducing ligand expression mediates apoptosis and caspase-8 activation in infected osteoblasts

    Directory of Open Access Journals (Sweden)

    Bost Kenneth L

    2003-04-01

    Full Text Available Abstract Background Staphylococcus aureus infection of normal osteoblasts induces expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL. Results Normal osteoblasts were incubated in the presence of purified bacterial products over a range of concentrations. Results demonstrate that purified surface structures and a selected superantigen present in the extracellular environment are not capable of inducing TRAIL expression by osteoblasts. Osteoblasts were co-cultured with S. aureus at various multiplicities of infection utilizing cell culture chamber inserts. Results of those experiments suggest that direct contact between bacteria and osteoblasts is necessary for optimal TRAIL induction. Finally, S. aureus infection of osteoblasts in the presence of anti-TRAIL antibody demonstrates that TRAIL mediates caspase-8 activation and apoptosis of infected cells. Conclusions Collectively, these findings suggest a mechanism whereby S. aureus mediates bone destruction via induction of osteoblast apoptosis.

  2. Phenotypic T cell exhaustion in a murine model of bacterial infection in the setting of pre-existing malignancy.

    Directory of Open Access Journals (Sweden)

    Rohit Mittal

    Full Text Available While much of cancer immunology research has focused on anti-tumor immunity both systemically and within the tumor microenvironment, little is known about the impact of pre-existing malignancy on pathogen-specific immune responses. Here, we sought to characterize the antigen-specific CD8+ T cell response following a bacterial infection in the setting of pre-existing pancreatic adenocarcinoma. Mice with established subcutaneous pancreatic adenocarcinomas were infected with Listeria monocytogenes, and antigen-specific CD8+ T cell responses were compared to those in control mice without cancer. While the kinetics and magnitude of antigen-specific CD8+ T cell expansion and accumulation was comparable between the cancer and non-cancer groups, bacterial antigen-specific CD8+ T cells and total CD4+ and CD8+ T cells in cancer mice exhibited increased expression of the coinhibitory receptors BTLA, PD-1, and 2B4. Furthermore, increased inhibitory receptor expression was associated with reduced IFN-γ and increased IL-2 production by bacterial antigen-specific CD8+ T cells in the cancer group. Taken together, these data suggest that cancer's immune suppressive effects are not limited to the tumor microenvironment, but that pre-existing malignancy induces phenotypic exhaustion in T cells by increasing expression of coinhibitory receptors and may impair pathogen-specific CD8+ T cell functionality and differentiation.

  3. Widespread bacterial infection affecting Rana temporaria tadpoles in mountain areas

    Directory of Open Access Journals (Sweden)

    Rocco Tiberti

    2011-06-01

    Full Text Available Periodic mass die-offs of Rana temporaria tadpole populations have occurred in the ponds of prealpine mountain areas of Brescia (northern Italy since the early 2000s. The author reports some observational data and analytical results from three sites: tadpoles from mortality events had erythema, especially on the legs, suggestive of septicemia. Bacterial culture of these tadpoles revealed Aeromonas hydrophila and Aeromonas sobria, two organisms often associated with Red leg disease. Egg mass counts from 29 pastureland ponds did not revealed breeding activity declines over five years in the Monte Guglielmo area. Aeromonas hydrophila and Aeromonas sobria usually behave as opportunistic bacteria that can become pathogenic after suppression of the immune system by endogenous or exogenous stressors. Thus, a plurality of environmental factors may contribute to mortality events; some of them are discussed, including loss of high altitude breeding ponds resulting in overcrowding and poor water quality in remaining ponds and the presence of other pathogens.

  4. Impact of bacterial infections on aging and cancer

    DEFF Research Database (Denmark)

    Strickertsson, Jesper A B; Madsen, Claus Desler; Rasmussen, Lene Juel

    2014-01-01

    The commensal floras that inhabit the gastrointestinal tract play critical roles in immune responses, energy metabolism, and even cancer prevention. Pathogenic and out of place commensal bacteria, can however have detrimental effects on the host, by introducing genomic instability and mitochondri...... infections impact DNA repair and damage, and the consequence on the mitochondrial and nuclear genomes. We argue that in the gastrointestinal tract, these mechanisms can contribute to tumorigenesis as well as cellular aging of the digestive system....

  5. Hypovitaminosis A coupled to secondary bacterial infection in beef cattle

    Directory of Open Access Journals (Sweden)

    He Xiuyuan

    2012-11-01

    Full Text Available Abstract Background Vitamin A is essential for normal growth, development, reproduction, cell proliferation, cell differentiation, immune function and vision. Hypovitaminosis A can lead to a series of pathological damage in animals. This report describes the case of hypovitaminosis A associated with secondary complications in calves. Case presentation From February to March in 2011, 2-and 3-month old beef calves presented with decreased eyesight, apparent blindness and persistent diarrhea occurred in a cattle farm of Hubei province, China. Based on history inspection and clinical observation, we made a tentative diagnosis of hypovitaminosis A. The disease was confirmed as a congenital vitamin A deficiency by determination of the concentrations of vitamin A in serum and feed samples. Furthermore, pathological and microbiological examination showed that the disease was associated with pathogenic Escherichia coli (E. coli infection and mucosal barriers damage in intestines. The corresponding treatments were taken immediately, and the disease was finally under control for a month. Conclusions To our knowledge, this is the first report of hypovitaminosis A coupled to secondary infection of E. coli in beef cattle, advancing our knowledge of how vitamin A affects infection and immunity in animals. This study could also be contributed to scientific diagnosis and treatments of complex hypovitaminosis A in cattle.

  6. Bacterial lipoprotein-induced tolerance is reversed by overexpression of IRAK-1.

    LENUS (Irish Health Repository)

    Li, Chong Hui

    2012-03-01

    Tolerance to bacterial cell wall components including bacterial lipoprotein (BLP) represents an essential regulatory mechanism during bacterial infection. Reduced Toll-like receptor 2 (TLR2) and IL-1 receptor-associated kinase 1 (IRAK-1) expression is a characteristic of the downregulated TLR signaling pathway observed in BLP-tolerised cells. In this study, we attempted to clarify whether TLR2 and\\/or IRAK-1 are the key molecules responsible for BLP-induced tolerance. Transfection of HEK293 cells and THP-1 cells with the plasmid encoding TLR2 affected neither BLP tolerisation-induced NF-κB deactivation nor BLP tolerisation-attenuated pro-inflammatory cytokine tumor necrosis factor alpha (TNF-α) production, indicating that BLP tolerance develops despite overexpression of TLR2 in these cells. In contrast, overexpression of IRAK-1 reversed BLP-induced tolerance, as transfection of IRAK-1 expressing vector resulted in a dose-dependent NF-κB activation and TNF-α release in BLP-tolerised cells. Furthermore, BLP-tolerised cells exhibited markedly repressed NF-κB p65 phosphorylation and impaired binding of p65 to several pro-inflammatory cytokine gene promoters including TNF-α and interleukin-6 (IL-6). Overexpression of IRAK-1 restored the nuclear transactivation of p65 at both TNF-α and IL-6 promoters. These results indicate a crucial role for IRAK-1 in BLP-induced tolerance, and suggest IRAK-1 as a potential target for manipulation of the TLR-mediated inflammatory response during microbial sepsis.

  7. 78 FR 63220 - Guidance for Industry on Acute Bacterial Skin and Skin Structure Infections: Developing Drugs for...

    Science.gov (United States)

    2013-10-23

    ... HUMAN SERVICES Food and Drug Administration Guidance for Industry on Acute Bacterial Skin and Skin Structure Infections: Developing Drugs for Treatment; Availability AGENCY: Food and Drug Administration, HHS... guidance for industry entitled ``Acute Bacterial Skin and Skin Structure Infections: Developing Drugs...

  8. Acute bacterial infections of the lower respiratory tract in children from low-income countries

    NARCIS (Netherlands)

    Fleer, A; Wolf, B.H.M.

    2000-01-01

    Acute bacterial infection of the lower respiratory tract is a major cause of morbidity and mortality in children and is responsible for 4 million childhood deaths each year. Most of these deaths are caused by pneumonia and occur in the youngest children in the poorest parts of the world. Severe pneu

  9. Duration of fever and serious bacterial infections in children : a systematic review

    NARCIS (Netherlands)

    Elshout, Gijs; Monteny, Miriam; van der Wouden, Johannes C.; Koes, Bart W.; Berger, Marjolein Y.

    2011-01-01

    Background: Parents of febrile children frequently contact primary care. Longer duration of fever has been related to increased risk for serious bacterial infections (SBI). However, the evidence for this association remains controversial. We assessed the predictive value of duration of fever for SBI

  10. Primary role of electron work function for evaluation of nanostructured titania implant surface against bacterial infection.

    Science.gov (United States)

    Golda-Cepa, M; Syrek, K; Brzychczy-Wloch, M; Sulka, G D; Kotarba, A

    2016-09-01

    The electron work function as an essential descriptor for the evaluation of metal implant surfaces against bacterial infection is identified for the first time. Its validity is demonstrated on Staphylococcus aureus adhesion to nanostructured titania surfaces. The established correlation: work function-bacteria adhesion is of general importance since it can be used for direct evaluation of any electrically conductive implant surfaces.

  11. Study of Bacterial Samples Using Laser Induced Breakdown Spectroscopy

    Science.gov (United States)

    W, A. Farooq; M, Atif; W, Tawfik; M, S. Alsalhi; Z, A. Alahmed; M, Sarfraz; J, P. Singh

    2014-12-01

    Laser-induced breakdown spectroscopy (LIBS) technique has been applied to investigate two different types of bacteria, Escherichia coli (B1) and Micrococcus luteus (B2) deposited on glass slides using Spectrolaser 7000. LIBS spectra were analyzed using spectrolaser software. LIBS spectrum of glass substrate was compared with bacteria spectra. Ca, Mg, Na, K, P, S, Cl, Fe, Al, Mn, Cu, C, H and CN-band appeared in bacterial samples in air. Two carbon lines at 193.02 nm, 247.88 nm and one hydrogen line at 656.28 nm with intensity ratios of 1.9, 1.83 and 1.53 appeared in bacterial samples B1 and B2 respectively. Carbon and hydrogen are the important components of the bio-samples like bacteria and other cancer cells. Investigation on LIBS spectra of the samples in He and Ar atmospheres is also presented. Ni lines appeared only in B2 sample in Ar atmosphere. From the present experimental results we are able to show that LIBS technique has a potential in the identification and discrimination of different types of bacteria.

  12. Besifloxacin: a novel anti-infective for the treatment of bacterial conjunctivitis

    Directory of Open Access Journals (Sweden)

    Timothy L Comstock

    2010-03-01

    Full Text Available Timothy L Comstock1, Paul M Karpecki2, Timothy W Morris3, Jin-Zhong Zhang41Global Medical Affairs, Pharmaceuticals, Bausch and Lomb, Inc., Rochester, NY, USA; 2Koffler Vision Group, Lexington, KY, USA; 3Research and Development Microbiology and Sterilization Sciences, Bausch and Lomb, Inc., Rochester, NY, USA; 4Global Preclinical Development, Bausch and Lomb, Inc., Rochester, NY, USAAbstract: Bacterial conjunctivitis, commonly known as pink eye, is demographically unbiased in its prevalence and can be caused by a variety of aerobic and anaerobic bacteria. Timely empiric treatment with a broad-spectrum anti-infective, such as a topical fluoroquinolone, is critical in preventing potentially irreversible ocular damage. However, the rise in ocular methicillin-resistant Staphylococcus aureus isolates and the patterns of fluoroquinolone resistance for patients with other ocular bacterial infections mandate the need for new agents targeted for ocular use. Besifloxacin, a novel broad-spectrum fluoroquinolone, is approved for the treatment of bacterial conjunctivitis. It has a uniquely balanced dual-targeting activity that inhibits both DNA gyrase and topoisomerase IV and is associated with a lower incidence of resistance development. Besifloxacin is not marketed in other formulations, ensuring that its exposure is limited to bacterial populations in and around the eye. This specifically precludes any bacterial exposure to besifloxacin resulting from systemic use, which further reduces the likelihood of emergence of bacterial resistance. In vitro, besifloxacin has demonstrated equivalent or superior activity compared with other commonly used topical antibiotics. In clinical trials, besifloxacin has consistently demonstrated efficacy and safety in the treatment of patients with bacterial conjunctivitis. Besifloxacin is considered safe and is well tolerated with no observed contraindications.Keywords: conjunctivitis, fluoroquinolones, besifloxacin

  13. Autophagy and bacterial infection: an evolving arms race.

    Science.gov (United States)

    Choy, Augustine; Roy, Craig R

    2013-09-01

    Autophagy is an important membrane transport pathway that is conserved among eukaryotic cells. Although first described as an intracellular catabolic pathway used to break down self-components, autophagy has been found to play an important role in the elimination of intracellular pathogens. A variety of host mechanisms exist for recognizing and targeting intracellular bacteria to autophagosomes. Several intracellular bacteria have evolved ways to manipulate, inhibit, or avoid autophagy in order to survive in the cell. Thus, the autophagy pathway can be viewed as an evolutionarily conserved host response to infection.

  14. Respirable bacteriophages for the treatment of bacterial lung infections.

    Science.gov (United States)

    Hoe, Susan; Semler, Diana D; Goudie, Amanda D; Lynch, Karlene H; Matinkhoo, Sadaf; Finlay, Warren H; Dennis, Jonathan J; Vehring, Reinhard

    2013-12-01

    This review article discusses the development of respiratory therapeutics containing bacteriophages indicated for lung infections, specifically those that have become increasingly difficult to treat because of antibiotic resistance. Recent achievements and remaining problems are presented for each step necessary to develop a bacteriophage-containing dosage form for respiratory drug delivery, including selection of appropriate bacteriophages for therapy, processing and purification of phage preparations, formulation into a stable, solid dosage form, and delivery device selection. Safety and efficacy studies in animals and human subjects are also reviewed.

  15. Septic Pulmonary Embolism Induced by Dental Infection

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    Watanabe,Yoichi

    2013-08-01

    Full Text Available Dental infection can be an important source for septic pulmonary embolism (SPE, but only a few cases of SPE accompanying dental infection have been reported. The aim of this study was to characterize the clinical features of SPE induced by dental infection. Patients who fulfilled the diagnostic criteria described in the text were recruited in a retrospective fashion. All 9 patients were men, with a median age of 59 years (range:47 to 74 years. Eight patients had chest pain (88.9%, 5 had a preceding toothache (55.6% and 3 had preceding gingival swelling (33.3%. Blood cultures obtained from 7 patients were negative. Periodontitis was found in all of the cases, periapical periodontitis in 5 cases, and gingival abscess in 3 cases. The median duration of hospitalization was 15 days, and symptoms were mild in some cases. In addition to antimicrobial therapy, tooth extraction was performed in 3 cases, tooth scaling in 6. SPE induced by dental infection has prominent clinical characteristics such as male preponderance, chest pain, preceding toothache, and mild clinical course.

  16. Bacterial Infection Increases Reproductive Investment in Burying Beetles

    Science.gov (United States)

    Reavey, Catherine E.; Silva, Farley W. S.; Cotter, Sheena C.

    2015-01-01

    The Nicrophorus genus lives and breeds in a microbe rich environment. As such, it would be expected that strategies should be in place to counter potentially negative effects of the microbes common to this environment. In this study, we show the response of Nicrophorus vespilloides to the common soil bacterium, Bacillus subtilis. Phenoloxidase (PO) levels are not upregulated in response to the challenge and the bacteria are observed to multiply within the haemolymph of the host. Despite the growth of B. subtilis, survival is not affected, either in virgin or in breeding beetles. Some limit on bacterial growth in the haemolymph does seem to be occurring, suggesting mechanisms of resistance, in addition to tolerance mechanisms. Despite limited detrimental effects on the individual, the challenge by Bacillus subtilis appears to act as a cue to increase reproductive investment. The challenge may indicate a suite of negative environmental conditions that could compromise future breeding opportunities. This could act as a cue to increase parental investment in the current bout. PMID:26529021

  17. RIG-I detects infection with live Listeria by sensing secreted bacterial nucleic acids

    Science.gov (United States)

    Abdullah, Zeinab; Schlee, Martin; Roth, Susanne; Mraheil, Mobarak Abu; Barchet, Winfried; Böttcher, Jan; Hain, Torsten; Geiger, Sergej; Hayakawa, Yoshihiro; Fritz, Jörg H; Civril, Filiz; Hopfner, Karl-Peter; Kurts, Christian; Ruland, Jürgen; Hartmann, Gunther; Chakraborty, Trinad; Knolle, Percy A

    2012-01-01

    Immunity against infection with Listeria monocytogenes is not achieved from innate immune stimulation by contact with killed but requires viable Listeria gaining access to the cytosol of infected cells. It has remained ill-defined how such immune sensing of live Listeria occurs. Here, we report that efficient cytosolic immune sensing requires access of nucleic acids derived from live Listeria to the cytoplasm of infected cells. We found that Listeria released nucleic acids and that such secreted bacterial RNA/DNA was recognized by the cytosolic sensors RIG-I, MDA5 and STING thereby triggering interferon β production. Secreted Listeria nucleic acids also caused RIG-I-dependent IL-1β-production and inflammasome activation. The signalling molecule CARD9 contributed to IL-1β production in response to secreted nucleic acids. In conclusion, cytosolic recognition of secreted bacterial nucleic acids by RIG-I provides a mechanistic explanation for efficient induction of immunity by live bacteria. PMID:23064150

  18. Finding immune gene expression differences induced by marine bacterial pathogens in the Deep-sea hydrothermal vent mussel Bathymodiolus azoricus

    Science.gov (United States)

    Martins, E.; Queiroz, A.; Serrão Santos, R.; Bettencourt, R.

    2013-11-01

    The deep-sea hydrothermal vent mussel Bathymodiolus azoricus lives in a natural environment characterised by extreme conditions of hydrostatic pressure, temperature, pH, high concentrations of heavy metals, methane and hydrogen sulphide. The deep-sea vent biological systems represent thus the opportunity to study and provide new insights into the basic physiological principles that govern the defense mechanisms in vent animals and to understand how they cope with microbial infections. Hence, the importance of understanding this animal's innate defense mechanisms, by examining its differential immune gene expressions toward different pathogenic agents. In the present study, B. azoricus mussels were infected with single suspensions of marine bacterial pathogens, consisting of Vibrio splendidus, Vibrio alginolyticus, or Vibrio anguillarum, and a pool of these Vibrio bacteria. Flavobacterium suspensions were also used as a non-pathogenic bacterium. Gene expression analyses were carried out using gill samples from infected animals by means of quantitative-Polymerase Chain Reaction aimed at targeting several immune genes. We also performed SDS-PAGE protein analyses from the same gill tissues. We concluded that there are different levels of immune gene expression between the 12 h to 24 h exposure times to various bacterial suspensions. Our results from qPCR demonstrated a general pattern of gene expression, decreasing from 12 h over 24 h post-infection. Among the bacteria tested, Flavobacterium is the bacterium inducing the highest gene expression level in 12 h post-infections animals. The 24 h infected animals revealed, however, greater gene expression levels, using V. splendidus as the infectious agent. The SDS-PAGE analysis also pointed at protein profile differences between 12 h and 24 h, particularly evident for proteins of 18-20 KDa molecular mass, where most dissimilarity was found. Multivariate analyses demonstrated that immune genes, as well as experimental

  19. Linezolid concentrations in infected soft tissue and bone following repetitive doses in diabetic patients with bacterial foot infections1

    OpenAIRE

    Traunmüller, Friederike; Schintler, Michael V.; Spendel, Stephan; Popovic, Martin; Mauric, Oliver; Scharnagl, Erwin; Joukhadar, Christian

    2010-01-01

    Abstract The present study aimed at assessing unbound extracellular concentrations of linezolid in inflamed soft tissue and bone of diabetic patients suffering from severe bacterial foot infections. Linezolid was administered intravenously twice daily at a dosage of 600mg. At steady-state conditions, the microdialysis technique was utilised to sample serially interstitial space fluid from inflamed subcutaneous adipose tissue and metatarsal bone from 0?8h post dose in three represen...

  20. Gut microbiota promote hematopoiesis to control bacterial infection.

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    Khosravi, Arya; Yáñez, Alberto; Price, Jeremy G; Chow, Andrew; Merad, Miriam; Goodridge, Helen S; Mazmanian, Sarkis K

    2014-03-12

    The commensal microbiota impacts specific immune cell populations and their functions at peripheral sites, such as gut mucosal tissues. However, it remains unknown whether gut microbiota control immunity through regulation of hematopoiesis at primary immune sites. We reveal that germ-free mice display reduced proportions and differentiation potential of specific myeloid cell progenitors of both yolk sac and bone marrow origin. Homeostatic innate immune defects may lead to impaired early responses to pathogens. Indeed, following systemic infection with Listeria monocytogenes, germ-free and oral-antibiotic-treated mice display increased pathogen burden and acute death. Recolonization of germ-free mice with a complex microbiota restores defects in myelopoiesis and resistance to Listeria. These findings reveal that gut bacteria direct innate immune cell development via promoting hematopoiesis, contributing to our appreciation of the deep evolutionary connection between mammals and their microbiota.

  1. Community acquired urinary tract infection: etiology and bacterial susceptibility

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    Dias Neto José Anastácio

    2003-01-01

    Full Text Available PURPOSE: Urinary tract infections (UTI are one of the most common infectious diseases diagnosed. UTI account for a large proportion of antibacterial drug consumption and have large socio-economic impacts. Since the majority of the treatments begins or is done completely empirically, the knowledge of the organisms, their epidemiological characteristics and their antibacterial susceptibility that may vary with time is mandatory. OBJECTIVE: The aim of this study was to report the prevalence of uropathogens and their antibiotic susceptibility of the community acquired UTI diagnosed in our institution and to provide a national data. METHODS: We analyzed retrospectively the results of urine cultures of 402 patients that had community acquired urinary tract infection in the year of 2003. RESULTS: The mean age of the patients in this study was 45.34 ± 23.56 (SD years. There were 242 (60.2% females and 160 (39.8% males. The most commonly isolated organism was Escherichia coli (58%. Klebsiella sp. (8.4% and Enterococcus sp.(7.9% were reported as the next most common organisms. Of all bacteria isolated from community acquired UTI, only 37% were sensitive to ampicillin, 51% to cefalothin and 52% to trimethoprim/sulfamethoxazole. The highest levels of susceptibility were to imipenem (96%, ceftriaxone (90%, amikacin (90%, gentamicin (88%, levofloxacin (86%, ciprofloxacin (73%, nitrofurantoin (77% and norfloxacin (75%. CONCLUSION: Gram-negative agents are the most common cause of UTI. Fluoroquinolones remains the choice among the orally administered antibiotics, followed by nitrofurantoin, second and third generation cephalosporins. For severe disease that require parenteral antibiotics the choice should be aminoglycosides, third generation cephalosporins, fluoroquinolones or imipenem, which were the most effective.

  2. Use of Multiplex PCR for Diagnosis of Bacterial Infection Respiratory Mixed

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    Al-ssum, R. M.

    2010-01-01

    Full Text Available Atypical bacteria grow very slowly in culture or they do not grow at all leading to delays in detection and diagnosis. PCR multiplex was performed on template DNAs extracted from seventy three collected specimens. Thirty seven showed positive indication for the presence of bacterial infection. The incidence of Mycoplasma pneumoniae, Chlamydia pneumonia and Legionella pneumophila as a single infecting agent was 31.5%, 27.5% and 20 % respectively. Dual agent infection caused by Mycoplasma + Chlamydia, Mycoplasma + Legionella and Legionella + Chlamydia was 24%, 20% and 15% respectively. Triple agent infection caused by Legionella + Mycoplasma + Chlamydia was 17.5%. The etiology of the infection was M. pneumoniae, L. pneumophila or C. pneumoniae as a single etiology or in combination of two or three organisms.

  3. Acute bacterial skin and skin structure infections in internal medicine wards: old and new drugs.

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    Falcone, Marco; Concia, Ercole; Giusti, Massimo; Mazzone, Antonino; Santini, Claudio; Stefani, Stefania; Violi, Francesco

    2016-08-01

    Skin and soft tissue infections (SSTIs) are a common cause of hospital admission among elderly patients, and traditionally have been divided into complicated and uncomplicated SSTIs. In 2010, the FDA provided a new classification of these infections, and a new category of disease, named acute bacterial skin and skin structure infections (ABSSSIs), has been proposed as an independent clinical entity. ABSSSIs include three entities: cellulitis and erysipelas, wound infections, and major cutaneous abscesses This paper revises the epidemiology of SSTIs and ABSSSIs with regard to etiologies, diagnostic techniques, and clinical presentation in the hospital settings. Particular attention is owed to frail patients with multiple comorbidities and underlying significant disease states, hospitalized on internal medicine wards or residing in nursing homes, who appear to be at increased risk of infection due to multi-drug resistant pathogens and treatment failures. Management of ABSSSIs and SSTIs, including evaluation of the hemodynamic state, surgical intervention and treatment with appropriate antibiotic therapy are extensively discussed.

  4. Candida albicans infection of Caenorhabditis elegans induces antifungal immune defenses.

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    Read Pukkila-Worley

    2011-06-01

    Full Text Available Candida albicans yeast cells are found in the intestine of most humans, yet this opportunist can invade host tissues and cause life-threatening infections in susceptible individuals. To better understand the host factors that underlie susceptibility to candidiasis, we developed a new model to study antifungal innate immunity. We demonstrate that the yeast form of C. albicans establishes an intestinal infection in Caenorhabditis elegans, whereas heat-killed yeast are avirulent. Genome-wide, transcription-profiling analysis of C. elegans infected with C. albicans yeast showed that exposure to C. albicans stimulated a rapid host response involving 313 genes (124 upregulated and 189 downregulated, ~1.6% of the genome many of which encode antimicrobial, secreted or detoxification proteins. Interestingly, the host genes affected by C. albicans exposure overlapped only to a small extent with the distinct transcriptional responses to the pathogenic bacteria Pseudomonas aeruginosa or Staphylococcus aureus, indicating that there is a high degree of immune specificity toward different bacterial species and C. albicans. Furthermore, genes induced by P. aeruginosa and S. aureus were strongly over-represented among the genes downregulated during C. albicans infection, suggesting that in response to fungal pathogens, nematodes selectively repress the transcription of antibacterial immune effectors. A similar phenomenon is well known in the plant immune response, but has not been described previously in metazoans. Finally, 56% of the genes induced by live C. albicans were also upregulated by heat-killed yeast. These data suggest that a large part of the transcriptional response to C. albicans is mediated through "pattern recognition," an ancient immune surveillance mechanism able to detect conserved microbial molecules (so-called pathogen-associated molecular patterns or PAMPs. This study provides new information on the evolution and regulation of the innate

  5. Plant-activated bacterial receptor adenylate cyclases modulate epidermal infection in the Sinorhizobium meliloti–Medicago symbiosis

    OpenAIRE

    Tian, Chang Fu; Garnerone, Anne-Marie; Mathieu-Demazière, Céline; Masson-Boivin, Catherine; Batut, Jacques

    2012-01-01

    Legumes and soil bacteria called rhizobia have coevolved a facultative nitrogen-fixing symbiosis. Establishment of the symbiosis requires bacterial entry via root hair infection threads and, in parallel, organogenesis of nodules that subsequently are invaded by bacteria. Tight control of nodulation and infection is required to maintain the mutualistic character of the interaction. Available evidence supports a passive bacterial role in nodulation and infection after the microsymbiont has trig...

  6. The diagnostic and prognostic accuracy of five markers of serious bacterial infection in Malawian children with signs of severe infection.

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    Enitan D Carrol

    Full Text Available BACKGROUND: Early recognition and prompt and appropriate antibiotic treatment can significantly reduce mortality from serious bacterial infections (SBI. The aim of this study was to evaluate the utility of five markers of infection: C-reactive protein (CRP, procalcitonin (PCT, soluble triggering receptor expressed on myeloid cells-1 (sTREM-1, CD163 and high mobility group box-1 (HMGB1, as markers of SBI in severely ill Malawian children. METHODOLOGY AND PRINCIPAL FINDINGS: Children presenting with a signs of meningitis (n = 282 or pneumonia (n = 95, were prospectively recruited. Plasma samples were taken on admission for CRP, PCT, sTREM-1 CD163 and HMGB1 and the performance characteristics of each test to diagnose SBI and to predict mortality were determined. Of 377 children, 279 (74% had SBI and 83 (22% died. Plasma CRP, PCT, CD163 and HMGB1 and were higher in HIV-infected children than in HIV-uninfected children (p<0.01. In HIV-infected children, CRP and PCT were higher in children with SBI compared to those with no detectable bacterial infection (p<0.0005, and PCT and CD163 were higher in non-survivors (p = 0.001, p = 0.05 respectively. In HIV-uninfected children, CRP and PCT were also higher in children with SBI compared to those with no detectable bacterial infection (p<0.0005, and CD163 was higher in non-survivors (p = 0.05. The best predictors of SBI were CRP and PCT, and areas under the curve (AUCs were 0.81 (95% CI 0.73-0.89 and 0.86 (95% CI 0.79-0.92 respectively. The best marker for predicting death was PCT, AUC 0.61 (95% CI 0.50-0.71. CONCLUSIONS: Admission PCT and CRP are useful markers of invasive bacterial infection in severely ill African children. The study of these markers using rapid tests in a less selected cohort would be important in this setting.

  7. The Diagnostic and Prognostic Accuracy of Five Markers of Serious Bacterial Infection in Malawian Children with Signs of Severe Infection

    Science.gov (United States)

    Carrol, Enitan D.; Mankhambo, Limangeni A.; Jeffers, Graham; Parker, Deborah; Guiver, Malcolm; Newland, Paul; Banda, Daniel L.; Molyneux, Elizabeth M.; Heyderman, Robert S.

    2009-01-01

    Background Early recognition and prompt and appropriate antibiotic treatment can significantly reduce mortality from serious bacterial infections (SBI). The aim of this study was to evaluate the utility of five markers of infection: C-reactive protein (CRP), procalcitonin (PCT), soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), CD163 and high mobility group box-1 (HMGB1), as markers of SBI in severely ill Malawian children. Methodology and Principal Findings Children presenting with a signs of meningitis (n = 282) or pneumonia (n = 95), were prospectively recruited. Plasma samples were taken on admission for CRP, PCT, sTREM-1 CD163 and HMGB1 and the performance characteristics of each test to diagnose SBI and to predict mortality were determined. Of 377 children, 279 (74%) had SBI and 83 (22%) died. Plasma CRP, PCT, CD163 and HMGB1 and were higher in HIV-infected children than in HIV-uninfected children (p<0.01). In HIV-infected children, CRP and PCT were higher in children with SBI compared to those with no detectable bacterial infection (p<0.0005), and PCT and CD163 were higher in non-survivors (p = 0.001, p = 0.05 respectively). In HIV-uninfected children, CRP and PCT were also higher in children with SBI compared to those with no detectable bacterial infection (p<0.0005), and CD163 was higher in non-survivors (p = 0.05). The best predictors of SBI were CRP and PCT, and areas under the curve (AUCs) were 0.81 (95% CI 0.73–0.89) and 0.86 (95% CI 0.79–0.92) respectively. The best marker for predicting death was PCT, AUC 0.61 (95% CI 0.50–0.71). Conclusions Admission PCT and CRP are useful markers of invasive bacterial infection in severely ill African children. The study of these markers using rapid tests in a less selected cohort would be important in this setting. PMID:19675669

  8. Salmonella typhimurium Invasion Induces Apoptosis in Infected Macrophages

    Science.gov (United States)

    Monack, Denise M.; Raupach, Barbel; Hromockyj, Alexander E.; Falkow, Stanley

    1996-09-01

    Invasive Salmonella typhimurium induces dramatic cytoskeletal changes on the membrane surface of mammalian epithelial cells and RAW264.7 macrophages as part of its entry mechanism. Noninvasive S. typhimurium strains are unable to induce this membrane ruffling. Invasive S. typhimurium strains invade RAW264.7 macrophages in 2 h with 7- to 10-fold higher levels than noninvasive strains. Invasive S. typhimurium and Salmonella typhi, independent of their ability to replicate intracellularly, are cytotoxic to RAW264.7 macrophages and, to a greater degree, to murine bone marrow-derived macrophages. Here, we show that the macrophage cytotoxicity mediated by invasive Salmonella is apoptosis, as shown by nuclear morphology, cytoplasmic vacuolization, and host cell DNA fragmentation. S. typhimurium that enter cells causing ruffles but are mutant for subsequent intracellular replication also initiate host cell apoptosis. Mutant S. typhimurium that are incapable of inducing host cell membrane ruffling fail to induce apoptosis. The activation state of the macrophage plays a significant role in the response of macrophages to Salmonella invasion, perhaps indicating that the signal or receptor for initiating programmed cell death is upregulated in activated macrophages. The ability of Salmonella to promote apoptosis may be important for the initiation of infection, bacterial survival, and escape of the host immune response.

  9. Surveillance of acute community acquired urinary tract bacterial infections

    Institute of Scientific and Technical Information of China (English)

    Sibanarayan Rath; Rabindra N. Padhy

    2015-01-01

    Objective: To record the antibiotic resistance of community acquired uropathogens over a period of 24 months (May 2011-April 2012). Methods: Urine samples from patients of outpatient department (OPD) were used for isolating urinary tract infection (UTI)-causing bacteria that were cultured on suitable selective media and identified by biochemical tests. Their antibiograms were ascertained by Kirby-Bauer’s disc diffusion method, using 17 antibiotics of 5 different classes. Results: From 2137 urine samples 1332 strains of pathogenic bacteria belonging to 11 species were isolated. Two Gram-positives, Staphylococcus aureus and Enterococcus faecalis and nine Gram-negatives, Acinetobacter baumannii, Citrobacter sp., Escherichia coli, Enterobacter aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris and Pseudomonas aeruginosa were isolated. Both S. aureus and E. faecalis were vancomycin resistant, and resistant-strains of all pathogens increased in each 6-month period of study. Particularly, all Gram-negatives were resistant to nitrofurantoin and co-trimoxazole, the most preferred antibiotics of empiric therapy for UTI, but were moderately resistant to gentamicin, ampicillin, amoxyclav, ofloxacin and gatifloxacin. Most Gram-negatives produced extended spectrum β-lactamase. Conclusions: It was concluded that periodic surveillance of pathogens is an essential corollary in effective health management in any country, as empiric therapy is a common/essential practice in effective clinical management.

  10. [Diversity of soil bacterial community in banana orchards infected with wilt disease].

    Science.gov (United States)

    Chen, Bo; Huang, Xiao; Liu, Xiao-yu; Zhou, Deng-bo; Tan, Xin; Gao, Zhu-fen; Zhang, Xi-yan; Qi, Chun-lin

    2013-08-01

    Six soil samples including 3 wilt disease-infected samples and 3 disease-free samples were collected from the banana orchards in 3 areas in Lingao County, Hainan Province of South China. The soil physical and chemical properties were determined by conventional methods, and the diversity of soil bacterial community was analyzed by terminal restriction fragment length polymorphism (T-RFLP). Then, the relationships between the soil bacterial community composition and the soil physical and chemical properties were investigated. In the same areas, most of the soil physical and chemical properties were poorer in disease-infected than in disease-free banana orchards, with the most obvious difference in soil available P content and pH. The T-RFLP analysis showed the diversity of soil bacterial community was richer in disease-infected than in disease-free banana orchards. The lengths of the dominant T-RFs in the 3 areas were 144, 147 and 233 bp, respectively. Through the comparison with phylogenetic assignment tool, it was deduced that the dominant species in the 3 areas were Bacillus subtilis, Staphylococcus and Eubacterium ruminantium. The distribution of most T-RFs was related to the soil alkaline hydrolyzable N, available K, available P and water content, and the relative abundance of most T-RFs was richer in disease-infected than in disease-free banana orchards.

  11. The importance of bacterial and viral infections associated with adult asthma exacerbations in clinical practice.

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    Motoyasu Iikura

    Full Text Available Viral infection is one of the risk factors for asthma exacerbation. However, which pathogens are related to asthma exacerbation in adults remains unclear.The relation between various infections and adult asthma exacerbations was investigated in clinical practice.The study subjects included 50 adult inpatients due to asthma exacerbations and 20 stable outpatients for comparison. The pathogens from a nasopharyngeal swab were measured by multiplex PCR analysis.Asthma exacerbations occurred after a common cold in 48 inpatients. The numbers of patients with viral, bacterial, or both infections were 16, 9, and 9, respectively. The dominant viruses were rhinoviruses, respiratory syncytial virus, influenza virus, and metapneumovirus. The major bacteria were S. pneumoniae and H. influenzae. Compared to pathogen-free patients, the patients with pathogens were older and non-atopic and had later onset of disease, lower FeNO levels, lower IgE titers, and a higher incidence of comorbid sinusitis, COPD, or pneumonia. Compared to stable outpatients, asthma exacerbation inpatients had a higher incidence of smoking and comorbid sinusitis, COPD, or pneumonia. Viruses were detected in 50% of stable outpatients, but a higher incidence of rhinovirus, respiratory syncytial virus, and metapneumovirus infections was observed in asthma exacerbation inpatients. H. influenzae was observed in stable asthmatic patients. Other bacteria, especially S. pneumoniae, were important in asthma exacerbation inpatients.Viral or bacterial infections were observed in 70% of inpatients with an asthma exacerbation in clinical practice. Infection with S. pneumoniae was related to adult asthma exacerbation.

  12. A new Polyherbal formulation to control bacterial enteritis in poultry: a case study in Salmonella enteritidis induced experimental model

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    K.K.Baishya

    Full Text Available An experiemental study was conducted in day old 150 VenCobb chicks to evaluate efficacy of polyherbal formulation in induced bacterial enteritis with Salmonella enteritidis. Birds were randomly divided into three groups: negative control, infected and untreated control & prophylactically treated group with AV/ADC/16 (14th-28th days. Salmonella infection was induced on day 21st. A significant decrease in overall growth, productivity, feed conversion and mortality was evident in untreated infected group in addition to severity of clinical signs. However, prophylactic administration of herbal formulation reduced mortality and clinical symptoms were mild to negligible. No negative effect on growth & performance was observed in treated group III. [Veterinary World 2008; 1(11.000: 333-334

  13. Asymptomatic cattle naturally infected with Mycobacterium bovis present exacerbated tissue pathology and bacterial dissemination.

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    Álvaro Menin

    Full Text Available Rational discovery of novel immunodiagnostic and vaccine candidate antigens to control bovine tuberculosis (bTB requires knowledge of disease immunopathogenesis. However, there remains a paucity of information on the Mycobacterium bovis-host immune interactions during the natural infection. Analysis of 247 naturally PPD+ M. bovis-infected cattle revealed that 92% (n = 228 of these animals were found to display no clinical signs, but presented severe as well as disseminated bTB-lesions at post-mortem examination. Moreover, dissemination of bTB-lesions positively correlated with both pathology severity score (Spearman r = 0.48; p<0.0001 and viable tissue bacterial loads (Spearman r = 0.58; p = 0.0001. Additionally, granuloma encapsulation negatively correlated with M. bovis growth as well as pathology severity, suggesting that encapsulation is an effective mechanism to control bacterial proliferation during natural infection. Moreover, multinucleated giant cell numbers were found to negatively correlate with bacterial counts (Spearman r = 0.25; p = 0.03 in lung granulomas. In contrast, neutrophil numbers in the granuloma were associated with increased M. bovis proliferation (Spearman r = 0.27; p = 0.021. Together, our findings suggest that encapsulation and multinucleated giant cells control M. bovis viability, whereas neutrophils may serve as a cellular biomarker of bacterial proliferation during natural infection. These data integrate host granuloma responses with mycobacterial dissemination and could provide useful immunopathological-based biomarkers of disease severity in natural infection with M. bovis, an important cattle pathogen.

  14. Isolation of bacteria causing secondary bacterial infection in the lesions of cutaneous leishmaniasis

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    Ziaie Hengameh

    2008-01-01

    Full Text Available Background: Cutaneous Leishmaniasis (CL is a parasitic disease characterized by single or multiple ulcerations. Secondary bacterial infection is one of the complications of the disease that can increase the tissue destruction and the resulting scar. Objective: To effectively determine the incidence of real secondary bacteria infection in cutaneous leishmaniasis, we designed the current study. Methods and Materials: This was a cross-sectional study performed in Skin Diseases and Leishmaniasis Research Centre, Isfahan, Iran. In this study, 854 patients with confirmed CL were enrolled. Samples were taken from all the patients. Sterile swaps were achieved for the ulcer exudates and scraping was used for nonulcerated lesions. All the samples were transferred to tryptic soy broth medium. After 24 h of incubation in 37°C, they were transferred to eosin methylene blue agar (EBM and blood agar. Laboratory tests were used to determine the species of bacteria. All of the collected data were analyzed by SPSS software and chi-square. Results: Among 854 patients with confirmed cutaneous leishmaniasis, 177 patients (20.7% had positive cultures for secondary bacterial infection. Bacteria isolated from the lesions were as follows: Staphylococcus aureus - 123 cases (69.4%, coagulase negative Staphylococcus - 41 cases (23.1%, E. coil - 7 cases (3.9%, Proteus - 3 cases (1.7% and Klebsiella - 3 cases (1.7%. Conclusions: The incidence of secondary bacterial infection in lesions of CL was 20.7%. The most common isolated pathogen was Staphylococcus aureus . The incidence of secondary bacterial infection was significantly more in the ulcerated lesions as compared with nonulcerated lesions ( P = 0.00001.

  15. Bacterial infections in Lilongwe, Malawi: aetiology and antibiotic resistance

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    Makoka Mwai H

    2012-03-01

    Full Text Available Abstract Background Life-threatening infections present major challenges for health systems in Malawi and the developing world because routine microbiologic culture and sensitivity testing are not performed due to lack of capacity. Use of empirical antimicrobial therapy without regular microbiologic surveillance is unable to provide adequate treatment in the face of emerging antimicrobial resistance. This study was conducted to determine antimicrobial susceptibility patterns in order to inform treatment choices and generate hospital-wide baseline data. Methods Culture and susceptibility testing was performed on various specimens from patients presenting with possible infectious diseases at Kamuzu Central Hospital, Lilongwe, Malawi. Results Between July 2006 and December 2007 3104 specimens from 2458 patients were evaluated, with 60.1% from the adult medical service. Common presentations were sepsis, meningitis, pneumonia and abscess. An etiologic agent was detected in 13% of patients. The most common organisms detected from blood cultures were Staphylococcus aureus, Escherichia coli, Salmonella species and Streptococcus pneumoniae, whereas Streptococcus pneumoniae and Cryptococcus neoformans were most frequently detected from cerebrospinal fluid. Haemophilus influenzae was rarely isolated. Resistance to commonly used antibiotics was observed in up to 80% of the isolates while antibiotics that were not commonly in use maintained susceptibility. Conclusions There is widespread resistance to almost all of the antibiotics that are empirically used in Malawi. Antibiotics that have not been widely introduced in Malawi show better laboratory performance. Choices for empirical therapy in Malawi should be revised accordingly. A microbiologic surveillance system should be established and prudent use of antimicrobials promoted to improve patient care.

  16. Anti-bacterial effects of enzymatically-isolated sialic acid from glycomacropeptide in a Helicobacter pylori-infected murine model

    Science.gov (United States)

    Noh, Hye-Ji; Koh, Hong Bum; Kim, Hee-Kyoung; Cho, Hyang Hyun

    2017-01-01

    BACKGROUND/OBJECTIVES Helicobacter pylori (H. pylori) colonization of the stomach mucosa and duodenum is the major cause of acute and chronic gastroduodenal pathology in humans. Efforts to find effective anti-bacterial strategies against H. pylori for the non-antibiotic control of H. pylori infection are urgently required. In this study, we used whey to prepare glycomacropeptide (GMP), from which sialic acid (G-SA) was enzymatically isolated. We investigated the anti-bacterial effects of G-SA against H. pylori in vitro and in an H. pylori-infected murine model. MATERIALS/METHODS The anti-bacterial activity of G-SA was measured in vitro using the macrodilution method, and interleukin-8 (IL-8) production was measured in H. pylori and AGS cell co-cultures by ELISA. For in vivo study, G-SA 5 g/kg body weight (bw)/day and H. pylori were administered to mice three times over one week. After one week, G-SA 5 g/kg bw/day alone was administered every day for one week. Tumor necrosis factor-α (TNF-α), IL-1β, IL-6, and IL-10 levels were measured by ELISA to determine the anti-inflammatory effects of G-SA. In addition, real-time PCR was performed to measure the genetic expression of cytotoxin-associated gene A (cagA). RESULTS G-SA inhibited the growth of H. pylori and suppressed IL-8 production in H. pylori and in AGS cell co-cultures in vitro. In the in vivo assay, administration of G-SA reduced levels of IL-1β and IL-6 pro-inflammatory cytokines whereas IL-10 level increased. Also, G-SA suppressed the expression of cagA in the stomach of H. pylori-infected mice. CONCLUSION G-SA possesses anti-H. pylori activity as well as an anti-H. pylori-induced gastric inflammatory effect in an experimental H. pylori-infected murine model. G-SA has potential as an alternative to antibiotics for the prevention of H. pylori infection and H. pylori-induced gastric disease prevention. PMID:28194260

  17. [Epidemiology of nosocomial bacterial infection in a neonatal intensive care unit in Morocco].

    Science.gov (United States)

    Maoulainine, F-M-R; Elidrissi, N-S; Chkil, G; Abba, F; Soraa, N; Chabaa, L; Amine, M; Aboussad, A

    2014-09-01

    In neonatal intensive care units, the incidence of nosocomial infection is high. This study aimed to determine the epidemiology of a nosocomial bacterial infection in the neonatal intensive care unit of Mohamed VI university hospital. A total of 702 newborns were included in this study. Of the 702 neonates studied, 91 had developed a nosocomial infection. The incidence rate was 13% and incidence density was 21.2 per 1000 patient-days. The types of infection were: bloodstream infections (89%), pneumonia (6.6%), meningitis (3.3%), and urinary tract infections (1.1%). Nosocomial infection was particularly frequent in cases of low birth weight, prematurity, young age at admission, umbilical venous catheter, and mechanical ventilation. Multiresistant bacteria included enterobacteria producing betalactamase (76.9%), especially enterobacteria that were dominated by Klebsiella pneumoniae (39.7%). The mortality rate was 52.7% in nosocomial infections, 19 (20.87%) of whom had septic shock. The results of this study show that nosocomial infection is an intrahospital health problem that could be remedied by a prevention strategy.

  18. Population pharmacokinetics of ceftaroline in patients with acute bacterial skin and skin structure infections or community-acquired bacterial pneumonia.

    Science.gov (United States)

    Van Wart, Scott A; Forrest, Alan; Khariton, Tatiana; Rubino, Christopher M; Bhavnani, Sujata M; Reynolds, Daniel K; Riccobene, Todd; Ambrose, Paul G

    2013-11-01

    Ceftaroline, the active form of ceftaroline fosamil, is a broad-spectrum cephalosporin antibiotic. A population pharmacokinetic (PPK) model for ceftaroline was developed in NONMEM® using data from 185 healthy subjects and 92 patients with acute bacterial skin and skin structure infection (ABSSSI). Data from 128 patients with community-acquired bacterial pneumonia (CABP) were used for external model validation. Healthy subjects received 50-2,000 mg ceftaroline fosamil via intravenous (IV) infusion over 1 hour or intramuscular (IM) injection q12h or q24h. ABSSSI and CABP patients received 600 mg of ceftaroline fosamil IV over 1 hour q12h. A three-compartment model with zero-order IV or parallel first-order IM input and first-order elimination described ceftaroline fosamil PK. A two-compartment model with first-order conversion of prodrug to ceftaroline and parallel linear and saturable elimination described ceftaroline PK. Creatinine clearance was the primary determinant of ceftaroline exposure. Good agreement between the observed data and both population (r(2)  = 0.93) and individual post-hoc (r(2)  = 0.98) predictions suggests the PPK model can adequately approximate ceftaroline PK using covariate information. Such a PPK model can evaluate dose adjustments for patients with renal impairment and generate ceftaroline exposures for use in pharmacokinetic-pharmacodynamic assessments of efficacy in patients with ABSSSI or CABP.

  19. Probiotic Activity of a Bacterial Strain Isolated from Ancient Permafrost Against Salmonella Infection in Mice.

    Science.gov (United States)

    Fursova, O; Potapov, V; Brouchkov, A; Pogorelko, G; Griva, G; Fursova, N; Ignatov, S

    2012-09-01

    Bacillus cereus strain F, collected from relict permafrost located in Siberia, was analyzed for probiotic activity in the mouse Salmonella enterica model. Viable bacterial cells were found in frozen soils taken at Mammoth Mountain in Yakutia from a depth below the level of seasonal thawing. Geological data indicated the absence of a thawing within millions of years of deposited soils, which helped to ensure the ancient origin of our sample. According to DNA analysis, bacterial cells collected from the relict permafrost appeared to be B. cereus strain F. The morphology of these bacteria was analyzed using atomic force microscopy. B. cereus strain F was assessed as a nonpathogenic bacterium by evaluation of its pathogenicity. A S. enterica model is described in mice after per oral inoculation and serves as a model for the human carrier state. Using this model, probiotic activity by the bacterial strain isolated from the ancient permafrost has been shown against Salmonella infection in mice.

  20. SECONDARY BACTERIAL INFECTION IN ADULT PATIENTS WITH PROLONGED AND SEVERE DENGUE FEVER

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    Anil Kumar

    2016-05-01

    Full Text Available INTRODUCTION Generally, in dengue shock syndrome antibiotics are not advised. But unrecognised bacterial infection is likely to contribute to morbidity and mortality, probably because of increased vascular permeability. OBJECTIVES To assess the incidence of secondary bacterial infection in adult patients with prolonged and severe dengue fever. METHODS A prospective study was conducted recruiting patients with confirmed acute dengue infection who had prolonged fever (>5 days. Prior to institution of antibiotic therapy, two sets of blood cultures were taken from patients. Demographic, clinical, haematological and biochemical parameters were recorded. Severity of fever & associated symptoms assessed. Ultrasonography done to find out development of ascites and pleural effusions. RESULTS Sixty patients (60.0% males with a mean age of 33.5 years (SD 12.1 were studied. The average duration of fever was 6.9 days (SD 1.6. Fifteen patients (25% had bacterial isolates in their blood cultures; Staphylococcus aureus (n=3, coliforms (n=7, pseudomonas (n=2 and 3 had mixed growths. The culture positive group had severe body aches and joints paint at admission and high grade fever, third space fluid accumulation and significant drop in platelets compared to culture-negative group. CONCLUSIONS A quarter of dengue patients with prolonged fever had a bacterial isolate. Culture-positive patients appeared more ill with body aches and had higher degrees of fever during the course of the illness. Increased vascular permeability may predispose to bacterial seepage into blood. Although white cell count is not helpful in detecting bacteraemia in dengue fever, low platelet count and severe symptoms at presentation may be helpful.

  1. Hindlimb suspension and SPE-like radiation impairs clearance of bacterial infections.

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    Minghong Li

    Full Text Available A major risk of extended space travel is the combined effects of weightlessness and radiation exposure on the immune system. In this study, we used the hindlimb suspension model of microgravity that includes the other space stressors, situational and confinement stress and alterations in food intake, and solar particle event (SPE-like radiation to measure the combined effects on the ability to control bacterial infections. A massive increase in morbidity and decrease in the ability to control bacterial growth was observed using 2 different types of bacteria delivered by systemic and pulmonary routes in 3 different strains of mice. These data suggest that an astronaut exposed to a strong SPE during extended space travel is at increased risk for the development of infections that could potentially be severe and interfere with mission success and astronaut health.

  2. Analysis of Gram-positive bacterial infection in patients following liver transplantation

    Institute of Scientific and Technical Information of China (English)

    LI Hong; YU De-lei; REN lei; ZHONG Lin; PENG Zhi-hai; TENG Mu-jian

    2012-01-01

    Background Liver transplantation is the most effective treatment for patients with end-stage liver failure,however infection after transplantation is a serious clinical complication.The purpose of this research was to investigate the molecular epidemiology and the influence of multidrug-resistant Gram-positive infection in patients,following liver transplantation,to provide reference for clinical treatment and prevention of Gram-positive bacterial infection.Methods We isolated and detected bacteria from phlegm,throat swabs,urine,wound or wound secretions,blood,and fecal samples from 221 liver transplant patients in our hospital from January 2007 to April 2010.All isolated bacterial strains were identified and tested by minimal inhibitory concentration (MIC) drug-sensitive detection using the BioMerieux ATB bacterial identification instrument and repetitive extragenic palindromic-polymerase chain reaction (REP-PCR)detection of bacterial homology.Risk factors were calculated by multivariate Logistic regression analysis.Results We collected 250 specimens from 221 patients hospitalized following liver transplantation surgery,of which 29patients developed multiple infections.Sixty-five Gram-positive bacterial strains were isolated from different specimens from 53 infectious patients.We detected 29 multidrug-resistant Gram-positive strains from 29 patients (44.62%),including 20 Staphylococcus aureus (S.aureus) strains (68.97%) and nine Enterococcus strains (31.03%).All 20 S.aureus strains were highly resistant to aminoglycosides (gentamicin),cephalosporins (cefoxitin),quinolones (ciprofloxacin and levofloxacin),lincomycins (clindamycin),penicillin,and erythromycin.The resistance rate reached 100% in some cases.The S.aureus strains were highly sensitive to vancomycin and oxazolidinone (linezolid),with MIC50 <2 μg/ml for both.The nine Enterococci strains were also highly resistant to aminoglycosides,quinolones,and penicillins,and highly sensitive to vancomycin

  3. Tissue characterization of skin ulcer for bacterial infection by multiple statistical analysis of echo amplitude envelope

    Science.gov (United States)

    Omura, Masaaki; Yoshida, Kenji; Kohta, Masushi; Kubo, Takabumi; Ishiguro, Toshimichi; Kobayashi, Kazuto; Hozumi, Naohiro; Yamaguchi, Tadashi

    2016-07-01

    To characterize skin ulcers for bacterial infection, quantitative ultrasound (QUS) parameters were estimated by the multiple statistical analysis of the echo amplitude envelope based on both Weibull and generalized gamma distributions and the ratio of mean to standard deviation of the echo amplitude envelope. Measurement objects were three rat models (noninfection, critical colonization, and infection models). Ultrasound data were acquired using a modified ultrasonic diagnosis system with a center frequency of 11 MHz. In parallel, histopathological images and two-dimensional map of speed of sound (SoS) were observed. It was possible to detect typical tissue characteristics such as infection by focusing on the relationship of QUS parameters and to indicate the characteristic differences that were consistent with the scatterer structure. Additionally, the histopathological characteristics and SoS of noninfected and infected tissues were matched to the characteristics of QUS parameters in each rat model.

  4. Role of the Inflammasome, IL-1β, and IL-18 in Bacterial Infections

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    Manoranjan Sahoo

    2011-01-01

    Full Text Available The inflammasome is an important innate immune pathway that regulates at least two host responses protective against infections: (1 secretion of the proinflammatory cytokines IL-1β and IL-18 and (2 induction of pyroptosis, a form of cell death. Inflammasomes, of which different types have been identified, are multiprotein complexes containing pattern recognition receptors belonging to the Nod-like receptor family or the PYHIN family and the protease caspase-1. The molecular aspects involved in the activation of different inflammasomes by various pathogens are being rapidly elucidated, and their role during infections is being characterized. Production of IL-1β and IL-18 and induction of pyroptosis of the infected cell have been shown to be protective against many infectious agents. Here, we review the recent literature concerning inflammasome activation in the context of bacterial infections and identify important questions to be answered in the future.

  5. Drosophila embryos as model systems for monitoring bacterial infection in real time.

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    Isabella Vlisidou

    2009-07-01

    Full Text Available Drosophila embryos are well studied developmental microcosms that have been used extensively as models for early development and more recently wound repair. Here we extend this work by looking at embryos as model systems for following bacterial infection in real time. We examine the behaviour of injected pathogenic (Photorhabdus asymbiotica and non-pathogenic (Escherichia coli bacteria and their interaction with embryonic hemocytes using time-lapse confocal microscopy. We find that embryonic hemocytes both recognise and phagocytose injected wild type, non-pathogenic E. coli in a Dscam independent manner, proving that embryonic hemocytes are phagocytically competent. In contrast, injection of bacterial cells of the insect pathogen Photorhabdus leads to a rapid 'freezing' phenotype of the hemocytes associated with significant rearrangement of the actin cytoskeleton. This freezing phenotype can be phenocopied by either injection of the purified insecticidal toxin Makes Caterpillars Floppy 1 (Mcf1 or by recombinant E. coli expressing the mcf1 gene. Mcf1 mediated hemocyte freezing is shibire dependent, suggesting that endocytosis is required for Mcf1 toxicity and can be modulated by dominant negative or constitutively active Rac expression, suggesting early and unexpected effects of Mcf1 on the actin cytoskeleton. Together these data show how Drosophila embryos can be used to track bacterial infection in real time and how mutant analysis can be used to genetically dissect the effects of specific bacterial virulence factors.

  6. Establishment of a Multiplex PCR System to Diagnose Tuberculosis and Other Bacterial Infections

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    In order to rapidly diagnose and differentiate tuberculosis from other bacterial infections, a 16S rRNA gene (16s rDNA)-directed multiplex PCR system was developed. In this system, a pair of universal primers and a tubercle bacillus (Tb)-specific primer were designed based on highly conserved regions and Tb species-specific variable region of bacterial 16s rDNA. A 360bp fragment was detected in all bacteria tested, and a 210bp fragment was found only in Tb. 19 species of known bacteria including Tb were used for evaluating specificity, universality and sensitivity of the PCR. Candida albicans and human diploid cell served as controls. It was found that both 210bp and 360bp fragments were amplified only in Tb, and only 360 bp fragment was detected in other 18 species of general bacteria. Candida albicans and human cells were negative for both 360bp and 210bp fragments.The lowest detectable level of the PCR was 10 fg of DNA for Escherichia coli and 100 fg of DNA for Tb. The results indicated that this multiplex PCR system for the simultaneous detection of Tb and other common bacteria had higher specificity and sensitivity, as well as good universality and might be useful to rapidly diagnose bacterial infections and effectively distinguish tuberculosis from other bacterial involvement.

  7. Platelet concentrates: reducing the risk of transfusion-transmitted bacterial infections

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    de Korte D

    2014-06-01

    Full Text Available Dirk de Korte,1 Jan H Marcelis2 1Department of Product and Process Development, Sanquin Blood Bank, Amsterdam, 2Department of Microbiology, St Elisabeth Hospital, Tilburg, the Netherlands Abstract: The introduction of a combination of interventions during collection of whole-blood or platelet concentrates has been successful in lowering the degree of bacterial contamination in the final product, the platelet concentrate, by 50%–75%. These interventions were improved donor questionnaires, best-practice skin disinfection, and diversion of first blood volume. These interventions have reduced the number of bacteria present in the platelet concentrates. In combination with screening for bacterial contamination of platelet concentrates with a culture method, the degree of transfusion-transmitted bacterial infection has been reduced significantly. Due to the very low initial bacteria counts upon collection of the products, the need for improved sensitivity of early screenings tests or highly selective point-of-issue tests remains. The latter should be rapid and easy to perform. An alternative approach might be the implementation of pathogen-inactivation methods for cellular blood products to reduce the amount of pathogens. However, these methods are costly, and so far not proved to be cost-effective, especially in countries with an already-low incidence of transfusion-transmitted infections by viruses, parasites, or bacteria. Keywords: blood products, bacterial contamination, screening, point of issue, pathogen inactivation

  8. Viral-bacterial co-infection in Australian Indigenous children with acute otitis media

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    Whiley David

    2011-06-01

    Full Text Available Abstract Background Acute otitis media with perforation (AOMwiP affects 40% of remote Indigenous children during the first 18 months of life. Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis are the primary bacterial pathogens of otitis media and their loads predict clinical ear state. Our hypothesis is that antecedent respiratory viral infection increases bacterial density and progression to perforation. Methods A total of 366 nasopharyngeal swabs from 114 Indigenous children were retrospectively examined. A panel of 17 respiratory viruses was screened by PCR, and densities of S. pneumoniae, H. influenzae and M. catarrhalis were estimated by quantitative real time PCR. Data are reported by clinical ear state. Results M. catarrhalis (96%, H. influenzae (91%, S. pneumoniae (89% and respiratory viruses (59% were common; including rhinovirus (HRV (38%, polyomavirus (HPyV (14%, adenovirus (HAdV (13%, bocavirus (HBoV (8% and coronavirus (HCoV (4%. Geometric mean bacterial loads were significantly higher in children with acute otitis media (AOM compared to children without evidence of otitis media. Children infected with HAdV were 3 times more likely (p Conclusion This study confirms a positive association between nasopharyngeal bacterial load and clinical ear state, exacerbated by respiratory viruses, in Indigenous children. HAdV was independently associated with acute ear states.

  9. Etiologic structure of bacterial intestinal infections in monkeys of Adler breeding center.

    Science.gov (United States)

    Ardasheliya, S N; Kalashnikova, V A; Dzhikidze, E K

    2011-10-01

    We studied etiologic structure of bacterial intestinal infections in monkeys of Adler nursery. A total of 533 monkeys with diarrhea syndrome and monkeys dead from intestinal infections, as well as clinically healthy monkeys and animals dead from other pathologies were examined by bacteriological and molecular-genetic methods. Pathogenic enterobacteria Shigella and Salmonella and microaerophile Campylobacter were found in 5 and 19%, respectively. A high percentage (49%) of intestinal diseases of unknown etiology was revealed in monkeys. The fact that the number of detected opportunistic enterobacteria did not differ in healthy and diseased monkeys suggests that they are not involved into the etiology of intestinal disease.

  10. Prevalence of Bacterial Urinary Tract Infections in Patients before and after of Kidney Transplantation

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    Esmaeili, R.

    2014-06-01

    Full Text Available Background and Objective: Urinary tract infections and bacteremia are the major problems in renal transplant patients, which are mostly due to immunesuppressive regimens, surgery, and exposure to the germs in hospital. The aim of this study was to determine the prevalence of bacterial agents in the blood and urine samples of kidney transplant candidates. Material and Methods: In this one-year-long study, thirty-three renal transplant candidates were assessed for urine and blood cultures. One urine and blood samples from each patient before transplantation and three samples after transplantation were collected. The Samples, using standard microbiological methods, were investigated and infectious organisms identified. Results: In 133 urine samples, Escherichia coli (20.5%, Enterobacter spp. (5.3%, Klebsiella spp. (3 % and Staphylococcus epidermidis (1.5% were isolated. In the blood samples, Enterobacter spp. (9.1%, Escherichia coli (6.8%, Staphylococcus epidermidis (3.8% and Klebsiella spp. (0.8% were isolated. Conclusion: The results indicate that urinary tract infection was high in patients with transplanted kidney, and E. coli is the most common cause of this infection. Keywords: Kidney Transplantation; Bacterial infections; Urinary Tract and Blood Infections; Escherichia Coli

  11. A novel outbred mouse model of 2009 pandemic influenza and bacterial co-infection severity.

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    Kevin J McHugh

    Full Text Available Influenza viruses pose a significant health risk and annually impose a great cost to patients and the health care system. The molecular determinants of influenza severity, often exacerbated by secondary bacterial infection, are largely unclear. We generated a novel outbred mouse model of influenza virus, Staphylococcus aureus, and co-infection utilizing influenza A/CA/07/2009 virus and S. aureus (USA300. Outbred mice displayed a wide range of pathologic phenotypes following influenza virus or co-infection ranging broadly in severity. Influenza viral burden positively correlated with weight loss although lung histopathology did not. Inflammatory cytokines including IL-6, TNF-α, G-CSF, and CXCL10 positively correlated with both weight loss and viral burden. In S. aureus infection, IL-1β, G-CSF, TNF-α, and IL-6 positively correlated with weight loss and bacterial burden. In co-infection, IL-1β production correlated with decreased weight loss suggesting a protective role. The data demonstrate an approach to identify biomarkers of severe disease and to understand pathogenic mechanisms in pneumonia.

  12. Allergic airway inflammation decreases lung bacterial burden following acute Klebsiella pneumoniae infection in a neutrophil- and CCL8-dependent manner.

    Science.gov (United States)

    Dulek, Daniel E; Newcomb, Dawn C; Goleniewska, Kasia; Cephus, Jaqueline; Zhou, Weisong; Reiss, Sara; Toki, Shinji; Ye, Fei; Zaynagetdinov, Rinat; Sherrill, Taylor P; Blackwell, Timothy S; Moore, Martin L; Boyd, Kelli L; Kolls, Jay K; Peebles, R Stokes

    2014-09-01

    The Th17 cytokines interleukin-17A (IL-17A), IL-17F, and IL-22 are critical for the lung immune response to a variety of bacterial pathogens, including Klebsiella pneumoniae. Th2 cytokine expression in the airways is a characteristic feature of asthma and allergic airway inflammation. The Th2 cytokines IL-4 and IL-13 diminish ex vivo and in vivo IL-17A protein expression by Th17 cells. To determine the effect of IL-4 and IL-13 on IL-17-dependent lung immune responses to acute bacterial infection, we developed a combined model in which allergic airway inflammation and lung IL-4 and IL-13 expression were induced by ovalbumin sensitization and challenge prior to acute lung infection with K. pneumoniae. We hypothesized that preexisting allergic airway inflammation decreases lung IL-17A expression and airway neutrophil recruitment in response to acute K. pneumoniae infection and thereby increases the lung K. pneumoniae burden. As hypothesized, we found that allergic airway inflammation decreased the number of K. pneumoniae-induced airway neutrophils and lung IL-17A, IL-17F, and IL-22 expression. Despite the marked reduction in postinfection airway neutrophilia and lung expression of Th17 cytokines, allergic airway inflammation significantly decreased the lung K. pneumoniae burden and postinfection mortality. We showed that the decreased lung K. pneumoniae burden was independent of IL-4, IL-5, and IL-17A and partially dependent on IL-13 and STAT6. Additionally, we demonstrated that the decreased lung K. pneumoniae burden associated with allergic airway inflammation was both neutrophil and CCL8 dependent. These findings suggest a novel role for CCL8 in lung antibacterial immunity against K. pneumoniae and suggest new mechanisms of orchestrating lung antibacterial immunity.

  13. Pathogen-Specific Local Immune Fingerprints Diagnose Bacterial Infection in Peritoneal Dialysis Patients

    OpenAIRE

    Lin, Chan-Yu; Roberts, Gareth W.; Kift-Morgan, Ann; Donovan, Kieron L.; Topley, Nicholas; Eberl, Matthias

    2013-01-01

    Accurate and timely diagnosis of bacterial infection is crucial for effective and targeted treatment, yet routine microbiological identification is inefficient and often delayed to an extent that makes it clinically unhelpful. The immune system is capable of a rapid, sensitive and specific detection of a broad spectrum of microbes, which has been optimized over millions of years of evolution. A patient's early immune response is therefore likely to provide far better insight into the true nat...

  14. DMPD: Role of Nods in bacterial infection. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available SVG File (.svg) HTML File (.html) CSML File (.csml) Open .csml file with CIOPlayer Open .csml file with CIO... 2007 Apr;9(5):629-36. Epub 2007 Jan 27. (.png) (.svg) (.html) (.csml) Show Role of Nods in bacterial infect...Player - ※CIO Playerのご利用上の注意 Open .csml file with CIO Open .csml file with CIO - ※CIOのご利用上の注意 ...

  15. Bacterial infection of mudfish Clarias gariepinus (Siluriformes: Clariidae) fingerlings in tropical nursery ponds.

    Science.gov (United States)

    Ikpi, Gabriel; Offem, Benedict

    2011-06-01

    Bacterial infection among the most common cultured mudfish Clarias gariepinus in Africa, has become a cause of concern, because it constitutes the largest economic loss in fish farms. In order to provide useful biological data of the pathogens for good management practices, samples were collected monthly between January 2008 and December 2009 in three monoculture nursery ponds, located in three different positions: upriver (A, grassland), mid-river (B, mixed forest and grassland) and downriver (C, rainforest) along 200 km length of Cross River floodplains, Nigeria. A total of 720 fingerlings between 15.1 and 20.7 g were analyzed to determine the degree of infection. The bacterial pathogens were taken from their external surfaces, and were isolated and identified by standard methods. The caudal fins of fingerlings from pond A had the highest bacterial load (5.8 x 10(3) cfu/g), while the least counts (1.2 x 103 cfu/g) were identified on the head of fish from pond C, with Flexibacter columnaris as the major etiological agent. Pseudomonas fluorescens, Aeromonas hydrophila, Escherichia coli, Staphylococcus aureus and Micrococcus luteus were identified as co-isolates with P. fluorescens as dominant (0.7 x 10(2) cfu/mL) co-isolates in pond water. Clinical signs of five white spots with red periphery appeared on the external surface of infected fish. All the fish sampled, died after 4 to 9 days. There was no significant difference in the bacterial counts between different ponds, but the difference between fish organs/parts examined was significant. Fish from these ponds are therefore potentially dangerous to consumers and highly devalued, with the economic impact to producers. Preventive methods to avoid these infections are recommended.

  16. Combining Flagellin and human β-defensin-3 to combat bacterial Infections

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    Ofra eSabag

    2014-12-01

    Full Text Available The discovery and therapeutic use of antibiotics made a major contribution to the reduction of human morbidity and mortality. However, the growing resistance to antibiotics has become a matter of huge concern. In this study we aimed to develop an innovative approach to treat bacterial infections utilizing two components: the human antibacterial peptide β-defensin-3 (BD3 and the bacterial protein flagellin (F. This combination was designed to provide an efficient weapon against bacterial infections with the peptide killing the bacteria directly, while the flagellin protein triggers the immune system and acts against bacteria escaping from the peptide’s action. We designed, expressed and purified the fusion protein FBD3 and its two components, the F protein and the native BD3 peptide. FBD3 fusion protein and native BD3 peptide had antibacterial activity in vitro against various bacterial strains. FBD3 and F proteins could also recognize their receptor expressed on target cells and stimulated secretion of IL-8. In addition, F and FBD3 proteins had a partial protective effect in mice infected by pathogenic E. coli bacteria that cause a lethal disease. Moreover, we were able to show partial protection of mice infected with E. coli using a flagellin sequence from Salmonella.We also explored flagellin’s basic mechanisms of action, focusing on its effects on CD4+ T cells from healthy donors. We found that F stimulation caused an increase in the mRNA levels of the Th1 response cytokines IL12A and IFNγ. In addition, F stimulation affected its own receptor.

  17. [The bacterial microflora of diabetic foot infection and factors determining its spectrum in Ouagadougou (Burkina Faso)].

    Science.gov (United States)

    Guira, O; Tiéno, H; Traoré, S; Diallo, I; Ouangré, E; Sagna, Y; Zabsonré, J; Yanogo, D; Traoré, S S; Drabo, Y J

    2015-12-01

    The aim of the study was to describe the bacterial microflora of diabetic foot infection and to identify the factors which determine the bacterial spectrum in order to increase empiric antibiotic prescription in Ouagadougou. The study was a cross-sectional one, carried from July 1st, 2011 to June 30, 2012 in the departments of internal medicine and general and digestive surgery in Yalgado Ouédraogo teaching hospital. Samples for bacteriological tests consisted of aspiration of pus through the healthy skin, curettage and swab of the base of the ulceration or tissue biopsy from foot lesions. The bacteria's sensitivity to antibiotics has been tested by the qualitative method (Kirby-Bauer). The frequency of diabetic foot infection was 14.45% and the monthly incidence 5.33. The mean age of patients was 56 years and the sex ratio 1.37. Foot ulcerations were chronic in 33 (51.56%), necrotic in 51 (79.69%) and associated with osteitis in 40 (62.5%) patients. Infection was grade 3 in 70.3% cases. Thirty-nine patients had received antibiotics before hospital admission. Among the 71 samples, 62 (87.32%) cultures were positive: 53 (85.48%) monomicrobial and 9 (14.52%) bimicrobial. Aerobic Gram-positive cocci (76%) were the most frequent from ulcerations: Staphylococcus aureus (32.39%), Streptococcus sp (18.30%). Negative coagulase staphylococci have been found in 23.94% cases. Aerobic gram-negative bacilli have been isolated from 24% ulcerations. No factor was associated with the type of bacteria. Gram-positive pathogen cocci showed a high sensitivity to amoxicillin-clavulanic acid and oxacillin. No methicillin-resistant Staphylococcus aureus (MRSA) or extended-spectrum beta lactamase Enterobacteriaceae (ESBL) have been isolated. A better design is necessary to a clarification of bacterial flora in diabetic foot infections. Prevention of bacterial resistance is also needed.

  18. Increase in Antibiotic-Resistant Gram-Negative Bacterial Infections in Febrile Neutropenic Children

    OpenAIRE

    Lee, Joon Hee; Kim, Seul-Ki; Kim, Seong Koo; Han, Seung Beom; Lee, Jae Wook; Lee, Dong-Gun; Chung, Nack-Gyun; Cho, Bin; Jeong, Dae Chul; Kang, Jin Han; Kim, Hack-Ki

    2016-01-01

    Background The incidence of bacteremia caused by Gram-negative bacteria has increased recently in febrile neutropenic patients with the increase of antibiotic-resistant Gram-negative bacterial infections. This study aimed to identify the distribution of causative bacteria and the proportion of antibiotic-resistant bacteria in bacteremia diagnosed in febrile neutropenic children. Materials and Methods The medical records of febrile neutropenic children diagnosed with bacteremia between 2010 an...

  19. In vitro Evaluation of the Effct of Bacterial Extract, Isolated From Infected Hydatid Cysts, on Protoscolex

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    Sardari M

    2017-03-01

    Full Text Available Introduction: To date, surgery has been the treatment of choice for hydatid cyst, with regard to danger of leakage of hydatid cyst contents into viscera and production of secondary cysts, aftr spread of protoscolices. Diffrent scolicidal agents get injected into cyst for preventing the secondary cyst production, which may cause diffrent side effcts in host, especially in the surrounding tissues. In this research, the scolicidal effcts of bacterial extract isolated from infected hydatid cyst was evaluated. Methods: In this experimental-laboratorial study, at fist, isolation and identifiation of the infecting bacteria of hydatid cyst were performed at the level of species. Thn, total the bacterial extract was prepared by sonication method, and serial dilutions 1.1, 1.2, 1.4, 1.8, 1.16, 1.32 and 1.64( were prepared using sterile saline as the solvent. Th obtained alive larvae at the times of 5, 10, 20, 40 and 60 minutes were placed in those dilutions and mean of dead protoscoleces were determined using eosin exclusive staining method. Results: Th identifid bacteria isolated from the infected hydatid cysts were as follows: E. coli, Staphylococcus aureus, S. saprophyticus, Proteus mirabilis and Pseudomonas aeruginosa. Th extract of isolated bacteria at the mentioned times had no considerable scolicidal effcts. For example, the whole extract of P. aeruginosa aftr 60 minutes of exposure showed a maximum of 13.17%. scolicidal effct. Conclusion: Th results of this study showed low scolicidal effct of bacterial extracts isolated from hydatid cyst. Degeneration of scolices in infected cysts can be due to other reasons than bacterial extract.

  20. [Use of transport medium in sputum bacterial culture examination of lower airway infection].

    Science.gov (United States)

    Muraki, Masato; Kitaguchi, Sayako; Ichihashi, Hideo; Tsuji, Fumio; Ohmori, Takashi; Haraguchi, Ryuta; Tohda, Yuji

    2006-06-01

    Our medical institution does not have a bacterial culture facility, requiring outsourcing of bacterial culture tests. Due to the time elapsed from the time of specimen collection to culturing, the identification of causative bacteria in respiratory tract infections tends to be difficult. We therefore used transport medium for sputum bacteria examinations. Expectorated purulent or purulent-mucous sputum specimens were collected from 32 patients with lower respiratory tract infection. We divided each of the sputum specimens into the two treatment groups: transport medium (Seedswab gamma2) ndar and stad disinfection container. Paired samples prepared from each patient were sent out for bacterial culture together. The time elapsed from collection to delivery to the lab were as follows: day 0 (same day, n = 14 patients), day 1 (n = 15), day 2 (n = 2), and day 3 (n = 1). The identified causative bacteria were Streptococcus pneumoniae (n = 6 patients), Haemophilus influenzae (n =5), Pseudomonas aeruginosa (n = 4), Staphylococcus aureus (n = 2), Moraxella catarrhalis (n = 2), Klebsiella pneumoniae (n = 1), and Streptococcus agalactiae (n = 1). Samples prepared by each of the two methods gave similar results. The utility of transport medium for examination of general bacteria for lower airway infection from sputum samples was not demonstrated. The rate of detection of bacteria decreased, when the transport of samples was delayed. Therefore, we need to send the sputum specimens as quickly as possible.

  1. Regulatory T cell suppressive potency dictates the balance between bacterial proliferation and clearance during persistent Salmonella infection.

    Directory of Open Access Journals (Sweden)

    Tanner M Johanns

    Full Text Available The pathogenesis of persistent infection is dictated by the balance between opposing immune activation and suppression signals. Herein, virulent Salmonella was used to explore the role and potential importance of Foxp3-expressing regulatory T cells in dictating the natural progression of persistent bacterial infection. Two distinct phases of persistent Salmonella infection are identified. In the first 3-4 weeks after infection, progressively increasing bacterial burden was associated with delayed effector T cell activation. Reciprocally, at later time points after infection, reductions in bacterial burden were associated with robust effector T cell activation. Using Foxp3(GFP reporter mice for ex vivo isolation of regulatory T cells, we demonstrate that the dichotomy in infection tempo between early and late time points is directly paralleled by drastic changes in Foxp3(+ Treg suppressive potency. In complementary experiments using Foxp3(DTR mice, the significance of these shifts in Treg suppressive potency on infection outcome was verified by enumerating the relative impacts of regulatory T cell ablation on bacterial burden and effector T cell activation at early and late time points during persistent Salmonella infection. Moreover, Treg expression of CTLA-4 directly paralleled changes in suppressive potency, and the relative effects of Treg ablation could be largely recapitulated by CTLA-4 in vivo blockade. Together, these results demonstrate that dynamic regulation of Treg suppressive potency dictates the course of persistent bacterial infection.

  2. The bacterial effector HopX1 targets JAZ transcriptional repressors to activate jasmonate signaling and promote infection in Arabidopsis.

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    Selena Gimenez-Ibanez

    2014-02-01

    Full Text Available Pathogenicity of Pseudomonas syringae is dependent on a type III secretion system, which secretes a suite of virulence effector proteins into the host cytoplasm, and the production of a number of toxins such as coronatine (COR, which is a mimic of the plant hormone jasmonate-isoleuce (JA-Ile. Inside the plant cell, effectors target host molecules to subvert the host cell physiology and disrupt defenses. However, despite the fact that elucidating effector action is essential to understanding bacterial pathogenesis, the molecular function and host targets of the vast majority of effectors remain largely unknown. Here, we found that effector HopX1 from Pseudomonas syringae pv. tabaci (Pta 11528, a strain that does not produce COR, interacts with and promotes the degradation of JAZ proteins, a key family of JA-repressors. We show that hopX1 encodes a cysteine protease, activity that is required for degradation of JAZs by HopX1. HopX1 associates with JAZ proteins through its central ZIM domain and degradation occurs in a COI1-independent manner. Moreover, ectopic expression of HopX1 in Arabidopsis induces the expression of JA-dependent genes, represses salicylic acid (SA-induced markers, and complements the growth of a COR-deficient P. syringae pv. tomato (Pto DC3000 strain during natural bacterial infections. Furthermore, HopX1 promoted susceptibility when delivered by the natural type III secretion system, to a similar extent as the addition of COR, and this effect was dependent on its catalytic activity. Altogether, our results indicate that JAZ proteins are direct targets of bacterial effectors to promote activation of JA-induced defenses and susceptibility in Arabidopsis. HopX1 illustrates a paradigm of an alternative evolutionary solution to COR with similar physiological outcome.

  3. Gut microbiota dysbiosis is associated with inflammation and bacterial translocation in mice with CCl4-induced fibrosis.

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    Isabel Gómez-Hurtado

    Full Text Available BACKGROUND: Gut is the major source of endogenous bacteria causing infections in advanced cirrhosis. Intestinal barrier dysfunction has been described in cirrhosis and account for an increased bacterial translocation rate. HYPOTHESIS AND AIMS: We hypothesize that microbiota composition may be affected and change along with the induction of experimental cirrhosis, affecting the inflammatory response. ANIMALS AND METHODS: Progressive liver damage was induced in Balb/c mice by weight-controlled oral administration of carbon tetrachloride. Laparotomies were performed at weeks 6, 10, 13 and 16 in a subgroup of treated mice (n = 6/week and control animals (n = 4/week. Liver tissue specimens, mesenteric lymph nodes, intestinal content and blood were collected at laparotomies. Fibrosis grade, pro-fibrogenic genes expression, gut bacterial composition, bacterial translocation, host's specific butyrate-receptor GPR-43 and serum cytokine levels were measured. RESULTS: Expression of pro-fibrogenic markers was significantly increased compared with control animals and correlated with the accumulated dose of carbon tetrachloride. Bacterial translocation episodes were less frequent in control mice than in treated animals. Gram-positive anaerobic Clostridia spp count was decreased in treated mice compared with control animals and with other gut common bacterial species, altering the aerobic/anaerobic ratio. This fact was associated with a decreased gene expression of GPR43 in neutrophils of treated mice and inversely correlated with TNF-alpha and IL-6 up-regulation in serum of treated mice along the study protocol. This pro-inflammatory scenario favoured blood bacterial translocation in treated animals, showing the highest bacterial translocation rate and aerobic/anaerobic ratio at the same weeks. CONCLUSIONS: Gut microbiota alterations are associated with the development of an inflammatory environment, fibrosis progression and bacterial translocation in

  4. Development of fatal intestinal inflammation in MyD88 deficient mice co-infected with helminth and bacterial enteropathogens.

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    Libo Su

    2014-07-01

    Full Text Available Infections with intestinal helminth and bacterial pathogens, such as enteropathogenic Escherichia coli, continue to be a major global health threat for children. To determine whether and how an intestinal helminth parasite, Heligomosomoides polygyrus, might impact the TLR signaling pathway during the response to a bacterial enteropathogen, MyD88 knockout and wild-type C57BL/6 mice were infected with H. polygyrus, the bacterial enteropathogen Citrobacter rodentium, or both. We found that MyD88 knockout mice co-infected with H. polygyrus and C. rodentium developed more severe intestinal inflammation and elevated mortality compared to the wild-type mice. The enhanced susceptibility to C. rodentium, intestinal injury and mortality of the co-infected MyD88 knockout mice were found to be associated with markedly reduced intestinal phagocyte recruitment, decreased expression of the chemoattractant KC, and a significant increase in bacterial translocation. Moreover, the increase in bacterial infection and disease severity were found to be correlated with a significant downregulation of antimicrobial peptide expression in the intestinal tissue in co-infected MyD88 knockout mice. Our results suggest that the MyD88 signaling pathway plays a critical role for host defense and survival during helminth and enteric bacterial co-infection.

  5. Legionella pneumophila infection of Drosophila S2 cells induces only minor changes in mitochondrial dynamics.

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    Elizabeth Wen Sun

    Full Text Available During infection of cells by Legionella pneumophila, the bacterium secretes a large number of effector proteins into the host cell cytoplasm, allowing it to alter many cellular processes and make the vacuole and the host cell into more hospitable environments for bacterial replication. One major change induced by infection is the recruitment of ER-derived vesicles to the surface of the vacuole, where they fuse with the vacuole membrane and prevent it from becoming an acidified, degradative compartment. However, the recruitment of mitochondria to the region of the vacuole has also been suggested by ultrastructural studies. In order to test this idea in a controlled and quantitative experimental system, and to lay the groundwork for a genome-wide screen for factors involved in mitochondrial recruitment, we examined the behavior of mitochondria during the early stages of Legionella pneumophila infection of Drosophila S2 cells. We found that the density of mitochondria near vacuoles formed by infection with wild type Legionella was not different from that found in dotA(- mutant-infected cells during the first 4 hours after infection. We then examined 4 parameters of mitochondrial motility in infected cells: velocity of movement, duty cycle of movement, directional persistence and net direction. In the 4 hours following infection, most of these measures were indistinguishable between wild type and dotA(-.infection. However, wild type Legionella did induce a modest shift in the velocity distribution toward faster movement compared dotA(- infection, and a small downward shift in the duty cycle distribution. In addition, wild type infection produced mitochondrial movement that was biased in the direction of the bacterial vacuole relative to dotA-, although not enough to cause a significant accumulation within 10 um of the vacuole. We conclude that in this host cell, mitochondria are not strongly recruited to the vacuole, nor is their motility

  6. Identification of in vivo-induced genes during infection of chickens with Salmonella enterica serovar Enteritidis.

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    Geng, Shizhong; Liu, Zhicheng; Lin, Zhijie; Barrow, Paul; Pan, Zhiming; Li, Qiuchun; Jiao, Xinan

    2015-06-01

    Chickens are an important source of food worldwide and are often infected with food-poisoning serovars of Salmonella enterica, frequently Salmonella Enteritidis (SE), without exhibiting clinical signs of disease. Ivi (in vivo induced) genes identified using in vivo-induced antigen technology (IVIAT) are expressed only during bacterial infection and have the potential value of identifying epidemic strains and antigens which can form the basis for sub-unit vaccine development. We applied IVIAT to SE strain 50041 and identified 42 ivi genes. Eight representative ivi genes were further confirmed by qRT-PCR as being expressed only in vivo within 48 h of infection compared with that of in vitro-cultured. Although our results indicated that the identified ivi genes are expressed only in vivo, further research is needed to elucidate the exact roles of these genes during infection and pathogenesis.

  7. MHC class I expression dependent on bacterial infection and parental factors in whitefish embryos (Salmonidae).

    Science.gov (United States)

    Clark, Emily S; Wilkins, Laetitia G E; Wedekind, Claus

    2013-10-01

    Ecological conditions can influence not only the expression of a phenotype, but also the heritability of a trait. As such, heritable variation for a trait needs to be studied across environments. We have investigated how pathogen challenge affects the expression of MHC genes in embryos of the lake whitefish Coregonus palaea. In order to experimentally separate paternal (i.e. genetic) from maternal and environmental effects, and determine whether and how stress affects the heritable variation for MHC expression, embryos were produced in full-factorial in vitro fertilizations, reared singly, and exposed at 208 degree days (late-eyed stage) to either one of two strains of Pseudomonas fluorescens that differ in their virulence characteristics (one increased mortality, while both delayed hatching time). Gene expression was assessed 48 h postinoculation, and virulence effects of the bacterial infection were monitored until hatching. We found no evidence of MHC class II expression at this stage of development. MHC class I expression was markedly down-regulated in reaction to both pseudomonads. While MHC expression could not be linked to embryo survival, the less the gene was expressed, the earlier the embryos hatched within each treatment group, possibly due to trade-offs between immune function and developmental rate or further factors that affect both hatching timing and MHC expression. We found significant additive genetic variance for MHC class I expression in some treatments. That is, changes in pathogen pressures could induce rapid evolution in MHC class I expression. However, we found no additive genetic variance in reaction norms in our study population.

  8. (68) Ga-labeled Ciprofloxacin Conjugates as Radiotracers for Targeting Bacterial Infection.

    Science.gov (United States)

    Satpati, Drishty; Arjun, Chanda; Krishnamohan, Repaka; Samuel, Grace; Banerjee, Sharmila

    2016-05-01

    With an aim of developing a bacteria-specific molecular imaging agent, ciprofloxacin has been modified with a propylamine spacer and linked to two common bifunctional chelators, p-SCN-Bz-DOTA and p-SCN-Bz-NOTA. The two ciprofloxacin conjugates, CP-PA-SCN-Bz-DOTA (1) and CP-PA-SCN-Bz-NOTA (2), were radiolabeled with (68)Ga in >90% radiochemical yield and were moderately stable in vitro for 4 h. The efficacy of (68)Ga-1 and (68)Ga-2 has been investigated in vitro in Staphylococcus aureus cells where bacterial binding of the radiotracers (0.9-1.0% for (68)Ga-1 and 1.6-2.3% for (68)Ga-2) could not be blocked in the presence of excess amount of unlabeled ciprofloxacin. However, uptake of radiotracers in live bacterial cells was significantly higher (p 68)Ga-1 and (68)Ga-2 was tested in vivo in rats where the infected muscle-to-inflamed muscle ((68)Ga-1: 2 ± 0.2, (68)Ga-2: 3 ± 0.5) and infected muscle-to-normal muscle ratios ((68)Ga-1: 3 ± 0.4, (68)Ga-2: 6.6 ± 0.8) were found to improve at 120 min p.i. Fast blood clearance and renal excretion was observed for both the radiotracers. The two (68)Ga-labeled infection targeting radiotracers could discriminate between bacterial infection and inflammation in vivo and are worthy of further detailed investigation as infection imaging agents at the clinical level.

  9. Metabolic Requirements of Escherichia coli in Intracellular Bacterial Communities during Urinary Tract Infection Pathogenesis

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    Matt S. Conover

    2016-04-01

    Full Text Available Uropathogenic Escherichia coli (UPEC is the primary etiological agent of over 85% of community-acquired urinary tract infections (UTIs. Mouse models of infection have shown that UPEC can invade bladder epithelial cells in a type 1 pilus-dependent mechanism, avoid a TLR4-mediated exocytic process, and escape into the host cell cytoplasm. The internalized UPEC can clonally replicate into biofilm-like intracellular bacterial communities (IBCs of thousands of bacteria while avoiding many host clearance mechanisms. Importantly, IBCs have been documented in urine from women and children suffering acute UTI. To understand this protected bacterial niche, we elucidated the transcriptional profile of bacteria within IBCs using microarrays. We delineated the upregulation within the IBC of genes involved in iron acquisition, metabolism, and transport. Interestingly, lacZ was highly upregulated, suggesting that bacteria were sensing and/or utilizing a galactoside for metabolism in the IBC. A ΔlacZ strain displayed significantly smaller IBCs than the wild-type strain and was attenuated during competitive infection with a wild-type strain. Similarly, a galK mutant resulted in smaller IBCs and attenuated infection. Further, analysis of the highly upregulated gene yeaR revealed that this gene contributes to oxidative stress resistance and type 1 pilus production. These results suggest that bacteria within the IBC are under oxidative stress and, consistent with previous reports, utilize nonglucose carbon metabolites. Better understanding of the bacterial mechanisms used for IBC development and establishment of infection may give insights into development of novel anti-virulence strategies.

  10. The red flour beetle as a model for bacterial oral infections.

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    Barbara Milutinović

    Full Text Available Experimental infection systems are important for studying antagonistic interactions and coevolution between hosts and their pathogens. The red flour beetle Tribolium castaneum and the spore-forming bacterial insect pathogen Bacillus thuringiensis (Bt are widely used and tractable model organisms. However, they have not been employed yet as an efficient experimental system to study host-pathogen interactions. We used a high throughput oral infection protocol to infect T. castaneum insects with coleopteran specific B. thuringiensis bv. tenebrionis (Btt bacteria. We found that larval mortality depends on the dietary spore concentration and on the duration of exposure to the spores. Furthermore, differential susceptibility of larvae from different T. castaneum populations indicates that the host genetic background influences infection success. The recovery of high numbers of infectious spores from the cadavers indicates successful replication of bacteria in the host and suggests that Btt could establish infectious cycles in T. castaneum in nature. We were able to transfer plasmids from Btt to a non-pathogenic but genetically well-characterised Bt strain, which was thereafter able to successfully infect T. castaneum, suggesting that factors residing on the plasmids are important for the virulence of Btt. The availability of a genetically accessible strain will provide an ideal model for more in-depth analyses of pathogenicity factors during oral infections. Combined with the availability of the full genome sequence of T. castaneum, this system will enable analyses of host responses during infection, as well as addressing basic questions concerning host-parasite coevolution.

  11. Foreign Body Infection Models to Study Host-Pathogen Response and Antimicrobial Tolerance of Bacterial Biofilm

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    Justyna Nowakowska

    2014-08-01

    Full Text Available The number of implanted medical devices is steadily increasing and has become an effective intervention improving life quality, but still carries the risk of infection. These infections are mainly caused by biofilm-forming staphylococci that are difficult to treat due to the decreased susceptibility to both antibiotics and host defense mechanisms. To understand the particular pathogenesis and treatment tolerance of implant-associated infection (IAI animal models that closely resemble human disease are needed. Applications of the tissue cage and catheter abscess foreign body infection models in the mouse will be discussed herein. Both models allow the investigation of biofilm and virulence of various bacterial species and a comprehensive insight into the host response at the same time. They have also been proven to serve as very suitable tools to study the anti-adhesive and anti-infective efficacy of different biomaterial coatings. The tissue cage model can additionally be used to determine pharmacokinetics, efficacy and cytotoxicity of antimicrobial compounds as the tissue cage fluid can be aspirated repeatedly without the need to sacrifice the animal. Moreover, with the advance in innovative imaging systems in rodents, these models may offer new diagnostic measures of infection. In summary, animal foreign body infection models are important tools in the development of new antimicrobials against IAI and can help to elucidate the complex interactions between bacteria, the host immune system, and prosthetic materials.

  12. In vitro and in vivo evaluation of [{sup 18}F]ciprofloxacin for the imaging of bacterial infections with PET

    Energy Technology Data Exchange (ETDEWEB)

    Langer, Oliver; Brunner, Martin; Zeitlinger, Markus; Mueller, Ulrich; Lackner, Edith; Joukhadar, Christian; Mueller, Markus [Medical University Vienna, Division of Clinical Pharmacokinetics, Department of Clinical Pharmacology, Vienna (Austria); Ziegler, Sophie; Minar, Erich [Medical University Vienna, Division of Angiology, Department of Internal Medicine II, Vienna (Austria); Dobrozemsky, Georg [Medical University Vienna, Department of Nuclear Medicine, Vienna (Austria); Medical University Vienna, Department of Biomedical Engineering and Physics, Vienna (Austria); Mitterhauser, Markus; Wadsak, Wolfgang; Dudczak, Robert; Kletter, Kurt [Medical University Vienna, Department of Nuclear Medicine, Vienna (Austria)

    2005-02-01

    The suitability of the{sup 18}F-labelled fluoroquinolone antibiotic ciprofloxacin ([{sup 18}F]ciprofloxacin) for imaging of bacterial infections with positron emission tomography (PET) was assessed in vitro and in vivo. For the in vitro experiments, suspensions of various E. colistrains were incubated with different concentrations of [{sup 18}F]ciprofloxacin (0.01-5.0 {mu}g/ml) and radioactivity retention was measured in a gamma counter. For the in vivo experiments, 725 {+-} 9 MBq [{sup 18}F]ciprofloxacin was injected intravenously into four patients with microbiologically proven bacterial soft tissue infections of the lower extremities and time-radioactivity curves were recorded in infected and uninfected tissue for 5 h after tracer injection. Binding of [{sup 18}F]ciprofloxacin to bacterial cells was rapid, non-saturable and readily reversible. Moreover, bacterial binding of the agent was similar in ciprofloxacin-resistant and ciprofloxacin-susceptible clinical isolates. These findings suggest that non-specific binding rather than specific binding to bacterial type II topoisomerase enzymes is the predominant mechanism of bacterial retention of the radiotracer. PET studies in the four patients with microbiologically proven bacterial soft tissue infections demonstrated locally increased radioactivity uptake in infected tissue, with peak ratios between infected and uninfected tissue ranging from 1.8 to 5.5. Radioactivity was not retained in infected tissue and appeared to wash out with a similar elimination half-life as in uninfected tissue, suggesting that the kinetics of [{sup 18}F]ciprofloxacin in infected tissue are governed by increased blood flow and vascular permeability due to local infection rather than by a binding process. Taken together, our results indicate that [{sup 18}F]ciprofloxacin is not suited as a bacteria-specific infection imaging agent for PET. (orig.)

  13. Clinical prediction model to aid emergency doctors managing febrile children at risk of serious bacterial infections: Diagnostic study

    NARCIS (Netherlands)

    R.G. Nijman (Ruud); Y. Vergouwe (Yvonne); M.J. Thompson (Matthew); M.V. Veen (Mirjam Van); A.H.J. van Meurs (Alfred); J. van der Lei (Johan); E.W. Steyerberg (Ewout); H.A. Moll (Henriëtte); R. Oostenbrink (Rianne)

    2013-01-01

    textabstractObjective: To derive, cross validate, and externally validate a clinical prediction model that assesses the risks of different serious bacterial infections in children with fever at the emergency department. Design: Prospective observational diagnostic study. Setting: Three paediatric em

  14. TIR Domain-Containing Adapter-Inducing Beta Interferon (TRIF) Mediates Immunological Memory against Bacterial Pathogens.

    Science.gov (United States)

    Kanagavelu, Saravana; Flores, Claudia; Termini, J M; Romero, Laura; Riveron, Reldy; Ruiz, Jose; Arditi, Moshe; Schesser, Kurt; Fukata, Masayuki

    2015-11-01

    Induction of adaptive immunity leads to the establishment of immunological memory; however, how innate immunity regulates memory T cell function remains obscure. Here we show a previously undefined mechanism in which innate and adaptive immunity are linked by TIR domain-containing adapter-inducing beta interferon (TRIF) during establishment and reactivation of memory T cells against Gram-negative enteropathogens. Absence of TRIF in macrophages (Mϕs) but not dendritic cells led to a predominant generation of CD4(+) central memory T cells that express IL-17 during enteric bacterial infection in mice. TRIF-dependent type I interferon (IFN) signaling in T cells was essential to Th1 lineage differentiation and reactivation of memory T cells. TRIF activated memory T cells to facilitate local neutrophil influx and enhance bacterial elimination. These results highlight the importance of TRIF as a mediator of the innate and adaptive immune interactions in achieving the protective properties of memory immunity against Gram-negative bacteria and suggest TRIF as a potential therapeutic target.

  15. Animals devoid of pulmonary system as infection models in the study of lung bacterial pathogens.

    Science.gov (United States)

    López Hernández, Yamilé; Yero, Daniel; Pinos-Rodríguez, Juan M; Gibert, Isidre

    2015-01-01

    Biological disease models can be difficult and costly to develop and use on a routine basis. Particularly, in vivo lung infection models performed to study lung pathologies use to be laborious, demand a great time and commonly are associated with ethical issues. When infections in experimental animals are used, they need to be refined, defined, and validated for their intended purpose. Therefore, alternative and easy to handle models of experimental infections are still needed to test the virulence of bacterial lung pathogens. Because non-mammalian models have less ethical and cost constraints as a subjects for experimentation, in some cases would be appropriated to include these models as valuable tools to explore host-pathogen interactions. Numerous scientific data have been argued to the more extensive use of several kinds of alternative models, such as, the vertebrate zebrafish (Danio rerio), and non-vertebrate insects and nematodes (e.g., Caenorhabditis elegans) in the study of diverse infectious agents that affect humans. Here, we review the use of these vertebrate and non-vertebrate models in the study of bacterial agents, which are considered the principal causes of lung injury. Curiously none of these animals have a respiratory system as in air-breathing vertebrates, where respiration takes place in lungs. Despite this fact, with the present review we sought to provide elements in favor of the use of these alternative animal models of infection to reveal the molecular signatures of host-pathogen interactions.

  16. UGT-29 protein expression and localization during bacterial infection in Caenorhabditis elegans

    Science.gov (United States)

    Wong, Rui-Rui; Lee, Song-Hua; Nathan, Sheila

    2014-09-01

    The nematode Caenorhabditis elegans is routinely used as an animal model to delineate complex molecular mechanisms involved in the host response to pathogen infection. Following up on an earlier study on host-pathogen interaction, we constructed a ugt-29::GFP transcriptional fusion transgenic worm strain to examine UGT-29 protein expression and localization upon bacterial infection. UGT-29 orthologs can be found in higher organisms including humans and is proposed as a member of the UDP-Glucoronosyl Transferase family of proteins which are involved in phase II detoxification of compounds detrimental to the host organism. Under uninfected conditions, UGT-29::GFP fusion protein was highly expressed in the C. elegans anterior pharynx and intestine, two major organs involved in detoxification. We further evaluated the localization of the enzyme in worms infected with the bacterial pathogen, Burkholderia pseudomallei. The infected ugt-29::GFP transgenic strain exhibited increased fluorescence in the pharynx and intestine with pronounced fluorescence also extending to body wall muscle. This transcriptional fusion GFP transgenic worm is a convenient and direct tool to provide information on UGT detoxification enzyme gene expression and could be a useful tool for a number of diverse applications.

  17. Animals devoid of pulmonary system as infection models in the study of lung bacterial pathogens

    Directory of Open Access Journals (Sweden)

    Yamilé eLópez Hernández

    2015-02-01

    Full Text Available Biological disease models can be difficult and costly to develop and use on a routine basis. Particularly, in vivo lung infection models performed to study lung pathologies use to be laborious, demand a great time and commonly are associated with ethical issues. When infections in experimental animals are used, they need to be refined, defined, and validated for their intended purpose. Therefore, alternative and easy to handle models of experimental infections are still needed to test the virulence of bacterial lung pathogens. Because non-mammalian models have less ethical and cost constraints as a subjects for experimentation, in some cases would be appropriated to include these models as a valuate tools to explore host-pathogen interactions. Numerous scientific data have been argued to the more extensive use of several kinds of alternative models, such as, the vertebrate zebrafish (Danio rerio, and non-vertebrate insects and nematodes (e.g. Caenorhabditis elegans in the study of diverse infectious agents that affect humans. Here we review the use of these vertebrate and non-vertebrate models in the study of bacterial agents, which are considered the principal causes of lung injury. Curiously none of these animals have a respiratory system as in air-breathing vertebrates, where respiration takes place in lungs. Despite this fact, with the present review we sought to provide elements in favour of the use of these alternative animal models of infection to reveal the molecular signatures of host-pathogen interactions.

  18. Comparative tissue transcriptomics reveal prompt inter-organ communication in response to local bacterial kidney infection

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    Rhen Mikael

    2011-02-01

    Full Text Available Abstract Background Mucosal infections elicit inflammatory responses via regulated signaling pathways. Infection outcome depends strongly on early events occurring immediately when bacteria start interacting with cells in the mucosal membrane. Hitherto reported transcription profiles on host-pathogen interactions are strongly biased towards in vitro studies. To detail the local in vivo genetic response to infection, we here profiled host gene expression in a recent experimental model that assures high spatial and temporal control of uropathogenic Escherichia coli (UPEC infection within the kidney of a live rat. Results Transcriptional profiling of tissue biopsies from UPEC-infected kidney tissue revealed 59 differentially expressed genes 8 h post-infection. Their relevance for the infection process was supported by a Gene Ontology (GO analysis. Early differential expression at 3 h and 5 h post-infection was of low statistical significance, which correlated to the low degree of infection. Comparative transcriptomics analysis of the 8 h data set and online available studies of early local infection and inflammation defined a core of 80 genes constituting a "General tissue response to early local bacterial infections". Among these, 25% were annotated as interferon-γ (IFN-γ regulated. Subsequent experimental analyses confirmed a systemic increase of IFN-γ in rats with an ongoing local kidney infection, correlating to splenic, rather than renal Ifng induction and suggested this inter-organ communication to be mediated by interleukin (IL-23. The use of comparative transcriptomics allowed expansion of the statistical data handling, whereby relevant data could also be extracted from the 5 h data set. Out of the 31 differentially expressed core genes, some represented specific 5 h responses, illustrating the value of comparative transcriptomics when studying the dynamic nature of gene regulation in response to infections. Conclusion Our hypothesis

  19. Fungal and Bacterial Infection Mitigation with Antibiotic and Antifungal Loaded Biopolymer Sponges

    Science.gov (United States)

    Parker, Ashley Cox

    Musculoskeletal injuries are some of the most prevalent injuries in both civilian and military populations and their infections can be difficult to treat, often resulting in multiple surgeries and increased costs. In both previous and recent military operations, extremity injuries have been the most common battlefield injuries and many involve complex, open fractures. These extremity injuries are especially susceptible to multiple pathogenic, and sometimes drug resistant, bacteria and fungi. Fungal infections have recently become increasingly problematic in both military and civilian populations and have significantly higher amputation rates than those from bacterial infections. Many of these bacterial and fungal strains adhere to tissue and implanted orthopaedic hardware within wounds, forming biofilms. These problematic, often polymicrobial, infections threaten the health of the patient, but the risk also exists of spreading within hospitals to become prominent resistant infections. Local antimicrobial delivery releases high levels of antimicrobials directly to injured wound tissue, overcoming sub-bactericidal or subfungicidal antimicrobial levels present in the avascular wound zones. This research will determine the ability of modified chitosan sponges, buffered with sodium acetate or blended with polyethylene glycol (PEG), to act as short term adjunctive therapies to initial surgical treatment for delivering both antibiotics and/or antifungals for early abatement of infection. The objective of this work was to evaluate both types of modified sponges for in vitro and in vivo material characteristics and device functionality. In vitro analysis demonstrated both the buffered and PEG modified chitosan sponges exhibited increased degradation and functional cytocompatibility. The chitosan/PEG sponges were able to be loaded with hydrophobic antifungals and the sponges released in vitro biologically active concentrations, alone or in combination with the antibiotic

  20. Synthesis and biodistribution of {sup 99m}Tc-Vancomycin in a model of bacterial infection

    Energy Technology Data Exchange (ETDEWEB)

    Roohi, S.; Mushtaq, A. [Isotope Production Div., Pakistan Inst. of Nuclear Science and Technology, Islamabad (Pakistan); Malik, S.A. [Dept. of Biological Sciences, Quaid-e-Azam Univ., Islamabad (Pakistan)

    2005-07-01

    Vancomycin Hydrochloride is an antibiotic produced by the growth of certain strains of Streptomyces orientalis. As vancomycin hydrochloride is poorly absorbed after oral administration; it is given intravenously for therapy of systemic infections. Vancomycin was labeled with technetium-99m pertechnetate using SnCl{sub 2} . 2H{sub 2}O as reducing agent. The labeling efficiency depends on ligand/reductant ratio, pH, and volume of reaction mixture. Radiochemical purity and stability of {sup 99m}Tc-Vancomycin was determined by thin layer chromatography. Biodistribution studies of {sup 99m}Tc-Vancomycin were performed in a model of bacterial infection in Sprague-Dawley rats. A significantly higher accumulation of {sup 99m}Tc-Vancomycin was seen at sites of S. aureus infected animals. Whereas uptake of {sup 99m}Tc-Vancomycin in turpentine inflamed rats were quite low. (orig.)

  1. Osteomyelitis in a Paleozoic reptile: ancient evidence for bacterial infection and its evolutionary significance

    Science.gov (United States)

    Reisz, Robert R.; Scott, Diane M.; Pynn, Bruce R.; Modesto, Sean P.

    2011-06-01

    We report on dental and mandibular pathology in Labidosaurus hamatus, a 275 million-year-old terrestrial reptile from North America and associate it with bacterial infection in an organism that is characterized by reduced tooth replacement. Analysis of the surface and internal mandibular structure using mechanical and CT-scanning techniques permits the reconstruction of events that led to the pathology and the possible death of the individual. The infection probably occurred as a result of prolonged exposure of the dental pulp cavity to oral bacteria, and this exposure was caused by injury to the tooth in an animal that is characterized by reduced tooth replacement cycles. In these early reptiles, the reduction in tooth replacement is an evolutionary innovation associated with strong implantation and increased oral processing. The dental abscess observed in L. hamatus, the oldest known infection in a terrestrial vertebrate, provides clear evidence of the ancient association between terrestrial vertebrates and their oral bacteria.

  2. Yeast cell wall extract induces disease resistance against bacterial and fungal pathogens in Arabidopsis thaliana and Brassica crop.

    Directory of Open Access Journals (Sweden)

    Mari Narusaka

    Full Text Available Housaku Monogatari (HM is a plant activator prepared from a yeast cell wall extract. We examined the efficacy of HM application and observed that HM treatment increased the resistance of Arabidopsis thaliana and Brassica rapa leaves to bacterial and fungal infections. HM reduced the severity of bacterial leaf spot and anthracnose on A. thaliana and Brassica crop leaves with protective effects. In addition, gene expression analysis of A. thaliana plants after treatment with HM indicated increased expression of several plant defense-related genes. HM treatment appears to induce early activation of jasmonate/ethylene and late activation of salicylic acid (SA pathways. Analysis using signaling mutants revealed that HM required SA accumulation and SA signaling to facilitate resistance to the bacterial pathogen Pseudomonas syringae pv. maculicola and the fungal pathogen Colletotrichum higginsianum. In addition, HM-induced resistance conferred chitin-independent disease resistance to bacterial pathogens in A. thaliana. These results suggest that HM contains multiple microbe-associated molecular patterns that activate defense responses in plants. These findings suggest that the application of HM is a useful tool that may facilitate new disease control methods.

  3. Clinical features of bacterial vaginosis in a murine model of vaginal infection with Gardnerella vaginalis.

    Directory of Open Access Journals (Sweden)

    Nicole M Gilbert

    Full Text Available Bacterial vaginosis (BV is a dysbiosis of the vaginal flora characterized by a shift from a Lactobacillus-dominant environment to a polymicrobial mixture including Actinobacteria and gram-negative bacilli. BV is a common vaginal condition in women and is associated with increased risk of sexually transmitted infection and adverse pregnancy outcomes such as preterm birth. Gardnerella vaginalis is one of the most frequently isolated bacterial species in BV. However, there has been much debate in the literature concerning the contribution of G. vaginalis to the etiology of BV, since it is also present in a significant proportion of healthy women. Here we present a new murine vaginal infection model with a clinical isolate of G. vaginalis. Our data demonstrate that this model displays key features used clinically to diagnose BV, including the presence of sialidase activity and exfoliated epithelial cells with adherent bacteria (reminiscent of clue cells. G. vaginalis was capable of ascending uterine infection, which correlated with the degree of vaginal infection and level of vaginal sialidase activity. The host response to G. vaginalis infection was characterized by robust vaginal epithelial cell exfoliation in the absence of histological inflammation. Our analyses of clinical specimens from women with BV revealed a measureable epithelial exfoliation response compared to women with normal flora, a phenotype that, to our knowledge, is measured here for the first time. The results of this study demonstrate that G. vaginalis is sufficient to cause BV phenotypes and suggest that this organism may contribute to BV etiology and associated complications. This is the first time vaginal infection by a BV associated bacterium in an animal has been shown to parallel the human disease with regard to clinical diagnostic features. Future studies with this model should facilitate investigation of important questions regarding BV etiology, pathogenesis and

  4. Synthesis and biodistribution of a novel (⁹⁹m)TcN complex of norfloxacin dithiocarbamate as a potential agent for bacterial infection imaging.

    Science.gov (United States)

    Zhang, Shijian; Zhang, Weifang; Wang, Yue; Jin, Zhonghui; Wang, Xuebin; Zhang, Junbo; Zhang, Yanyan

    2011-03-16

    Achieving a (⁹⁹m)Tc-labeled fluoroquinolone derivative as a single photon emission computed tomography (SPECT) tracer is considered to be of great interest. The norfloxacin dithiocarbamate (NFXDTC) was synthesized and radiolabeled with a [(⁹⁹m)TcN]²(+) intermediate to form the (⁹⁹m)TcN-NFXDTC complex in high yield. The radiochemical purity of (⁹⁹m)TcN-NFXDTC was over 90%, as measured by thin layer chromatography (TLC) and high performance liquid chromatography (HPLC), without any notable decomposition at room temperature over a period of 6 h. The partition coefficient and electrophoresis results indicated that (⁹⁹m)TcN-NFXDTC was lipophilic and neutral. The bacterial binding assay studies showed tht (⁹⁹m)TcN-NFXDTC had a good binding affinity. Biodistribution results in bacterial infected mice showed that (⁹⁹m)TcN-NFXDTC had a higher uptake at the sites of infection and better abscess/blood and abscess/muscle ratios than those of (⁹⁹m)Tc-ciprofloxacin and (⁹⁹m)TcN-CPFXDTC (CPFXDTC = ciprofloxacin dithiocarbamate). The biodistribution results of (⁹⁹m)TcN-NFXDTC in bacterially infected mice and in mice with turpentine-induced abscesses indicated that (⁹⁹m)TcN-NFXDTC was suited to be a bacteria-specific infection imaging agent. Single photon emission computed tomography (SPECT) image studies showed there was a visible accumulation in infection sites, suggesting that it would be a promising candidate for bacterial infection imaging.

  5. Phage Therapy in Bacterial Infections Treatment: One Hundred Years After the Discovery of Bacteriophages.

    Science.gov (United States)

    Cisek, Agata Anna; Dąbrowska, Iwona; Gregorczyk, Karolina Paulina; Wyżewski, Zbigniew

    2017-02-01

    The therapeutic use of bacteriophages has seen a renewal of interest blossom in the last few years. This reversion is due to increased difficulties in the treatment of antibiotic-resistant strains of bacteria. Bacterial resistance to antibiotics, a serious problem in contemporary medicine, does not implicate resistance to phage lysis mechanisms. Lytic bacteriophages are able to kill antibiotic-resistant bacteria at the end of the phage infection cycle. Thus, the development of phage therapy is potentially a way to improve the treatment of bacterial infections. However, there are antibacterial phage therapy difficulties specified by broadening the knowledge of the phage nature and influence on the host. It has been shown during experiments that both innate and adaptive immunity are involved in the clearance of phages from the body. Immunological reactions against phages are related to the route of administration and may vary depending on the type of bacterial viruses. For that reason, it is very important to test the immunological response of every single phage, particularly if intravenous therapy is being considered. The lack of these data in previous years was one of the reasons for phage therapy abandonment despite its century-long study. Promising results of recent research led us to look forward to a phage therapy that can be applied on a larger scale and subsequently put it into practice.

  6. Clinical evaluation of technetium-99m infecton for the localisation of bacterial infection

    Energy Technology Data Exchange (ETDEWEB)

    Britton, K.E. [Department of Nuclear Medicine, St. Bartholomew`s Hospital, London (United Kingdom); Vinjamuri, S. [Department of Nuclear Medicine, St. Bartholomew`s Hospital, London (United Kingdom); Hall, A.V. [Medical Microbiology, St. Bartholomew`s Hospital, London (United Kingdom); Solanki, K. [Department of Nuclear Medicine, St. Bartholomew`s Hospital, London (United Kingdom); Siraj, Q.H. [Department of Nuclear Medicine, St. Bartholomew`s Hospital, London (United Kingdom); Bomanji, J. [Department of Nuclear Medicine, St. Bartholomew`s Hospital, London (United Kingdom); Das, S. [Medical Microbiology, St. Bartholomew`s Hospital, London (United Kingdom)

    1997-05-01

    The aim of the study was to distinguish infection from inflammation in patients with suspected infection using technetium-99m Infecton. Ninety-nine patients (102 studies) referred for infection evaluation underwent imaging with 400 MBq {sup 99m}Tc-Infecton at 1 and 4 h. Most patients had appropriate microbiological tests and about half (56) had radiolabelled white cell scans as well. No adverse effects were noted in any patient. The clinical efficacy of {sup 99m}Tc-Infecton depended in part on whether imaging was undertaken during antibiotic therapy for infection or not. In consultation with the microbiologist, 5-14 days of appropriate and successful antibiotic therapy was considered adequate to classify some results as true-negatives. The figures for sensitivity and specificity of {sup 99m}Tc-Infecton for active or unsuccessfully treated infection were 83% and 91% respectively. It is concluded that {sup 99m}Tc-Infecton imaging contributed to the differential diagnosis of inflammation. It is being used as the first imaging modality when bacterial infection is suspected. (orig.). With 2 figs., 1 tab.

  7. Morphological description of bacterial infection of digestive glands in the terrestrial isopod porcellio scaber (Isopoda, crustacea)

    Science.gov (United States)

    Drobne; Strus; Znidarsic; Zidar

    1999-01-01

    Morphological studies of the hepatopancreas of the terrestrial isopod Porcellio scaber revealed bacterial infection. The percentage of infected animals collected from the same site varied from 0 to 10% during the 4 years of study. Transmission electron microscopy, scanning electron microscopy, and light microscopy revealed that infected glands differed from those in healthy isopods. The most prominent sign was white spots between 100 and 200 &mgr;m in diameter along the entire gland. These spots were aggregations of vacuoles in the cells that were densely filled with bacteria in different phases of the developmental cycle that included the formation of small, dense, rod-shaped infective bacteria and much larger spherical multiplying cells filled with aggregates of polysomes and a chromatin network. Occasionally, large sphericles were filled with homogeneous electron-dense material. Bacteria were not observed in the cell nucleus. Small vacuoles of less than 5 &mgr;m were filled predominately with spherical bacteria but rod-shaped forms were also present in large numbers. Larger vacuoles of 10 to 20 &mgr;m in the main were densely filled with rod-shaped bacteria. According to the literature on the morphological characteristics of bacteria infecting invertebrates, those described in our study would be classified in the genus Rickettsiella. However, most recent investigations show that besides morphological investigations, genetic ones are also needed to define the taxonomic position of bacteria that infect invertebrates. Copyright 1999 Academic Press.

  8. Anti-Inflammatory Effects of Vitamin D on Human Immune Cells in the Context of Bacterial Infection

    Science.gov (United States)

    Hoe, Edwin; Nathanielsz, Jordan; Toh, Zheng Quan; Spry, Leena; Marimla, Rachel; Balloch, Anne; Mulholland, Kim; Licciardi, Paul V.

    2016-01-01

    Vitamin D induces a diverse range of biological effects, including important functions in bone health, calcium homeostasis and, more recently, on immune function. The role of vitamin D during infection is of particular interest given data from epidemiological studies suggesting that vitamin D deficiency is associated with an increased risk of infection. Vitamin D has diverse immunomodulatory functions, although its role during bacterial infection remains unclear. In this study, we examined the effects of 1,25(OH)2D3, the active metabolite of vitamin D, on peripheral blood mononuclear cells (PBMCs) and purified immune cell subsets isolated from healthy adults following stimulation with the bacterial ligands heat-killed pneumococcal serotype 19F (HK19F) and lipopolysaccharide (LPS). We found that 1,25(OH)2D3 significantly reduced pro-inflammatory cytokines TNF-α, IFN-γ, and IL-1β as well as the chemokine IL-8 for both ligands (three- to 53-fold), while anti-inflammatory IL-10 was increased (two-fold, p = 0.016) in HK19F-stimulated monocytes. Levels of HK19F-specific IFN-γ were significantly higher (11.7-fold, p = 0.038) in vitamin D-insufficient adults (50 nmol/L). Vitamin D also shifted the pro-inflammatory/anti-inflammatory balance towards an anti-inflammatory phenotype and increased the CD14 expression on monocytes (p = 0.008) in response to LPS but not HK19F stimulation. These results suggest that 1,25(OH)2D3 may be an important regulator of the inflammatory response and supports further in vivo and clinical studies to confirm the potential benefits of vitamin D in this context. PMID:27973447

  9. Metformin prevents the effects of Pseudomonas aeruginosa on airway epithelial tight junctions and restricts hyperglycaemia-induced bacterial growth.

    Science.gov (United States)

    Patkee, Wishwanath R A; Carr, Georgina; Baker, Emma H; Baines, Deborah L; Garnett, James P

    2016-04-01

    Lung disease and elevation of blood glucose are associated with increased glucose concentration in the airway surface liquid (ASL). Raised ASL glucose is associated with increased susceptibility to infection by respiratory pathogens including Staphylococcus aureus and Pseudomonas aeruginosa. We have previously shown that the anti-diabetes drug, metformin, reduces glucose-induced S. aureus growth across in vitro airway epithelial cultures. The aim of this study was to investigate whether metformin has the potential to reduce glucose-induced P. aeruginosa infections across airway epithelial (Calu-3) cultures by limiting glucose permeability. We also explored the effect of P. aeruginosa and metformin on airway epithelial barrier function by investigating changes in tight junction protein abundance. Apical P. aeruginosa growth increased with basolateral glucose concentration, reduced transepithelial electrical resistance (TEER) and increased paracellular glucose flux. Metformin pre-treatment of the epithelium inhibited the glucose-induced growth of P. aeruginosa, increased TEER and decreased glucose flux. Similar effects on bacterial growth and TEER were observed with the AMP activated protein kinase agonist, 5-aminoimidazole-4-carboxamide ribonucleotide. Interestingly, metformin was able to prevent the P. aeruginosa-induced reduction in the abundance of tight junction proteins, claudin-1 and occludin. Our study highlights the potential of metformin to reduce hyperglycaemia-induced P. aeruginosa growth through airway epithelial tight junction modulation, and that claudin-1 and occludin could be important targets to regulate glucose permeability across airway epithelia and supress bacterial growth. Further investigation into the mechanisms regulating metformin and P. aeruginosa action on airway epithelial tight junctions could yield new therapeutic targets to prevent/suppress hyperglycaemia-induced respiratory infections, avoiding the use of antibiotics.

  10. Adrenergic blockade does not abolish elevated glucose turnover during bacterial infection

    Energy Technology Data Exchange (ETDEWEB)

    Hargrove, D.M.; Bagby, G.J.; Lang, C.H.; Spitzer, J.J. (Louisiana State Univ., New Orleans (USA))

    1988-01-01

    Infusions of adrenergic antagonists were used to investigate the role of catecholamines in infection-induced elevations of glucose kinetics. Infection was produced in conscious catheterized rats by repeated subcutaneous injections of live Escherichia coli over 24 h. Glucose kinetics were measured by the constant intravenous infusion of (6-{sup 3}H)- and (U-{sup 14}C)glucose. Compared with noninfected rats, infected animals were hyperthermic and showed increased rates of glucose appearance, clearance, and recycling as well as mild hyperlacticacidemia. Plasma catecholamine concentrations were increased by 50-70% in the infected rats, but there were no differences in plasma glucagon, corticosterone, and insulin levels. Adrenergic blockade was produced by primed constant infusion of both propranolol ({beta}-blocker) and phentolamine ({alpha}-blocker). A 2-h administration of adrenergic antagonists did not attenuate the elevated glucose kinetics or plasma lactate concentration in the infected rats, although it abolished the hyperthermia. In a second experiment, animals were infused with propranolol and phentolamine beginning 1 h before the first injection of E. coli and throughout the course of infection. Continuous adrenergic blockade failed to attenuate infection-induced elevations in glucose kinetics and plasma lactate. These results indicate that the adrenergic system does not mediate the elevated glucose metabolism observed in this mild model of infection.

  11. Analysis of Campylobacter jejuni infection in the gnotobiotic piglet and genome-wide identification of bacterial factors required for infection

    Science.gov (United States)

    de Vries, Stefan P. W.; Linn, Aileen; Macleod, Kareen; MacCallum, Amanda; Hardy, Simon P.; Douce, Gill; Watson, Eleanor; Dagleish, Mark P.; Thompson, Hal; Stevenson, Andy; Kennedy, David; Baig, Abiyad; Coward, Chris; Maskell, Duncan J.; Smith, David G. E.; Grant, Andrew J.; Everest, Paul

    2017-01-01

    To investigate how Campylobacter jejuni causes the clinical symptoms of diarrhoeal disease in humans, use of a relevant animal model is essential. Such a model should mimic the human disease closely in terms of host physiology, incubation period before onset of disease, clinical signs and a comparable outcome of disease. In this study, we used a gnotobiotic piglet model to study determinants of pathogenicity of C. jejuni. In this model, C. jejuni successfully established infection and piglets developed an increased temperature with watery diarrhoea, which was caused by a leaky epithelium and reduced bile re-absorption in the intestines. Further, we assessed the C. jejuni genes required for infection of the porcine gastrointestinal tract utilising a transposon (Tn) mutant library screen. A total of 123 genes of which Tn mutants showed attenuated piglet infection were identified. Our screen highlighted a crucial role for motility and chemotaxis, as well as central metabolism. In addition, Tn mutants of 14 genes displayed enhanced piglet infection. This study gives a unique insight into the mechanisms of C. jejuni disease in terms of host physiology and contributing bacterial factors. PMID:28281647

  12. Relationship between bacterial infection and evaluation using a laser fluorescence device, DIAGNOdent.

    Science.gov (United States)

    Iwami, Yukiteru; Shimizu, Ayako; Narimatsu, Masahiro; Hayashi, Mikako; Takeshige, Fumio; Ebisu, Shigeyuki

    2004-10-01

    The aim of this in vitro study was to investigate the relationship between bacterial infections in carious dentin when detected by two different methods -- polymerase chain reaction (PCR), and a laser fluorescence device, DIAGNOdent. Dentin was removed every 300 micro m in the direction of the pulp chamber in 10 extracted molars with occlusal dentin caries and 3 extracted sound molars. Dentin surfaces were evaluated using DIAGNOdent, and dentinal tissue samples were removed by using a round bur before and after each removal. Bacterial DNA in the dentinal tissues was detected by PCR, using primers based on the nucleotide sequence of a conserved region of the 16S rDNA, and yielded a PCR product of 466 bp. The rates of bacterial detection increased as the DIAGNOdent values increased. In the 10 specimens, the lowest DIAGNOdent value at which bacteria were detected was 15.6; at DIAGNOdent values below 15.6, no bacteria were detected. The results of a receiver operating characteristic (ROC) curve for the DIAGNOdent values showed that the area under the ROC curve was 0.91. This study clarified the relationship between the DIAGNOdent values of dentin caries and the rates of bacterial detection.

  13. Elucidating Sources and Roles of Granzymes A and B during Bacterial Infection and Sepsis

    Directory of Open Access Journals (Sweden)

    Maykel A. Arias

    2014-07-01

    Full Text Available During bacterial sepsis, proinflammatory cytokines contribute to multiorgan failure and death in a process regulated in part by cytolytic cell granzymes. When challenged with a sublethal dose of the identified mouse pathogen Brucella microti, wild-type (WT and granzyme A (gzmA−/− mice eliminate the organism from liver and spleen in 2 or 3 weeks, whereas the bacteria persist in mice lacking perforin or granzyme B as well as in mice depleted of Tc cells. In comparison, after a fatal challenge, only gzmA−/− mice exhibit increased survival, which correlated with reduced proinflammatory cytokines. Depletion of natural killer (NK cells protects WT mice from sepsis without influencing bacterial clearance and the transfer of WT, but not gzmA−/− NK, cells into gzmA−/− recipients restores the susceptibility to sepsis. Therefore, infection-related pathology, but not bacterial clearance, appears to require gzmA, suggesting the protease may be a therapeutic target for the prevention of bacterial sepsis without affecting immune control of the pathogen.

  14. The use of C-reactive protein in predicting bacterial co-Infection in children with bronchiolitis

    Directory of Open Access Journals (Sweden)

    Mohamad Fares

    2011-03-01

    Full Text Available Background: Bronchiolitis is a potentially life-threatening respiratory illness commonly affecting children who are less than two years of age. Patients with viral lower respiratory tract infection are at risk for co-bacterial infection. Aim: The aim of our study was to evaluate the use of C-reactive protein (CRP in predicting bacterial co-infection in patients hospitalized for bronchiolitis and to correlate the results with the use of antibiotics. Patients and Methods: This is a prospective study that included patients diagnosed with bronchiolitis admitted to Makassed General Hospital in Beirut from October 2008 to April 2009. A tracheal aspirate culture was taken from all patients with bronchiolitis on admission to the hospital. Blood was drawn to test C-reactive protein level, white cell count, transaminases level, and blood sugar level. Results: Forty-nine patients were enrolled in the study and were divided into two groups. Group 1 included patients with positive tracheal aspirate culture and Group 2 included those with negative culture. All patients with a CRP level ≥2 mg/dL have had bacterial co-infection. White cell count, transaminases and blood sugar levels were not predictive for bacterial co-infection. The presence of bacterial co-infection increased the length of hospital stay in the first group by 2 days compared to those in the second group. Conclusion: Bacterial co-infection is frequent in infants with moderate to severe bronchiolitis and requires admission. Our data showed that a CRP level greater than 1.1 mg/dL raised suspicion for bacterial co-infection. Thus, a tracheal aspirate should be investigated microbiologically in all hospitalized patients in order to avoid unnecessary antimicrobial therapy and to shorten the duration of the hospital stay.

  15. Septic Shock Induced by Bacterial Prostatitis with Morganella morganii subsp. morganii in a Posttransplantation Patient

    Directory of Open Access Journals (Sweden)

    Xiaofan Li

    2015-01-01

    Full Text Available Bacterial infection is a common complication after Hematopoietic Stem Cell Transplantation (HSCT. Morganella morganii is ubiquitous Gram-negative facultative anaerobe, which may cause many kinds of opportunistic infection. Herein we report a case of a 55-year-old man who presented with frequent urination, urgency, and mild pain that comes and goes low in the abdomen and around the anus. The patient had a medical history of chronic prostatitis for 4 years. He received HLA-matched sibling allo-HSCT because of angioimmunoblastic T-cell lymphoma 29 months ago. The routine examination of prostatic fluid showed increased leukocytes and the culture of prostatic fluid showed Morganella morganii subsp. morganii. The patient developed chills and fever 18 hours after examination. Both urine culture and blood culture showed Morganella morganii subsp. morganii. The patient was successfully treated with antibiotic therapy and septic shock management. Taken together, Morganella morganii should be considered a possible pathogen when immunocompromised patients develop prostatitis. Also, prostatic massage could be a possible trigger of septic shock induced by Morganella morganii subsp. morganii in a posttransplantation patient.

  16. Septic Shock Induced by Bacterial Prostatitis with Morganella morganii subsp. morganii in a Posttransplantation Patient

    Science.gov (United States)

    Li, Xiaofan; Chen, Jianhui

    2015-01-01

    Bacterial infection is a common complication after Hematopoietic Stem Cell Transplantation (HSCT). Morganella morganii is ubiquitous Gram-negative facultative anaerobe, which may cause many kinds of opportunistic infection. Herein we report a case of a 55-year-old man who presented with frequent urination, urgency, and mild pain that comes and goes low in the abdomen and around the anus. The patient had a medical history of chronic prostatitis for 4 years. He received HLA-matched sibling allo-HSCT because of angioimmunoblastic T-cell lymphoma 29 months ago. The routine examination of prostatic fluid showed increased leukocytes and the culture of prostatic fluid showed Morganella morganii subsp. morganii. The patient developed chills and fever 18 hours after examination. Both urine culture and blood culture showed Morganella morganii subsp. morganii. The patient was successfully treated with antibiotic therapy and septic shock management. Taken together, Morganella morganii should be considered a possible pathogen when immunocompromised patients develop prostatitis. Also, prostatic massage could be a possible trigger of septic shock induced by Morganella morganii subsp. morganii in a posttransplantation patient. PMID:26798544

  17. Septic Shock Induced by Bacterial Prostatitis with Morganella morganii subsp. morganii in a Posttransplantation Patient.

    Science.gov (United States)

    Li, Xiaofan; Chen, Jianhui

    2015-01-01

    Bacterial infection is a common complication after Hematopoietic Stem Cell Transplantation (HSCT). Morganella morganii is ubiquitous Gram-negative facultative anaerobe, which may cause many kinds of opportunistic infection. Herein we report a case of a 55-year-old man who presented with frequent urination, urgency, and mild pain that comes and goes low in the abdomen and around the anus. The patient had a medical history of chronic prostatitis for 4 years. He received HLA-matched sibling allo-HSCT because of angioimmunoblastic T-cell lymphoma 29 months ago. The routine examination of prostatic fluid showed increased leukocytes and the culture of prostatic fluid showed Morganella morganii subsp. morganii. The patient developed chills and fever 18 hours after examination. Both urine culture and blood culture showed Morganella morganii subsp. morganii. The patient was successfully treated with antibiotic therapy and septic shock management. Taken together, Morganella morganii should be considered a possible pathogen when immunocompromised patients develop prostatitis. Also, prostatic massage could be a possible trigger of septic shock induced by Morganella morganii subsp. morganii in a posttransplantation patient.

  18. Dietary fatty acids and immune response to food-borne bacterial infections.

    Science.gov (United States)

    Harrison, Lisa M; Balan, Kannan V; Babu, Uma S

    2013-05-22

    Functional innate and acquired immune responses are required to protect the host from pathogenic bacterial infections. Modulation of host immune functions may have beneficial or deleterious effects on disease outcome. Different types of dietary fatty acids have been shown to have variable effects on bacterial clearance and disease outcome through suppression or activation of immune responses. Therefore, we have chosen to review research across experimental models and food sources on the effects of commonly consumed fatty acids on the most common food-borne pathogens, including Salmonella sp., Campylobacter sp., Shiga toxin-producing Escherichia coli, Shigella sp., Listeria monocytogenes, and Staphylococcus aureus. Altogether, the compilation of literature suggests that no single fatty acid is an answer for protection from all food-borne pathogens, and further research is necessary to determine the best approach to improve disease outcomes.

  19. [Autochthonous acute viral and bacterial infections of the central nervous system (meningitis and encephalitis)].

    Science.gov (United States)

    Pérez-Ruiz, Mercedes; Vicente, Diego; Navarro-Marí, José María

    2008-07-01

    Rapid diagnosis of acute viral and bacterial infections of the central nervous system (meningitis and encephalitis) is highly important for the clinical management of the patient and helps to establish early therapy that may solve life-threatening situations, to avoid unnecessary empirical treatments, to reduce hospital stay, and to facilitate appropriate interventions in the context of public health. Molecular techniques, especially real-time polymerase chain reaction, have become the fastest and most sensitive diagnostic procedures for autochthonous viral meningitis and encephalitis, and their role is becoming increasingly important for the diagnosis and control of most frequent acute bacterial meningitides. Automatic and closed systems may encourage the widespread and systematic use of molecular techniques for the diagnosis of these neurological syndromes in most laboratories.

  20. Detection of Fastidious Vaginal Bacteria in Women with HIV Infection and Bacterial Vaginosis

    Directory of Open Access Journals (Sweden)

    Caroline Mitchell

    2009-01-01

    Full Text Available Background. Fastidious bacteria have been associated with bacterial vaginosis (BV using PCR methods. We assessed the prevalence of these bacteria in HIV-1 infected women and their relationship with vaginal pH and shedding of HIV-1 RNA. Methods. 64 cervicovaginal lavage (CVL samples were collected from 51 women. Vaginal microbiota were characterized using 8 bacterium-specific quantitative PCR assays. Results. Women with the fastidious bacteria Bacterial Vaginosis Associated Bacterium (BVAB 1, 2, and 3 showed a trend to increased HIV-1 shedding (OR 2.59–3.07, P=.14–.17. Absence of Lactobacillus crispatus (P<.005 and presence of BVAB2 (P<.001 were associated with elevated vaginal pH. BVAB1, 2, and 3 were highly specific indicators of BV in HIV-infected women, with specificities of 89%–93%. Conclusions. Fastidious bacteria (BVAB 1, 2, and 3 remain specific indicators of BV in HIV-infected women, and BVAB2 may contribute to the elevated vaginal pH that is a hallmark of this syndrome.

  1. mTORC1-Activated Monocytes Increase Tregs and Inhibit the Immune Response to Bacterial Infections

    Science.gov (United States)

    Tu, Huaijun; Guo, Wei; Wang, Shixuan; Xue, Ting; Yang, Fei; Zhang, Xiaoyan; Yang, Yazhi; Wan, Qian; Shi, Zhexin; Zhan, Xulong

    2016-01-01

    The TSC1/2 heterodimer, a key upstream regulator of the mTOR, can inhibit the activation of mTOR, which plays a critical role in immune responses after bacterial infections. Monocytes are an innate immune cell type that have been shown to be involved in bacteremia. However, how the mTOR pathway is involved in the regulation of monocytes is largely unknown. In our study, TSC1 KO mice and WT mice were infected with E. coli. When compared to WT mice, we found higher mortality, greater numbers of bacteria, decreased expression of coactivators in monocytes, increased numbers of Tregs, and decreased numbers of effector T cells in TSC1 KO mice. Monocytes obtained from TSC1 KO mice produced more ROS, IL-6, IL-10, and TGF-β and less IL-1, IFN-γ, and TNF-α. Taken together, our results suggest that the inhibited immune functioning in TSC1 KO mice is influenced by mTORC1 activation in monocytes. The reduced expression of coactivators resulted in inhibited effector T cell proliferation. mTORC1-activated monocytes are harmful during bacterial infections. Therefore, inhibiting mTORC1 signaling through rapamycin administration could rescue the harmful aspects of an overactive immune response, and this knowledge provides a new direction for clinical therapy.

  2. Profile of oritavancin and its potential in the treatment of acute bacterial skin structure infections

    Science.gov (United States)

    Mitra, Subhashis; Saeed, Usman; Havlichek, Daniel H; Stein, Gary E

    2015-01-01

    Oritavancin, a semisynthetic derivative of the glycopeptide antibiotic chloroeremomycin, received the US Food and Drug Administration approval for the treatment of acute bacterial skin and skin structure infections caused by susceptible Gram-positive bacteria in adults in August 2014. This novel second-generation semisynthetic lipoglycopeptide antibiotic has activity against a broad spectrum of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate S. aureus (VISA), and vancomycin-resistant Enterococcus. Oritavancin inhibits bacterial cell wall synthesis and is rapidly bactericidal against many Gram-positive pathogens. The long half-life of this drug enables a single-dose administration. Oritavancin is not metabolized in the body, and the unchanged drug is slowly excreted by the kidneys. In two large Phase III randomized, double-blind, clinical trials, oritavancin was found to be non-inferior to vancomycin in achieving the primary composite end point in the treatment of acute Gram-positive skin and skin structure infections. Adverse effects noted were mostly mild with nausea, headache, and vomiting being the most common reported side effects. Oritavancin has emerged as another useful antimicrobial agent for treatment of acute Gram-positive skin and skin structure infections, including those caused by MRSA and VISA. PMID:26185459

  3. Profile of oritavancin and its potential in the treatment of acute bacterial skin structure infections

    Directory of Open Access Journals (Sweden)

    Mitra S

    2015-07-01

    Full Text Available Subhashis Mitra, Usman Saeed, Daniel H Havlichek, Gary E Stein Department of Infectious Diseases, Michigan State University, East Lansing, MI, USA Abstract: Oritavancin, a semisynthetic derivative of the glycopeptide antibiotic chloroeremomycin, received the US Food and Drug Administration approval for the treatment of acute bacterial skin and skin structure infections caused by susceptible Gram-positive bacteria in adults in August 2014. This novel second-generation semisynthetic lipoglycopeptide antibiotic has activity against a broad spectrum of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA, vancomycin-intermediate S. aureus (VISA, and vancomycin-resistant Enterococcus. Oritavancin inhibits bacterial cell wall synthesis and is rapidly bactericidal against many Gram-positive pathogens. The long half-life of this drug enables a single-dose administration. Oritavancin is not metabolized in the body, and the unchanged drug is slowly excreted by the kidneys. In two large Phase III randomized, double-blind, clinical trials, oritavancin was found to be non-inferior to vancomycin in achieving the primary composite end point in the treatment of acute Gram-positive skin and skin structure infections. Adverse effects noted were mostly mild with nausea, headache, and vomiting being the most common reported side effects. Oritavancin has emerged as another useful antimicrobial agent for treatment of acute Gram-positive skin and skin structure infections, including those caused by MRSA and VISA. Keywords: antibiotic, Gram-positive bacteria, MRSA, VRSA, vancomycin, MIC

  4. Identification of Francisella novicida mutants that fail to induce prostaglandin E2 synthesis by infected macrophages.

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    Matthew Dale Woolard

    2013-02-01

    Full Text Available Francisella tularensis is the causative agent of tularemia. We have previously shown that infection with F. tularensis Live Vaccine Strain (LVS induces macrophages to synthesize prostaglandin E2 (PGE2. Synthesis of PGE2 by F. tularensis infected macrophages results in decreased T cell proliferation in vitro and increased bacterial survival in vivo. Although we understand some of the biological consequences of F. tularensis induced PGE2 synthesis by macrophages, we do not understand the cellular pathways (neither host nor bacterial that result in up-regulation of the PGE2 biosynthetic pathway in F. tularensis infected macrophages. We took a genetic approach to begin to understand the molecular mechanisms of bacterial induction of PGE2 synthesis from infected macrophages. To identify F. tularensis genes necessary for the induction of PGE2 in primary macrophages, we infected cells with individual mutants from the closely related strain Francisella tularensis subspecies novicida U112 (U112 two allele mutant library. Twenty genes were identified that when disrupted resulted in U112 mutant strains unable to induce the synthesis of PGE2 by infected macrophages. Fourteen of the genes identified are located within the Francisella pathogenicity island (FPI. Genes in the FPI are required for F. tularensis to escape from the phagosome and replicate in the cytosol, which might account for the failure of U112 with transposon insertions within the FPI to induce PGE2. This implies that U112 mutant strains that do not grow intracellularly would also not induce PGE2. We found that U112 clpB::Tn grows within macrophages yet fails to induce PGE2, while U112 pdpA::Tn does not grow yet does induce PGE2. We also found that U112 iglC::Tn neither grows nor induces PGE2. These findings indicate that there is dissociation between intracellular growth and the ability of F. tularensis to induce PGE2 synthesis. These mutants provide a critical entrée into the pathways used

  5. Antagonistic effect of toll-like receptor signaling and bacterial infections on transplantation tolerance*

    OpenAIRE

    Alegre, Maria-Luisa; Chen, Luqiu; Wang, Tongmin; Ahmed, Emily; Wang, Chyung-Ru; Chong, Anita

    2009-01-01

    The induction of donor-specific tolerance remains a major goal in the field of transplantation immunology. Therapies that target costimulatory molecules can induce tolerance to heart and pancreatic islet allografts in mouse models, but fail to do so following transplantation of skin or intestinal allografts. We have proposed that organs colonized by commensal bacteria such as skin, lung and intestine may be resistant to such therapies as a result of bacterial translocation at the time of tran...

  6. Increased interleukin-18 in the gingival tissues evokes chronic periodontitis after bacterial infection.

    Science.gov (United States)

    Yoshinaka, Kotaro; Shoji, Noriaki; Nishioka, Takashi; Sugawara, Yumiko; Hoshino, Tomoaki; Sugawara, Shunji; Sasano, Takashi

    2014-01-01

    Periodontal disease is a chronic inflammatory disease that results in the breakdown of the tooth-supporting tissues, and can ultimately lead to resorption of the alveolar bone. Recently, several studies have shown a close relationship between increased interleukin-18 (IL-18) levels and the pathogenesis of chronic periodontitis, a major cause of tooth loss. However, it has yet to be shown whether chronic periodontitis results from or causes an increase in IL-18 after bacterial infection. In the present study, we investigated how IL-18 overexpression relates to periodontal disease using IL-18 transgenic (Tg) mice. IL-18Tg and wild-type mice were inoculated intraorally with Porphyromonas (P.) gingivalis, which has been implicated in the etiology of chronic periodontitis. Seventy days after P. gingivalis infection, alveolar bone loss and gingival cytokine levels were assessed using histo-morphological analysis and enzyme-linked immuno-absorbent assay, respectively. Periodontal bone loss was evoked in IL-18Tg mice, but not in wild-type mice. Interestingly, levels of bone-resorptive cytokines, including IL-1α, IL-1β, tumor necrosis factor-α, and IL-6, were unchanged in the gingival tissues of IL-18Tg mice infected with P. gingivalis, although levels of interferon γ (a proinflammatory T-helper 1 cytokine) decreased. RT-PCR analysis showed elevated expression of mRNAs for receptor activator of nuclear factor kappa-B ligand (a key stimulator of osteoclast development and activation) and CD40 ligand (a marker of T cell activation) in the gingiva of IL-18Tg mice infected with P. gingivalis. We conclude that increased IL-18 in the gingival tissues evokes chronic periodontitis after bacterial infection, presumably via a T cell-mediated pathway.

  7. Interleukin-35 is upregulated in response to influenza virus infection and secondary bacterial pneumonia.

    Science.gov (United States)

    Chen, Yi; Wang, Chuan-jiang; Lin, Shi-hui; Zhang, Mu; Li, Sheng-yuan; Xu, Fang

    2016-05-01

    Postinfluenza pneumococcal pneumonia is an important cause of global morbidity and mortality. What causes this increased susceptibility is not well elucidated. IL-35 is a newly described cytokine in infectious tolerance. A murine model was established to study postinfluenza pneumococcal pneumonia and evaluate the role of IL-35 in host defense against postinfluenza pneumococcal pneumonia. Pulmonary IL-35 was rapidly up-regulated during murine influenza infection, which was partially mediated by type I IFN-α/β receptor signaling pathway. Secondary pneumococcal infection led to a synergistic IL-35 response in influenza-infected mice. Clinical analysis showed that IL-35 levels were significantly elevated in the patients with influenza infection compared with healthy individuals and influenza infection could induce IL-35 production from human peripheral blood mononuclear cells. These data suggest that IL-35 contributes to the increased susceptibility to secondary pneumococcal pneumonia at least in part by inhibiting the early immune response.

  8. Bacterial lipopolysaccharide inhibits influenza virus infection of human macrophages and the consequent induction of CD8+ T cell immunity

    NARCIS (Netherlands)

    Short, K.R.; Vissers, M.; Kleijn, S. de; Zomer, A.L.; Kedzierska, K.; Grant, E.; Reading, P.C.; Hermans, P.W.M.; Ferwerda, G.; Diavatopoulos, D.A.

    2014-01-01

    It is well established that infection with influenza A virus (IAV) facilitates secondary bacterial disease. However, there is a growing body of evidence that the microbial context in which IAV infection occurs can affect both innate and adaptive responses to the virus. To date, these studies have be

  9. Serum interleukin-6 in the diagnosis of bacterial infection in cirrhotic patients

    Science.gov (United States)

    Wu, Yinlian; Wang, Mingfang; Zhu, Yueyong; Lin, Su

    2016-01-01

    Abstract Background: The diagnostic accuracy of interleukin-6 (IL-6) in predicting bacterial infection in cirrhotic patients remains unclear. The aim of this meta-analysis is to explore the potential diagnostic value of IL-6 in cirrhotic patients. Methods: We systematically searched PubMed, Embase (via OvidSP), Web of Science, the Cochrane Library, and Scopus for studies published from inception to October 2015. Studies were enrolled if they included assessment of the accuracy of IL-6 in the diagnosis of bacterial infection in cirrhotic patients and provided sufficient data to construct a 2 × 2 contingency table. Results: Totally, 535 studies were searched in the initial database and finally 6 studies involving 741 patients were included for the final analysis. The pooled sensitivity, specificity and diagnostic odds ratio were 0.85 (95% confidence interval [CI], 0.64–0.94), 0.91 (95% CI, 0.80–0.96) and 52.89 (95% CI, 15.21–183.86), respectively. The pooled positive likelihood ratio was 8.99 (95% CI, 4.13–19.55) and the pooled negative likelihood ratio was 0.17 (95% CI, 0.07–0.43). The area under the receiver operating characteristic curve was 0.94 (95% CI, 0.92–0.96). Conclusion: This meta-analysis suggests IL-6 has a high diagnostic value for the differentiation of bacterial infection in patients with cirrhosis. PMID:27741137

  10. Elevation of serum thymidine kinase 1 in a bacterial infection: canine pyometra.

    Science.gov (United States)

    Sharif, H; Hagman, R; Wang, L; Eriksson, S

    2013-01-01

    Pyometra is a bacterial infection of the uterus that is common in dogs and is potentially life-threatening if delayed in diagnosis and/or treatment. Thymidine kinase 1 (TK1) is a cytosolic enzyme involved in DNA precursor synthesis, and it is also present in serum from patients with malignant diseases. TK1 has been used as a cell proliferation biomarker for many years in human medicine and recently in dogs. However, little is known regarding serum TK1 levels in individuals with bacterial infection. The objective of this study was to determine the activity of serum TK1 in dogs with pyometra and compare it with hematologic and biochemical parameters, e.g., acute phase proteins and inflammatory mediators such as C-reactive protein and Prostaglandin F(2α). Serum and plasma TK1 activity of 40 healthy female dogs and 54 dogs with pyometra were analyzed using an optimized [(3)H]-thymidine phosphorylation assay. TK1 activities in serum or plasma were significantly higher in dogs with pyometra as compared with healthy female dogs (mean ± SD: 4.0 ± 7.3 pmol/min/mL in the pyometra group and 1.07 ± 0.34 pmol/min/mL in healthy control group). However, there was no difference in TK1 activity between systemic inflammatory response syndrome (SIRS) positive (n = 38) and SIRS negative (n = 16) pyometra cases. Furthermore, the plasma TK1 activity decreased in six and increased in one pyometra patients (n = 10), 24 h after ovariohysterectomy. No significant correlations (P > 0.05) were found between TK1 activity and hematological or other biochemical parameters. In conclusion, the TK1 activity was significantly elevated in dogs with pyometra. Further studies are needed to evaluate the mechanism and role of serum TK1 activity in bacterial infections and its possible diagnostic or prognostic value.

  11. Viral-bacterial interactions and risk of acute otitis media complicating upper respiratory tract infection.

    Science.gov (United States)

    Pettigrew, Melinda M; Gent, Janneane F; Pyles, Richard B; Miller, Aaron L; Nokso-Koivisto, Johanna; Chonmaitree, Tasnee

    2011-11-01

    Acute otitis media (AOM) is a common complication of upper respiratory tract infection whose pathogenesis involves both viruses and bacteria. We examined risks of acute otitis media associated with specific combinations of respiratory viruses and acute otitis media bacterial pathogens. Data were from a prospective study of children ages 6 to 36 months and included viral and bacterial culture and quantitative PCR for respiratory syncytial virus (RSV), human bocavirus, and human metapneumovirus. Repeated-measure logistic regression was used to assess the relationship between specific viruses, bacteria, and the risk of acute otitis media complicating upper respiratory tract infection. In unadjusted analyses of data from 194 children, adenovirus, bocavirus, Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis were significantly associated with AOM (P virus loads (≥3.16 × 10(7) copies/ml) experienced increased acute otitis media risk. Higher viral loads of bocavirus and metapneumovirus were not significantly associated with acute otitis media. In adjusted models controlling for the presence of key viruses, bacteria, and acute otitis media risk factors, acute otitis media risk was independently associated with high RSV viral load with Streptococcus pneumoniae (odds ratio [OR], 4.40; 95% confidence interval [CI], 1.90 and 10.19) and Haemophilus influenzae (OR, 2.04; 95% CI, 1.38 and 3.02). The risk was higher for the presence of bocavirus and H. influenzae together (OR, 3.61; 95% CI, 1.90 and 6.86). Acute otitis media risk differs by the specific viruses and bacteria involved. Acute otitis media prevention efforts should consider methods for reducing infections caused by respiratory syncytial virus, bocavirus, and adenovirus in addition to acute otitis media bacterial pathogens.

  12. Usefulness of clinical data and rapid diagnostic tests to identify bacterial etiology in adult respiratory infections

    Directory of Open Access Journals (Sweden)

    Pilar Toledano-Sierra

    2015-01-01

    Full Text Available Respiratory tract infections are a common complaint and most of them, such as common cold and laryngitis, are viral in origin, so antibiotic use should be exceptional. However, there are other respiratory tract infections (sinusitis, pharyngitis, lower respiratory tract infections, and exacerbations of chronic obstructive pulmonary disease where a bacterial etiology is responsible for a non-negligible percentage, and antibiotics are often empirically indicated. The aim of the study is to identify the strength of the data obtained from the symptoms, physical examination and rapid diagnostic methods in respiratory infections in which antibiotic use is frequently proposed in order to improve diagnosis and influence the decision to prescribe these drugs. The review concludes that history, physical examination and rapid tests are useful to guide the need for antibiotic treatment in diseases such as acute sinusitis, acute pharyngitis, exacerbation of lower respiratory tract infection and chronic obstructive pulmonary disease. However, no isolated data is accurate enough by itself to confirm or rule out the need for antibiotics. Therefore, clinical prediction rules bring together history and physical examination, thereby improving the accuracy of the decision to indicate or not antibiotics.

  13. Distinct immune responses of juvenile and adult oysters (Crassostrea gigas) to viral and bacterial infections.

    Science.gov (United States)

    Green, Timothy J; Vergnes, Agnes; Montagnani, Caroline; de Lorgeril, Julien

    2016-01-01

    Since 2008, massive mortality events of Pacific oysters (Crassostrea gigas) have been reported worldwide and these disease events are often associated with Ostreid herpesvirus type 1 (OsHV-1). Epidemiological field studies have also reported oyster age and other pathogens of the Vibrio genus are contributing factors to this syndrome. We undertook a controlled laboratory experiment to simultaneously investigate survival and immunological response of juvenile and adult C. gigas at different time-points post-infection with OsHV-1, Vibrio tasmaniensis LGP32 and V. aestuarianus. Our data corroborates epidemiological studies that juveniles are more susceptible to OsHV-1, whereas adults are more susceptible to Vibrio. We measured the expression of 102 immune-genes by high-throughput RT-qPCR, which revealed oysters have different transcriptional responses to OsHV-1 and Vibrio. The transcriptional response in the early stages of OsHV-1 infection involved genes related to apoptosis and the interferon-pathway. Transcriptional response to Vibrio infection involved antimicrobial peptides, heat shock proteins and galectins. Interestingly, oysters in the later stages of OsHV-1 infection had a transcriptional response that resembled an antibacterial response, which is suggestive of the oyster's microbiome causing secondary infections (dysbiosis-driven pathology). This study provides molecular evidence that oysters can mount distinct immune response to viral and bacterial pathogens and these responses differ depending on the age of the host.

  14. Quercetin-induced apoptosis prevents EBV infection.

    Science.gov (United States)

    Lee, Minjung; Son, Myoungki; Ryu, Eunhyun; Shin, Yu Su; Kim, Jong Gwang; Kang, Byung Woog; Cho, Hyosun; Kang, Hyojeung

    2015-05-20

    Epstein-Barr virus (EBV) is a human gamma-1 herpesvirus that establishes a lifelong latency in over 90% of the world's population. During latency, virus exists predominantly as a chromatin-associated, multicopy episome in the nuclei of a variety of tumor cells derived from B cells, T cells, natural killer (NK) cells, and epithelial cells. Licorice is the root of Glycyrrhiza uralensis or G. glabra that has traditionally cultivated in eastern part of Asia. Licorice was reported to have anti-viral, anti-inflammatory, anti-atopic, hepatoprotective, anti-neurodegenerative, anti-tumor, anti-diabetic effects and so forth. Quercetin and isoliquiritigenin are produced from licorice and highly similar in molecular structure. They have diverse bioactive effects such as antiviral activity, anti-asthmatic activity, anti-cancer activity, anti-inflammation activity, monoamine-oxidase inhibitor, and etc. To determine anti-EBV and anti-EBVaGC (Epstein-Barr virus associated gastric carcinoma) effects of licorice, we investigated antitumor and antiviral effects of quercetin and isoliquiritigenin against EBVaGC. Although both quercetin and isoliquiritigenin are cytotoxic to SNU719 cells, quercetin induced more apoptosis in SNU719 cells than isoliquiritigenin, more completely eliminated DNMT1 and DNMT3A expressions than isoliquiritigenin, and more strongly affects the cell cycle progression of SNU719 than isoliquiritigenin. Both quercetin and isoliquiritigenin induce signal transductions to stimulate apoptosis, and induce EBV gene transcription. Quercetin enhances frequency of F promoter use, whereas isoliquiritigenin enhances frequency of Q promoter use. Quercetin reduces EBV latency, whereas isoliquiritigenin increases the latency. Quercetin increases more the EBV progeny production, and inhibits more EBV infection than isoliquiritigenin. These results indicate that quercetin could be a promising candidate for antiviral and antitumor agents against EBV and human gastric carcinoma.

  15. Bacterial infection as a likely cause of adverse reactions to polyacrylamide hydrogel fillers in cosmetic surgery

    DEFF Research Database (Denmark)

    Christensen, Lise; Breiting, Vibeke; Bjarnsholt, Thomas

    2013-01-01

    Background. The etiology of long-lasting adverse reactions to gel fillers used in cosmetic surgery is not known. Bacterial infection and immunological reaction to the product have been suggested. Methods. We performed a case-control study, with 77 biopsies and 30 cytology specimens originating from...... in the presence of polyacrylamide filler in cosmetic surgery, possibly due to a biofilm mode of growth. Adequate skin preparation and use of sterile technique in these procedures are mandatory, but antibiotic prophylaxis prior to injection of nondegradable gels like polyacrylamide should be explored as well....

  16. Synthetic Cationic Peptide IDR-1002 Provides Protection against Bacterial Infections through Chemokine Induction and Enhanced Leukocyte Recruitment

    DEFF Research Database (Denmark)

    Nijnik, Anastasia; Madera, Laurence; Ma, Shuhua;

    2010-01-01

    activity and diverse immunomodulatory properties. We have previously developed an innate defense regulator (IDR) 1, with protective activity against bacterial infection mediated entirely through its effects on the immunity of the host, as a novel approach to anti-infective therapy. In this study...... aureus-invasive infection model, with a >5-fold reduction in the protective dose in direct comparison with IDR-1. IDR-1002 also afforded protection against the Gram-negative bacterial pathogen Escherichia coli. Chemokine induction by IDR-1002 was found to be mediated through a Gi-coupled receptor...

  17. Infection-induced viscerosensory signals from the gut enhance anxiety: implications for psychoneuroimmunology.

    Science.gov (United States)

    Goehler, Lisa E; Lyte, Mark; Gaykema, Ronald P A

    2007-08-01

    Infection and inflammation lead to changes in mood and cognition. Although the "classic" sickness behavior syndrome, involving fatigue, social withdrawal, and loss of appetites are most familiar, other emotional responses accompany immune activation, including anxiety. Recent studies have shown that gastrointestinal bacterial infections lead to enhanced anxiety-like behavior in mice. The bacteria-induced signal is most likely carried by vagal sensory neurons, and occurs early on (within 6h) during the infection. These signals induce evidence of activation in brain regions that integrate viscerosensory information with mood, and potentiate activation in brain regions established as key players in fear and anxiety. The findings underline the importance of viscerosensory signals arising from the gastrointestinal tract in modulation of behaviors appropriate for coping with threats, and suggest that these signals may contribute to affective symptoms associated with gastrointestinal disorders.

  18. A bacterial quorum-sensing precursor induces mortality in the marine coccolithophore, Emiliania huxleyi

    Directory of Open Access Journals (Sweden)

    Elizabeth L Harvey

    2016-02-01

    Full Text Available Interactions between phytoplankton and bacteria play a central role in mediating biogeochemical cycling and food web structure in the ocean. However, deciphering the chemical drivers of these interspecies interactions remains challenging. Here we report the isolation of 2-heptyl-4-quinolone (HHQ, released by Pseudoalteromonas piscicida, a marine gamma-proteobacteria previously reported to induce phytoplankton mortality through a hitherto unknown algicidal mechanism. HHQ functions as both an antibiotic and a bacterial signaling molecule in cell-cell communication in clinical infection models. Co-culture of the bloom-forming coccolithophore, Emiliania huxleyi with both live P. piscicida and cell-free filtrates caused a significant decrease in algal growth. Investigations of the P. piscicida exometabolome revealed HHQ, at nanomolar concentrations, induced mortality in three strains of E. huxleyi. Mortality of E. huxleyi in response to HHQ occurred slowly, implying static growth rather than a singular loss event (e.g. rapid cell lysis. In contrast, the marine chlorophyte, Dunaliella tertiolecta and diatom, Phaeodactylum tricornutum were unaffected by HHQ exposures. These results suggest that HHQ mediates the type of interkingdom interactions that cause shifts in phytoplankton population dynamics. These chemically mediated interactions, and other like it, ultimately influence large-scale oceanographic processes.

  19. Ceragenins – a new weapon to fight multidrug resistant bacterial infections

    Directory of Open Access Journals (Sweden)

    Urszula Surel

    2014-09-01

    Full Text Available Growing antibiotic resistance among pathogenic microorganisms is one of the most challenging problems. Often, a single mutation in a bacterial cell leads to the formation of a new drug resistance mechanism. The ceragenins are a novel class of antibiotic, offering great promise in future treatment of infections. These cationic antimicrobial lipids are net positively charged cholic acid derivates that are electrostatically attracted to the negatively charged membranes of bacteria, certain viruses, fungi, and protozoa. After membrane insertion, they interfere with membrane organisation, resulting in membrane dysfunction and cell death. This review focuses on the broad spectrum of antibacterial activity of ceragenins, and their potential to become a new group of antibiotics for prevention and treatment of infections, especially those caused by multidrug-resistant bacteria.

  20. Bacterial infections from aquatic species: potential for and prevention of contact zoonoses.

    Science.gov (United States)

    Haenen, O L M; Evans, J J; Berthe, F

    2013-08-01

    As aquaculture production and the consumption of aquaculture products increase, the possibility of contracting zoonotic infections from either handling or ingesting these products also increases. The principal pathogens acquired topically from fish or shellfish through spine/pincer puncture or open wounds are Aeromonas hydrophila, Edwardsiella tarda, Mycobacterium marinum, Streptococcus iniae, Vibrio vulnificus and V. damsela. These pathogens, which are all indigenous to the aquatic environment, have also been associated with disease outbreaks in food fish. Outbreaks are often related to management factors, such as the quality and quantity of nutrients in the water and high stocking density, which can increase bacterial loads on the external surface of the fish. As a result, diseased fish are more likely to transmit infection to humans. This review provides an account of human cases of zoonoses throughout the world from the principal zoonotic pathogens of fish and shellfish.

  1. Finding immune gene expression differences induced by marine bacterial pathogens in the deep-sea hydrothermal vent mussel Bathymodiolus azoricus

    Directory of Open Access Journals (Sweden)

    R. Bettencourt

    2013-02-01

    Full Text Available The deep-sea hydrothermal vent mussel Bathymodiolus azoricus lives in a natural environment characterized by extreme conditions of hydrostatic pressure, temperature, pH, high concentrations of heavy metals, methane and hydrogen sulphide. The deep-sea vent biological systems represent thus the opportunity to study and provide new insights into the basic physiological principles that govern the defense mechanisms in vent animals and to understand how they cope with microbial infections. Hence, the importance of understanding this animal's innate defense mechanisms, by examining its differential immune gene expressions toward different pathogenic agents. In the present study, B. azoricus mussels were infected with single suspensions of marine bacterial pathogens, consisting of Vibrio splendidus, Vibrio alginolyticus, or Vibrio anguillarum, and a pool of these Vibrio strains. Flavobacterium suspensions were also used as an irrelevant bacterium. Gene expression analyses were carried out using gill samples from animals dissected at 12 h and 24 h post-infection times by means of quantitative-Polymerase Chain Reaction aimed at targeting several immune genes. We also performed SDS-PAGE protein analyses from the same gill tissues. We concluded that there are different levels of immune gene expression between the 12 h and 24 h exposure times to various bacterial suspensions. Our results from qPCR demonstrated a general pattern of gene expression, decreasing from 12 h over 24 h post-infection. Among the bacteria tested, Flavobacterium is the microorganism species inducing the highest gene expression level in 12 h post-infections animals. The 24 h infected animals revealed, however, greater gene expression levels, using V. splendidus as the infectious agent. The SDS-PAGE analysis also pointed at protein profile differences between 12 h and 24 h, particularly around a protein area, of 18 KDa molecular mass, where most dissimilarities were found. Multivariate

  2. Morphine induces bacterial translocation in mice by compromising intestinal barrier function in a TLR-dependent manner.

    Directory of Open Access Journals (Sweden)

    Jingjing Meng

    Full Text Available Opiates are among the most prescribed drugs for pain management. However, morphine use or abuse results in significant gut bacterial translocation and predisposes patients to serious infections with gut origin. The mechanism underlying this defect is still unknown. In this report, we investigated the mechanisms underlying compromised gut immune function and bacterial translocation following morphine treatment. We demonstrate significant bacterial translocation to mesenteric lymph node (MLN and liver following morphine treatment in wild-type (WT animals that was dramatically and significantly attenuated in Toll-like receptor (TLR2 and 4 knockout mice. We further observed significant disruption of tight junction protein organization only in the ileum but not in the colon of morphine treated WT animals. Inhibition of myosin light chain kinase (MLCK blocked the effects of both morphine and TLR ligands, suggesting the role of MLCK in tight junction modulation by TLR. This study conclusively demonstrates that morphine induced gut epithelial barrier dysfunction and subsequent bacteria translocation are mediated by TLR signaling and thus TLRs can be exploited as potential therapeutic targets for alleviating infections and even sepsis in morphine-using or abusing populations.

  3. Aerobic bacterial profile and antibiotic resistance in patients with diabetic foot infections

    Directory of Open Access Journals (Sweden)

    Michele Cezimbra Perim

    2015-10-01

    Full Text Available ABSTRACTINTRODUCTION: This study aimed to determine the frequencies of bacterial isolates cultured from diabetic foot infections and assess their resistance and susceptibility to commonly used antibiotics.METHODS: This prospective study included 41 patients with diabetic foot lesions. Bacteria were isolated from foot lesions, and their antibiotic susceptibility pattern was determined using the Kirby-Bauer disk diffusion method and/or broth method [minimum inhibitory concentration (MIC].RESULTS: The most common location of ulceration was the toe (54%, followed by the plantar surface (27% and dorsal portion (19%. A total of 89 bacterial isolates were obtained from 30 patients. The infections were predominantly due to Gram-positive bacteria and polymicrobial bacteremia. The most commonly isolated Gram-positive bacteria were Staphylococcus aureus, followed by Staphylococcus saprophyticus, Staphylococcus epidermidis, Streptococcus agalactiae, and Streptococcus pneumoniae. The most commonly isolated Gram-negative bacteria were Proteus spp. and Enterobacterspp., followed by Escherichia coli, Pseudomonasspp., and Citrobacterspp. Nine cases of methicillin-resistant Staphylococcus aureus (MRSA had cefoxitin resistance, and among these MRSA isolates, 3 were resistant to vancomycin with the MIC technique. The antibiotic imipenem was the most effective against both Gram-positive and Gram-negative bacteria, and gentamicin was effective against Gram-negative bacteria.CONCLUSIONS: The present study confirmed the high prevalence of multidrug-resistant pathogens in diabetic foot ulcers. It is necessary to evaluate the different microorganisms infecting the wound and to know the antibiotic susceptibility patterns of the isolates from the infected wound. This knowledge is crucial for planning treatment with the appropriate antibiotics, reducing resistance patterns, and minimizing healthcare costs.

  4. Ascites bacterial burden and immune cell profile are associated with poor clinical outcomes in the absence of overt infection.

    Directory of Open Access Journals (Sweden)

    Kevin J Fagan

    Full Text Available Bacterial infections, most commonly spontaneous bacterial peritonitis in patients with ascites, occur in one third of admitted patients with cirrhosis, and account for a 4-fold increase in mortality. Bacteria are isolated from less than 40% of ascites infections by culture, necessitating empirical antibiotic treatment, but culture-independent studies suggest bacteria are commonly present, even in the absence of overt infection. Widespread detection of low levels of bacteria in ascites, in the absence of peritonitis, suggests immune impairment may contribute to higher susceptibility to infection in cirrhotic patients. However, little is known about the role of ascites leukocyte composition and function in this context. We determined ascites bacterial composition by quantitative PCR and 16S rRNA gene sequencing in 25 patients with culture-negative, non-neutrocytic ascites, and compared microbiological data with ascites and peripheral blood leukocyte composition and phenotype. Bacterial DNA was detected in ascitic fluid from 23 of 25 patients, with significant positive correlations between bacterial DNA levels and poor 6-month clinical outcomes (death, readmission. Ascites leukocyte composition was variable, but dominated by macrophages or T lymphocytes, with lower numbers of B lymphocytes and natural killer cells. Consistent with the hypothesis that impaired innate immunity contributes to susceptibility to infection, high bacterial DNA burden was associated with reduced major histocompatibility complex class II expression on ascites (but not peripheral blood monocytes/macrophages. These data indicate an association between the presence of ascites bacterial DNA and early death and readmission in patients with decompensated cirrhosis. They further suggest that impairment of innate immunity contributes to increased bacterial translocation, risk of peritonitis, or both.

  5. Demodex-associated bacterial proteins induce neutrophil activation.

    LENUS (Irish Health Repository)

    2012-02-01

    Background: Patients with rosacea demonstrate a higher density of Demodex mites in their skin than controls. A bacterium isolated from a Demodex mite from a patient with papulopustular rosacea (PPR) was previously shown to provoke an immune response in patients with PPR or ocular rosacea thus suggesting a possible role for bacterial proteins in the etiology of this condition. Objectives: To examine the response of neutrophils to proteins derived from a bacterium isolated from a Demodex mite. Methods: Bacterial cells were lysed and proteins were partially purified by AKTA-FPLC. Isolated neutrophils were exposed to bacterial proteins and monitored for alterations in migration, degranulation and cytokine production. Results: Neutrophils exposed to proteins from Bacillus cells demonstrated increased levels of migration and elevated release of MMP-9, an enzyme known to degrade collagen and cathelicidin, an antimicrobial peptide. In addition neutrophils exposed to the bacterial proteins demonstrated elevated rates of Il-8 and TNF-alpha production. Conclusions: Proteins produced by a bacterium isolated from a Demodex mite have the ability to increase the migration, degranulation and cytokine production abilities of neutrophils. These results suggest that bacteria may play a role in the inflammatory erythema associated with rosacea.

  6. Helicobacter pylori infection: An overview of bacterial virulence factors and pathogenesis

    Directory of Open Access Journals (Sweden)

    Cheng-Yen Kao

    2016-02-01

    Full Text Available Helicobacter pylori pathogenesis and disease outcomes are mediated by a complex interplay between bacterial virulence factors, host, and environmental factors. After H. pylori enters the host stomach, four steps are critical for bacteria to establish successful colonization, persistent infection, and disease pathogenesis: (1 Survival in the acidic stomach; (2 movement toward epithelium cells by flagella-mediated motility; (3 attachment to host cells by adhesins/receptors interaction; (4 causing tissue damage by toxin release. Over the past 20 years, the understanding of H. pylori pathogenesis has been improved by studies focusing on the host and bacterial factors through epidemiology researches and molecular mechanism investigations. These include studies identifying the roles of novel virulence factors and their association with different disease outcomes, especially the bacterial adhesins, cag pathogenicity island, and vacuolating cytotoxin. Recently, the development of large-scale screening methods, including proteomic, and transcriptomic tools, has been used to determine the complex gene regulatory networks in H. pylori. In addition, a more available complete genomic database of H. pylori strains isolated from patients with different gastrointestinal diseases worldwide is helpful to characterize this bacterium. This review highlights the key findings of H. pylori virulence factors reported over the past 20 years.

  7. Bacterial etiology of bloodstream infections and antimicrobial resistance in Dhaka, Bangladesh, 2005–2014

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    Dilruba Ahmed

    2017-01-01

    Full Text Available Abstract Background Bloodstream infections due to bacterial pathogens are a major cause of morbidity and mortality in Bangladesh and other developing countries. In these countries, most patients are treated empirically based on their clinical symptoms. Therefore, up to date etiological data for major pathogens causing bloodstream infections may play a positive role in better healthcare management. The aim of this study was to identify the bacterial pathogens causing major bloodstream infections in Dhaka, Bangladesh and determine their antibiotic susceptibility pattern. Methods From January 2005 to December 2014, a total of 103,679 single bottle blood samples were collected from both hospitalized and domiciliary patients attending Dhaka hospital, icddrb, Bangladesh All the blood samples were processed for culture using a BACT/Alert blood culture machine. Further identification of bacterial pathogens and their antimicrobial susceptibility test were performed using standard microbiological procedures. Results Overall, 13.6% of the cultured blood samples were positive and Gram-negative (72.1% bacteria were predominant throughout the study period. Salmonella Typhi was the most frequently isolated organism (36.9% of samples in this study and a high percentage of those strains were multidrug-resistant (MDR. However, a decreasing trend in the S. Typhi isolation rate was observed and, noticeably, the percentage of MDR S. Typhi isolated declined sharply over the study period. An overall increase in the presence of Gram-positive bacteria was observed, but most significantly we observed the percentage of MDR Gram-positive bacteria to double over the study period. Overall, Gram positive bacteria were more resistant to most of the commonly used antibiotics than Gram-negative bacteria, but the MDR level was high in both groups. Conclusions This study identified the major bacterial pathogens involved with BSI in Dhaka, Bangladesh and also revealed their

  8. Preliminary molecular analysis of bacterial composition in periapical lesions with primary endodontic infections of deciduous teeth

    Institute of Scientific and Technical Information of China (English)

    SHANG Jia-jian; YANG Qiu-bo; ZHAO Huan-ying; CAI Shuang; ZHOU Yan; SUN Zheng

    2013-01-01

    Background The bacterial composition of periapical lesions in deciduous teeth has not been well documented.This study was designed to explore the bacterial compositions,especially the dominant bacteria in periapical lesions using 16S rRNA sequencing.Methods Tissue samples were collected from 11 periapical lesions in deciduous teeth with primary endodontic infections.DNA was extracted from each sample and analyzed using 16S rRNA cloning and sequencing for the identification of bacteria.Results All DNA samples were positive for 16S rRNA gene PCR.One hundred and fifty-one phylotypes from 810 clones were identified to eight phyla,and each sample contained an average of 25.9 phylotypes.In addition,59 phylotypes were detected in more than two samples,and Fusobacterium (F.) nucleatum (8/11),Dialister (D.) invisus (8/11),Campylobacter (C.) gracilis (7/11),Escherichia (E.) coil DH1 (6/11),Aggregatibacter (A.) segnis (6/11),and Streptococcus (S.) mitis (6/11) were the most prevalent species.Furthermore,45 as-yet-uncultivated phylotypes were also identified.Conclusions Chronic periapical lesions in deciduous teeth contained polymicrobial infections.F.nucleatum,D.invisus,C.gracilis,E.coli DH1,A.segnis,and S.mitis were the most prevalent species detected by 16S rRNA sequencing.

  9. Hyperglycemia Impairs Neutrophil-Mediated Bacterial Clearance in Mice Infected with the Lyme Disease Pathogen.

    Directory of Open Access Journals (Sweden)

    Ashkan Javid

    Full Text Available Insulin-insufficient type 1 diabetes is associated with attenuated bactericidal function of neutrophils, which are key mediators of innate immune responses to microbes as well as pathological inflammatory processes. Neutrophils are central to immune responses to the Lyme pathogen Borrelia burgdorferi. The effect of hyperglycemia on host susceptibility to and outcomes of B. burgdorferi infection has not been examined. The present study investigated the impact of sustained obesity-independent hyperglycemia in mice on bacterial clearance, inflammatory pathology and neutrophil responses to B. burgdorferi. Hyperglycemia was associated with reduced arthritis incidence but more widespread tissue colonization and reduced clearance of bacterial DNA in multiple tissues including brain, heart, liver, lung and knee joint. B. burgdorferi uptake and killing were impaired in neutrophils isolated from hyperglycemic mice. Thus, attenuated neutrophil function in insulin-insufficient hyperglycemia was associated with reduced B. burgdorferi clearance in target organs. These data suggest that investigating the effects of comorbid conditions such as diabetes on outcomes of B. burgdorferi infections in humans may be warranted.

  10. Photodynamic antimicrobial chemotherapy using zinc phthalocyanine derivative for bacterial skin infection

    Science.gov (United States)

    Chen, Zhuo; Zhang, Yaxin; Li, Linsen; Zhou, Shanyong; Chen, Jincan; Hu, Ping; Huang, Mingdong

    2014-09-01

    Folliculitis, furunculosis and acne vulgaris are very common skin disorders of the hair follicles and are associated with large grease-producing (sebaceous) glands. Although the detailed mechanisms involved these skin disorders are not fully understood, it is believed that the bacteria Propionibacterium acnes and Staphylococcus aureus are the key pathogenic factors involved. Conventional treatments targeting the pathogenic factors include a variety of topical and oral medications such as antibiotics. The wide use of antibiotics leads to bacterial resistance, and hence there is a need for new alternatives in above bacterial skin treatment. Photodynamic antimicrobial chemotherapy (PACT) is based on an initial photosensitization of the infected area, followed by irradiation with visible light, producing singlet oxygen which is cytotoxic to bacteria. Herein we reported a zinc phthalocyanine derivative, pentalysine β-carbonylphthalocyanine zinc (ZnPc-(Lys)5) and its PACT effect for the bacteria involved in these skin infections. Our results demonstrated strong bactericidal effects of this photosensitizer on both strains of the bacteria, suggesting ZnPc-(Lys)5 as a promising antimicrobial photosensitizer for the treatment of infectious diseases caused by these bacteria.

  11. The Risk of Serious Bacterial Infection in Neutropenic Immunocompetent Febrile Children.

    Science.gov (United States)

    Barg, Assaf A; Kozer, Eran; Mordish, Yair; Lazarovitch, Tsilia; Kventsel, Iris; Goldman, Michael

    2015-08-01

    Only few reports have looked into the risk of invasive bacterial infection in children with neutropenia that is not malignancy related. The objective of the current study was to determine the clinical significance of neutropenia as a predictor of serious bacterial infection (SBI) in immunocompetent children. We conducted a retrospective case-control study including children 3 months to 18 years of age with fever ≥ 38°C hospitalized or presenting to the emergency department. Patients who had neutropenia ≤ 1000 ANC/μL and had a blood culture taken were matched for age with the consecutive febrile patients for whom a blood culture was taken. The main outcome was the rate of SBI. SBIs were more prevalent among the control group than in the group of children with neutropenia, 19/71 and 6/71, respectively (P = 0.0005). More children were treated with antibiotics among the control group than in the group of children with neutropenia, 39/71 and 20/71, respectively (P neutropenia do not carry a higher risk for SBIs compared with patients with fever who do not have neutropenia.

  12. Transcriptional profiling at different sites in lungs of pigs during acute bacterial respiratory infection

    DEFF Research Database (Denmark)

    Mortensen, Shila; Skovgaard, Kerstin; Hedegaard, Jakob

    2011-01-01

    The local transcriptional response was studied in different locations of lungs from pigs experimentally infected with the respiratory pathogen Actinobacillus pleuropneumoniae serotype 5B, using porcine cDNA microarrays. This infection gives rise to well-demarcated infection loci in the lung...... of apoptosis and the complement system. Interferon-g was downregulated in both necrotic and bordering areas. Evidence of neutrophil recruitment was seen by the up-regulation of chemotactic factors for neutrophils. In conclusion, we found subsets of genes expressed at different levels in the three selected...... of induced genes as, in unaffected areas a large part of differently expressed genes were involved in systemic reactions to infections, while differently expressed genes in necrotic areas were mainly concerned with homeostasis regulation....

  13. Pre-infection physical exercise decreases mortality and stimulates neurogenesis in bacterial meningitis

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    Liebetanz David

    2012-07-01

    Full Text Available Abstract Physical exercise has been shown to increase neurogenesis, to decrease neuronal injury and to improve memory in animal models of stroke and head trauma. Therefore, we investigated the effect of voluntary wheel running on survival, neuronal damage and cell proliferation in a mouse model of pneumococcal meningitis. Mice were housed in cages equipped with voluntary running wheels or in standard cages before induction of bacterial meningitis by a subarachnoid injection of a Streptococcus pneumoniae type 3 strain. 24 hours later antibiotic treatment was initiated with ceftriaxone (100 mg/kg twice daily. Experiments were terminated either 30 hours or 4 days (short-term or 7 weeks (long-term after infection, and the survival time, inflammatory cytokines and corticosterone levels, neurogenesis in the dentate gyrus of the hippocampal formation and the cognitive function were evaluated in surviving mice. Survival time was significantly increased in running mice compared to control animals (p = 0.0087 in short-term and p = 0.016 in long-term experiments, log-rank test. At the end of the long-term experiment, mortality was lower in trained than in sedentary animals (p = 0.031, Fisher’s Exact test. Hippocampal neurogenesis – assessed by the density of doublecortin-, TUC-4- and BrdU + NeuN-colabeled cells - was significantly increased in running mice in comparison to the sedentary group after meningitis. However, Morris water maze performance of both groups 6 weeks after bacterial meningitis did not reveal differences in learning ability. In conclusion, physical exercise prior to infection increased survival in a mouse model of bacterial meningitis and stimulated neurogenesis in the dentate gyrus of the hippocampal formation.

  14. Elevated carbon monoxide in the exhaled breath of mice during a systemic bacterial infection.

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    Alan G Barbour

    Full Text Available Blood is the specimen of choice for most laboratory tests for diagnosis and disease monitoring. Sampling exhaled breath is a noninvasive alternative to phlebotomy and has the potential for real-time monitoring at the bedside. Improved instrumentation has advanced breath analysis for several gaseous compounds from humans. However, application to small animal models of diseases and physiology has been limited. To extend breath analysis to mice, we crafted a means for collecting nose-only breath samples from groups and individual animals who were awake. Samples were subjected to gas chromatography and mass spectrometry procedures developed for highly sensitive analysis of trace volatile organic compounds (VOCs in the atmosphere. We evaluated the system with experimental systemic infections of severe combined immunodeficiency Mus musculus with the bacterium Borrelia hermsii. Infected mice developed bacterial densities of ∼10(7 per ml of blood by day 4 or 5 and in comparison to uninfected controls had hepatosplenomegaly and elevations of both inflammatory and anti-inflammatory cytokines. While 12 samples from individual infected mice on days 4 and 5 and 6 samples from uninfected mice did not significantly differ for 72 different VOCs, carbon monoxide (CO was elevated in samples from infected mice, with a mean (95% confidence limits effect size of 4.2 (2.8-5.6, when differences in CO2 in the breath were taken into account. Normalized CO values declined to the uninfected range after one day of treatment with the antibiotic ceftriaxone. Strongly correlated with CO in the breath were levels of heme oxygenase-1 protein in serum and HMOX1 transcripts in whole blood. These results (i provide further evidence of the informativeness of CO concentration in the exhaled breath during systemic infection and inflammation, and (ii encourage evaluation of this noninvasive analytic approach in other various other rodent models of infection and for utility in

  15. Molecular Imaging of Bacterial Infections in vivo: The Discrimination between Infection and Inflammation

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    Heather Eggleston

    2014-05-01

    Full Text Available Molecular imaging by definition is the visualization of molecular and cellular processes within a given system. The modalities and reagents described here represent a diverse array spanning both pre-clinical and clinical applications. Innovations in probe design and technologies would greatly benefit therapeutic outcomes by enhancing diagnostic accuracy and assessment of acute therapy. Opportunistic pathogens continue to pose a worldwide threat, despite advancements in treatment strategies, which highlights the continued need for improved diagnostics. In this review, we present a summary of the current clinical protocol for the imaging of a suspected infection, methods currently in development to optimize this imaging process, and finally, insight into endocarditis as a model of infectious disease in immediate need of improved diagnostic methods.

  16. Changes in gastric microbiota induced by Helicobacter pylori infection and preventive effects of Lactobacillus plantarum ZDY 2013 against such infection.

    Science.gov (United States)

    Pan, Mingfang; Wan, Cuixiang; Xie, Qiong; Huang, Renhui; Tao, Xueying; Shah, Nagendra P; Wei, Hua

    2016-02-01

    Helicobacter pylori is a gram-negative pathogen linked to gastric ulcers and stomach cancer. Gastric microbiota might play an essential role in the pathogenesis of these stomach diseases. In this study, we investigated the preventive effect of a probiotic candidate Lactobacillus plantarum ZDY 2013 as a protective agent against the gastric mucosal inflammation and alteration of gastric microbiota induced by H. pylori infection in a mouse model. Prior to infection, mice were pretreated with or without 400 µL of L. plantarum ZDY 2013 at a concentration of 10(9) cfu/mL per mouse. At 6 wk postinfection, gastric mucosal immune response and alteration in gastric microbiota mice were examined by quantitative real-time PCR and high-throughput 16S rRNA gene amplicon sequencing, respectively. The results showed that L. plantarum ZDY 2013 pretreatment prevented increase in inflammatory cytokines (e.g., IL-1β and IFN-γ) and inflammatory cell infiltration in gastric lamina propria induced by H. pylori infection. Weighted UniFrac principal coordinate analysis showed that L. plantarum ZDY 2013 pretreatment prevented the alteration in gastric microbiota post-H. pylori infection. Linear discriminant analysis coupled with effect size identified 22 bacterial taxa (e.g., Pasteurellaceae, Erysipelotrichaceae, Halomonadaceae, Helicobacteraceae, and Spirochaetaceae) that overgrew in the gastric microbiota of H. pylori-infected mice, and most of them belonged to the Proteobacteria phylum. Lactobacillus plantarum ZDY 2013 pretreatment prevented this alteration; only 6 taxa (e.g., Lachnospiraceae, Ruminococcaceae, and Clostridiaceae), mainly from the taxa of Firmicutes and Bacteroidetes, were dominant in the gastric microbiota of the L. plantarum ZDY 2013 pretreated mice. Administration of L. plantarum ZDY 2013 for 3 wk led to increase in several bacterial taxa (e.g., Rikenella, Staphylococcus, Bifidobacterium), although a nonsignificant alteration was found in the gastric microbiota

  17. Disease interactions in a shared host plant: effects of pre-existing viral infection on cucurbit plant defense responses and resistance to bacterial wilt disease.

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    Lori R Shapiro

    Full Text Available Both biotic and abiotic stressors can elicit broad-spectrum plant resistance against subsequent pathogen challenges. However, we currently have little understanding of how such effects influence broader aspects of disease ecology and epidemiology in natural environments where plants interact with multiple antagonists simultaneously. In previous work, we have shown that healthy wild gourd plants (Cucurbita pepo ssp. texana contract a fatal bacterial wilt infection (caused by Erwinia tracheiphila at significantly higher rates than plants infected with Zucchini yellow mosaic virus (ZYMV. We recently reported evidence that this pattern is explained, at least in part, by reduced visitation of ZYMV-infected plants by the cucumber beetle vectors of E. tracheiphila. Here we examine whether ZYMV-infection may also directly elicit plant resistance to subsequent E. tracheiphila infection. In laboratory studies, we assayed the induction of key phytohormones (SA and JA in single and mixed infections of these pathogens, as well as in response to the feeding of A. vittatum cucumber beetles on healthy and infected plants. We also tracked the incidence and progression of wilt disease symptoms in plants with prior ZYMV infections. Our results indicate that ZYMV-infection slightly delays the progression of wilt symptoms, but does not significantly reduce E. tracheiphila infection success. This observation supports the hypothesis that reduced rates of wilt disease in ZYMV-infected plants reflect reduced visitation by beetle vectors. We also documented consistently strong SA responses to ZYMV infection, but limited responses to E. tracheiphila in the absence of ZYMV, suggesting that the latter pathogen may effectively evade or suppress plant defenses, although we observed no evidence of antagonistic cross-talk between SA and JA signaling pathways. We did, however, document effects of E. tracheiphila on induced responses to herbivory that may influence host

  18. Why Children with Severe Bacterial Infection Die: A Population–Based Study of Determinants and Consequences of Suboptimal Care with a Special Emphasis on Methodological Issues

    OpenAIRE

    Elise Launay; Christèle Gras-Le Guen; Alain Martinot; Rémy Assathiany; Elise Martin; Thomas Blanchais; Catherine Deneux-Tharaux; Jean-Christophe Rozé; Martin Chalumeau

    2014-01-01

    INTRODUCTION: Suboptimal care is frequent in the management of severe bacterial infection. We aimed to evaluate the consequences of suboptimal care in the early management of severe bacterial infection in children and study the determinants. METHODS: A previously reported population-based confidential enquiry included all children (3 months- 16 years) who died of severe bacterial infection in a French area during a 7-year period. Here, we compared the optimality of the management of these cas...

  19. STUDIES ON THE BLOOD PROTEINS : I. THE SERUM GLOBULINS IN BACTERIAL INFECTION AND IMMUNITY.

    Science.gov (United States)

    Hurwitz, S H; Meyer, K F

    1916-11-01

    The progress of an infection is usually associated with marked changes in the serum proteins. There may be an increase in the percentage of the total protein during some stage of the infection, and there is usually a change in the albumin-globulin ratio with an increase in the total globulins. This rise may antedate the development of any resistance by a considerable period of time. The non-protein constituents of the blood show fluctuations with a tendency to rise as the infection progresses. The process of immunization is in almost all instances associated with a definite increase in the globulins of the blood, and in some cases with a complete inversion of the normal albumin-globulin ratio. This may be produced both by living and dead organisms and by bacterial endotoxins. Massive doses usually result in an upset which shows no tendency to right itself during the period of observation. A rise in the globulins has been shown to occur long before the animal develops immune bodies in any appreciable concentration; and where the globulin curve and antibody curve appear to parallel one another, it can be shown by a careful analysis of both curves that there is a definite lack of correspondence at various periods of the experiment. Animals possessing a basic immunity show a more rapid rise in the globulin curve following inoculation. There is no parallelism between the leukocytic reaction and the globulin reaction. During periods of leukopenia the globulins may be as high as during the period of a leukocytosis. Bacterial endotoxins produce as striking an increase in the serum globulins as do living and killed bacteria. This would seem to indicate that a bacterial invasion of the organism is not absolutely essential for the globulin changes, and that the toxogenic factor in infection and immunity must play a part in the production of the changes noted. Inflammatory irritants injected intraperitoneally also result in a globulin increase. In this case the changes

  20. Predictors of time to recovery in infants with probable serious bacterial infection.

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    Prashant Singh

    Full Text Available Serious bacterial infections continue to be an important cause of death and illness among infants in developing countries. Time to recovery could be considered a surrogate marker of severity of the infection. We therefore aimed to identify clinical and laboratory predictors of time to recovery in infants with probable serious bacterial infection (PSBI.We used the dataset of 700 infants (7-120 days enrolled in a randomised controlled trial in India in which 10mg of oral zinc or placebo was given to infants with PSBI. PSBI was defined as signs/symptoms of possible serious bacterial infection along with baseline C-reactive protein(CRP level >12mg/L. Time to recovery was defined as time from enrolment to the end of a 2-day period with no symptoms/signs of PSBI and daily weight gain of at least 10g over 2 succesive days on exclusive oral feeding. Cox proportional hazard regression was used to measure the associations between relevant variables and time to recovery.Infants who were formula fed prior to illness episode had 33% longer time to recovery (HR-0.67, 95%CI-0.52, 0.87 than those who were not. Being underweight (HR-0.84, 95%CI-0.70, 0.99, lethargic (HR-0.77, 95%CI-0.62, 0.96 and irritable (HR-0.81, 95%CI-0.66, 0.99 were independent predictors of time to recovery. Baseline CRP was significantly associated with time to recovery (P<0.001, higher CRP was associated with longer time to recovery and this association was nearly linear.Simple clinical and laboratory parameters such as formula feeding prior to the illness, being underweight, lethargic, irritable and having elevated CRP levels could be used for early identification of infants with PSBI at risk for protracted illness and could guide prompt referral to higher centers in resource limited settings. This also provides prognostic information to clinicians and family as longer recovery time has economic and social implications on the family in our setting.ClinicalTrials.gov NCT00347386.

  1. Biofilms bacterianos e infección Bacterial biofilms and infection

    Directory of Open Access Journals (Sweden)

    I. Lasa

    2005-08-01

    describe el papel que juegan los biofilms en infecciones humanas persistentes.In developed countries we tend to think of heart disease and the numerous forms of cancer as the main causes of mortality, but on a global scale infectious diseases come close, or may even be ahead: 14.9 million deaths in 2002 compared to cardiovascular diseases (16.9 million deaths and cancer (7.1 million deaths (WHO report 2004. The infectious agents responsible for human mortality have evolved as medical techniques and hygienic measures have changed. Modern-day acute infectious diseases caused by specialized bacterial pathogens such as diphtheria, tetanus, cholera, plague, which represented the main causes of death at the beginning of XX century, have been effectively controlled with antibiotics and vaccines. In their place, more than half of the infectious diseases that affect mildly immunocompromised patients involve bacterial species that are commensal with the human body; these can produce chronic infections, are resistant to antimicrobial agents and there is no effective vaccine against them. Examples of these infections are the otitis media, native valve endocarditis, chronic urinary infections, bacterial prostatitis, osteomyelitis and all the infections related to medical devices. Direct analysis of the surface of medical devices or of tissues that have been foci of chronic infections shows the presence of large numbers of bacteria surrounded by an exopolysaccharide matrix, which has been named the "biofilm". Inside the biofilm, bacteria grow protected from the action of the antibodies, phagocytic cells and antimicrobial treatments. In this article, we describe the role of bacterial biofilms in human persistent infections.

  2. A novel ion-beam-mutation effect application in identification of gene involved in bacterial antagonism to fungal infection of ornamental crops

    Energy Technology Data Exchange (ETDEWEB)

    Mahadtanapuk, S. [Faculty of Agriculture and Natural Resources, University of Phayao, Maeka, Muang, Phayao 56000 (Thailand); Teraarusiri, W. [Central Laboratory, University of Phayao, Maeka, Muang, Phayao 56000 (Thailand); Nanakorn, W. [The Crown Property Bureau, 173 Nakhonratchasrima Road, Dusit, Bangkok 10300 (Thailand); Yu, L.D., E-mail: yuld@thep-center.org [Plasma and Beam Physics Research Facility, Department of Physics and Materials Science, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Thailand Center of Excellence in Physics, Commission on Higher Education, 328 Si Ayutthaya Road, Bangkok 10400 (Thailand); Thongkumkoon, P. [Plasma and Beam Physics Research Facility, Department of Physics and Materials Science, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Anuntalabhochai, S., E-mail: soanu.1@gmail.com [Molecular Biology Laboratory, Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand)

    2014-05-01

    Highlights: • Ion beam bombardment induced mutation in bacterial B. licheniformis. • A mutant lost antifungal activity. • DNA fingerprint of the mutant was analyzed. • The lost gene was indentified to code for TrxR gene. • TrxR gene from B. licheniformis expressed the flower antagonism to fungi. - Abstract: This work is on a novel application of ion beam effect on biological mutation. Bacillus licheniformis (B. licheniformis) is a common soil bacterium with an antagonistic effect on Curcuma alismatifolia Gagnep. and Chrysanthemum indicum Linn. In an attempt to control fungal diseases of local crops by utilizing B. licheniformis, we carried out gene analysis of the bacterium to understand the bacterial antagonistic mechanism. The bacterial cells were bombarded to induce mutations using nitrogen ion beam. After ion bombardment, DNA analysis revealed that the modified polymorphism fragment present in the wild type was missing in a bacterial mutant which lost the antifungal activity. The fragments conserved in the wild type but lost in the mutant bacteria was identified to code for the thioredoxin reductase (TrxR) gene. The gene analysis showed that the TrxR gene from B. licheniformis had the expression of the antagonism to fungi in a synchronous time evolution with the fungus inhibition when the bacteria were co-cultivated with the fungi. The collective results indicate the TrxR gene responsible for the antagonism of bacteria B. licheniformis to fungal infection.

  3. A combination of independent transcriptional regulators shapes bacterial virulence gene expression during infection.

    Directory of Open Access Journals (Sweden)

    Samuel A Shelburne

    2010-03-01

    Full Text Available Transcriptional regulatory networks are fundamental to how microbes alter gene expression in response to environmental stimuli, thereby playing a critical role in bacterial pathogenesis. However, understanding how bacterial transcriptional regulatory networks function during host-pathogen interaction is limited. Recent studies in group A Streptococcus (GAS suggested that the transcriptional regulator catabolite control protein A (CcpA influences many of the same genes as the control of virulence (CovRS two-component gene regulatory system. To provide new information about the CcpA and CovRS networks, we compared the CcpA and CovR transcriptomes in a serotype M1 GAS strain. The transcript levels of several of the same genes encoding virulence factors and proteins involved in basic metabolic processes were affected in both DeltaccpA and DeltacovR isogenic mutant strains. Recombinant CcpA and CovR bound with high-affinity to the promoter regions of several co-regulated genes, including those encoding proteins involved in carbohydrate and amino acid metabolism. Compared to the wild-type parental strain, DeltaccpA and DeltacovRDeltaccpA isogenic mutant strains were significantly less virulent in a mouse myositis model. Inactivation of CcpA and CovR alone and in combination led to significant alterations in the transcript levels of several key GAS virulence factor encoding genes during infection. Importantly, the transcript level alterations in the DeltaccpA and DeltacovRDeltaccpA isogenic mutant strains observed during infection were distinct from those occurring during growth in laboratory medium. These data provide new knowledge regarding the molecular mechanisms by which pathogenic bacteria respond to environmental signals to regulate virulence factor production and basic metabolic processes during infection.

  4. Some viral and bacterial respiratory tract infections of dairy cattle during the summer season

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    Kale M.

    2013-01-01

    Full Text Available In this research, dairy cattle with respiratory system problems that were brought to a private slaughterhouse in Burdur province were investigated for viral and bacterial infections present in the summer season. The blood samples were collected from 56 animals. The samples were tested for antibodies against bovine herpesvirus 1 (BoHV-1, bovine viral diarrhea virus (BVDV, bovine respiratory syncytial virus (BRSV, bovine parainfluenza virus 3 (BPIV-3 and bovine adenovirus 3 (BAV-3 by ELISA. Bacteriological cultivation was carried out from lung samples taken after cutting the same animals. The seropositivity rates which were determined for 5 viruses in cattle (BoHV- 1, BVDV, BRSV, BPIV-3 and BAV-3 were 7.14%, 50%, 94.64%, 94.64% and 82.14% respectively. The presence of antibodies against the viruses was as follows; 5.36% of cattle had antibodies against only one virus, 14.29% against two, 30.36% against three, 44.64% against four and 5.36% against five viruses. A total of 36 bacterial agents were isolated from 30 out of 56 lung samples. From the lung samples, only one bacterium was isolated from 39.3% (22/56 samples, and more than one bacterium from 14.3% (8/56. Escherichia coli, Staphylococcus aureus and Streptococcus spp. were detected as the most often isolated agents. Compared to bacteria, the rates of viral infections associated with Escherichia coli (BRSV+BPIV-3+BAV- 3+Escherichia coli; 8.92% and BRSV+BPIV-3+Escherichia coli; 5.35% were higher. As a consequence, it was thought that primary agents which were the viruses and bacteria may have attended as secondary factors in respiratory tract infections of dairy cattle.

  5. Evaluating clinical periodontal measures as surrogates for bacterial exposure: The Oral Infections and Vascular Disease Epidemiology Study (INVEST)

    OpenAIRE

    Jacobs David R; Papapanou Panos N; Demmer Ryan T; Desvarieux Moïse

    2010-01-01

    Abstract Background Epidemiologic studies of periodontal infection as a risk factor for cardiovascular disease often use clinical periodontal measures as a surrogate for the underlying bacterial exposure of interest. There are currently no methodological studies evaluating which clinical periodontal measures best reflect the levels of subgingival bacterial colonization in population-based settings. We investigated the characteristics of clinical periodontal definitions that were most represen...

  6. Effect of long-term voluntary exercise wheel running on susceptibility to bacterial pulmonary infections in a mouse model

    DEFF Research Database (Denmark)

    van de Weert-van Leeuwen, Pauline B; de Vrankrijker, Angélica M M; Fentz, Joachim

    2013-01-01

    moderate exercise has many health benefits, healthy mice showed increased bacterial (P. aeruginosa) load and symptoms, after regular voluntary exercise, with perseverance of the phagocytic capacity of monocytes and neutrophils. Whether patients, suffering from bacterial infectious diseases, should......Regular moderate exercise has been suggested to exert anti-inflammatory effects and improve immune effector functions, resulting in reduced disease incidence and viral infection susceptibility. Whether regular exercise also affects bacterial infection susceptibility is unknown. The aim...... of this study was to investigate whether regular voluntary exercise wheel running prior to a pulmonary infection with bacteria (P. aeruginosa) affects lung bacteriology, sickness severity and phagocyte immune function in mice. Balb/c mice were randomly placed in a cage with or without a running wheel. After 28...

  7. A novel role of cannabinoids: implication in the fever induced by bacterial lipopolysaccharide.

    Science.gov (United States)

    Benamar, Khalid; Yondorf, Menachem; Meissler, Joseph J; Geller, Ellen B; Tallarida, Ronald J; Eisenstein, Toby K; Adler, Martin W

    2007-03-01

    There is continuing interest in elucidating the actions of drugs of abuse on the immune system and on infection. The present study investigated the effects of the cannabinoid (CB) receptor agonist aminoalkylindole, (+)-WIN 55,212-2 [(4,5-dihydro-2-methyl-4(4-morpholinylmethyl)-1-(1-naphthalenyl-carbonyl)-6H-pyrrolo[3,2,1ij]quinolin-6-one], on fever produced after injection of lipopolysaccharide (LPS), a component of the outer membrane of Gram-negative bacteria, the best known and most frequently used experimental model. Intraperitoneal injection of LPS (50 mug/kg) induced a biphasic fever, with the first peak at 180 min and the second at 300 min postinjection. Pretreatment with a nonhypothermic dose of the cannabinoid receptor agonist WIN 55,212-2 (0.5-1.5 mg/kg i.p.) antagonized the LPS-induced fever. However, pretreatment with the inactive enantiomer WIN 55,212-3 [1.5 mg/kg i.p.; S-(-)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthanlenyl)methanone mesylate] did not. The inhibitory effect of WIN 55,212-2 on LPS-induced fever was reversed by SR141716 [N-(piperdin-1-yl)-5-(4-chloropheny)-1-(2,4-dichloropheny)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride], a selective CB1 receptor antagonist, but not by SR144528 (N-[(1S)-endo-1,3,3-trimethylbicyclo[2.2.1]heptan-2-yl]5-(4-choro-3-methylphenyl)-1-(4-methylbenzyl)pyrazole-3-carboxamide), a selective antagonist at the CB2 receptor. The present results show that cannabinoids interact with systemic bacterial LPS injection and indicate a role of the CB1 receptor subtype in the pathogenesis of LPS fever.

  8. Mechanisms of ion-bombardment-induced DNA transfer into bacterial E. coli cells

    Energy Technology Data Exchange (ETDEWEB)

    Yu, L.D., E-mail: yuld@thep-center.org [Thailand Center of Excellence in Physics, Commission on Higher Education, 328 Si Ayutthaya Road, Bangkok 10400 (Thailand); Plasma and Beam Physics Research Facility, Department of Physics and Materials Science, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Sangwijit, K. [Molecular Biology Laboratory, Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Prakrajang, K. [Plasma and Beam Physics Research Facility, Department of Physics and Materials Science, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Faculty of Science, Maejo University, Chiang Mai 50290 (Thailand); Phanchaisri, B. [Institute of Science and Technology Research, Chiang Mai University, Chiang Mai 50200 (Thailand); Thongkumkoon, P. [Thailand Center of Excellence in Physics, Commission on Higher Education, 328 Si Ayutthaya Road, Bangkok 10400 (Thailand); Plasma and Beam Physics Research Facility, Department of Physics and Materials Science, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Thopan, P. [Plasma and Beam Physics Research Facility, Department of Physics and Materials Science, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Singkarat, S. [Thailand Center of Excellence in Physics, Commission on Higher Education, 328 Si Ayutthaya Road, Bangkok 10400 (Thailand); Plasma and Beam Physics Research Facility, Department of Physics and Materials Science, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand); Anuntalabhochai, S. [Molecular Biology Laboratory, Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai 50200 (Thailand)

    2014-05-01

    Highlights: • Ion bombardment could induce DNA transfer into E. coli cells. • The DNA transfer induction depended on ion energy and fluence. • The mechanism was associated with the bacterial cell envelope structure. • A mechanism phase diagram was proposed to summarize the mechanism. - Abstract: As a useful ion beam biotechnology, ion-bombardment-induced DNA transfer into bacterial Escherichia coli (E. coli) cells has been successfully operated using argon ions. In the process ion bombardment of the bacterial cells modifies the cell envelope materials to favor the exogenous DNA molecules to pass through the envelope to enter the cell. The occurrence of the DNA transfer induction was found ion energy and fluence dependent in a complex manner. At ion energy of a few keV and a few tens of keV to moderate fluences the DNA transfer could be induced by ion bombardment of the bacterial cells, while at the same ion energy but to high fluences DNA transfer could not be induced. On the other hand, when the ion energy was medium, about 10–20 keV, the DNA transfer could not be induced by ion bombardment of the cells. The complexity of the experimental results indicated a complex mechanism which should be related to the complex structure of the bacterial E. coli cell envelope. A phase diagram was proposed to interpret different mechanisms involved as functions of the ion energy and fluence.

  9. Chlamydia induces anchorage independence in 3T3 cells and detrimental cytological defects in an infection model.

    Directory of Open Access Journals (Sweden)

    Andrea E Knowlton

    Full Text Available Chlamydia are gram negative, obligate intracellular bacterial organisms with different species causing a multitude of infections in both humans and animals. Chlamydia trachomatis is the causative agent of the sexually transmitted infection (STI Chlamydia, the most commonly acquired bacterial STI in the United States. Chlamydial infections have also been epidemiologically linked to cervical cancer in women co-infected with the human papillomavirus (HPV. We have previously shown chlamydial infection results in centrosome amplification and multipolar spindle formation leading to chromosomal instability. Many studies indicate that centrosome abnormalities, spindle defects, and chromosome segregation errors can lead to cell transformation. We hypothesize that the presence of these defects within infected dividing cells identifies a possible mechanism for Chlamydia as a cofactor in cervical cancer formation. Here we demonstrate that infection with Chlamydia trachomatis is able to transform 3T3 cells in soft agar resulting in anchorage independence and increased colony formation. Additionally, we show for the first time Chlamydia infects actively replicating cells in vivo. Infection of mice with Chlamydia results in significantly increased cell proliferation within the cervix, and in evidence of cervical dysplasia. Confocal examination of these infected tissues also revealed elements of chlamydial induced chromosome instability. These results contribute to a growing body of data implicating a role for Chlamydia in cervical cancer development and suggest a possible molecular mechanism for this effect.

  10. Bacterial virulence phenotypes of Escherichia coli and host susceptibility determine risk for urinary tract infections.

    Science.gov (United States)

    Schreiber, Henry L; Conover, Matt S; Chou, Wen-Chi; Hibbing, Michael E; Manson, Abigail L; Dodson, Karen W; Hannan, Thomas J; Roberts, Pacita L; Stapleton, Ann E; Hooton, Thomas M; Livny, Jonathan; Earl, Ashlee M; Hultgren, Scott J

    2017-03-22

    Urinary tract infections (UTIs) are caused by uropathogenic Escherichia coli (UPEC) strains. In contrast to many enteric E. coli pathogroups, no genetic signature has been identified for UPEC strains. We conducted a high-resolution comparative genomic study using E. coli isolates collected from the urine of women suffering from frequent recurrent UTIs. These isolates were genetically diverse and varied in their urovirulence, that is, their ability to infect the bladder in a mouse model of cystitis. We found no set of genes, including previously defined putative urovirulence factors (PUFs), that were predictive of urovirulence. In addition, in some patients, the E. coli strain causing a recurrent UTI had fewer PUFs than the supplanted strain. In competitive experimental infections in mice, the supplanting strain was more efficient at colonizing the mouse bladder than the supplanted strain. Despite the lack of a clear genomic signature for urovirulence, comparative transcriptomic and phenotypic analyses revealed that the expression of key conserved functions during culture, such as motility and metabolism, could be used to predict subsequent colonization of the mouse bladder. Together, our findings suggest that UTI risk and outcome may be determined by complex interactions between host susceptibility and the urovirulence potential of diverse bacterial strains.

  11. Fecal Bacterial Communities in treated HIV infected individuals on two antiretroviral regimens

    Science.gov (United States)

    Pinto-Cardoso, Sandra; Lozupone, Catherine; Briceño, Olivia; Alva-Hernández, Selma; Téllez, Norma; Adriana, Aguilar; Murakami-Ogasawara, Akio; Reyes-Terán, Gustavo

    2017-01-01

    Intestinal microbiome changes that occur in HIV positive individuals on different antiretroviral therapy (ART) regimens are important to understand, as they are potentially linked with chronic inflammation and microbiome-linked comorbidities that occur at increased incidence in this population. We conducted a cross-sectional study comparing the fecal microbiomes of HIV-uninfected (HIV SN) to HIV-infected individuals on long-term ART (HIV+ LTART) from Mexico using 16S ribosomal RNA (16sRNA) targeted sequencing. These individuals were on two ART regimens based on either Non-Nucleoside Reverse Transcriptase Inhibitors (EFV) or ritonavir-boosted Protease Inhibitors (PI) with the same backbone of Nucleoside Reverse Transcriptase Inhibitors. Microbiome diversity was reduced in treated HIV infection compared to HIV SN (p < 0.05). Several operational taxonomic units (OTUs) related to the Ruminococcaceae family including Faecalibacterium prausnitzii were depleted in EFV and PI compared to HIV SN and negatively correlated with intestinal gut dysfunction as measured by the intestinal fatty binding protein (p < 0.05). This is the first report to address the fecal bacterial communities in HIV-infected individuals on two ARV regimens from Mexico. PMID:28262770

  12. The bacterial pathogen Xylella fastidiosa affects the leaf ionome of plant hosts during infection.

    Directory of Open Access Journals (Sweden)

    Leonardo De La Fuente

    Full Text Available Xylella fastidiosa is a plant pathogenic bacterium that lives inside the host xylem vessels, where it forms biofilm believed to be responsible for disrupting the passage of water and nutrients. Here, Nicotiana tabacum was infected with X. fastidiosa, and the spatial and temporal changes in the whole-leaf ionome (i.e. the mineral and trace element composition were measured as the host plant transitioned from healthy to diseased physiological status. The elemental composition of leaves was used as an indicator of the physiological changes in the host at a specific time and relative position during plant development. Bacterial infection was found to cause significant increases in concentrations of calcium prior to the appearance of symptoms and decreases in concentrations of phosphorous after symptoms appeared. Field-collected leaves from multiple varieties of grape, blueberry, and pecan plants grown in different locations over a four-year period in the Southeastern US showed the same alterations in Ca and P. This descriptive ionomics approach characterizes the existence of a mineral element-based response to X. fastidiosa using a model system suitable for further manipulation to uncover additional details of the role of mineral elements during plant-pathogen interactions. This is the first report on the dynamics of changes in the ionome of the host plant throughout the process of infection by a pathogen.

  13. Pentosan polysulfate protects brain endothelial cells against bacterial lipopolysaccharide-induced damages.

    Science.gov (United States)

    Veszelka, Szilvia; Pásztói, Mária; Farkas, Attila E; Krizbai, István; Ngo, Thi Khue Dung; Niwa, Masami; Abrahám, Csongor S; Deli, Mária A

    2007-01-01

    Peripheral inflammation can aggravate local brain inflammation and neuronal death. The blood-brain barrier (BBB) is a key player in the event. On a relevant in vitro model of primary rat brain endothelial cells co-cultured with primary rat astroglia cells lipopolysaccharide (LPS)-induced changes in several BBB functions have been investigated. LPS-treatment resulted in a dose- and time-dependent decrease in the integrity of endothelial monolayers: transendothelial electrical resistance dropped, while flux of permeability markers fluorescein and albumin significantly increased. Immunostaining for junctional proteins ZO-1, claudin-5 and beta-catenin was significantly weaker in LPS-treated endothelial cells than in control monolayers. LPS also reduced the intensity and changed the pattern of ZO-1 immunostaining in freshly isolated rat brain microvessels. The activity of P-glycoprotein, an important efflux pump at the BBB, was also inhibited by LPS. At the same time production of reactive oxygen species and nitric oxide was increased in brain endothelial cells treated with LPS. Pentosan polysulfate, a polyanionic polysaccharide could reduce the deleterious effects of LPS on BBB permeability, and P-glycoprotein activity. LPS-stimulated increase in the production of reactive oxygen species and nitric oxide was also decreased by pentosan treatment. The protective effect of pentosan for brain endothelium can be of therapeutical significance in bacterial infections affecting the BBB.

  14. Brucella abortus-infected B cells induce osteoclastogenesis.

    Science.gov (United States)

    Pesce Viglietti, Ayelén Ivana; Arriola Benitez, Paula Constanza; Giambartolomei, Guillermo Hernán; Delpino, María Victoria

    2016-09-01

    Brucella abortus is an intracellular bacterium that establishes lifelong infections in livestock and humans although the mechanisms of its chronicity are poorly understood. Activated B cells have long lifespan and B. abortus infection activates B cells. Our results indicate that the direct infection of B cells with B. abortus induced matrix metalloproteinase-9 (MMP-9), receptor activator for NF κB ligand (RANKL), tumor necrosis factor (TNF)-α and interleukin (IL)-6 secretion. In addition, supernatants from B. abortus-infected B cells induced bone marrow-derived monocytes to undergo osteoclastogenesis. Using osteoprotegerin, RANKL's decoy receptor, we determined that RANKL is involved in osteoclastogenesis induced by supernatants from B. abortus-infected B cells. The results presented here shed light on how the interactions of B. abortus with B cells may have a role in the pathogenesis of brucellar osteoarticular disease.

  15. Influenza virus induces bacterial and nonbacterial otitis media.

    NARCIS (Netherlands)

    Short, K.R.; Diavatopoulos, D.A.; Thornton, R.; Pedersen, J.; Strugnell, R.A.; Wise, A.K.; Reading, P.C.; Wijburg, O.L.

    2011-01-01

    Otitis media (OM) is one of the most common childhood diseases. OM can arise when a viral infection enables bacteria to disseminate from the nasopharynx to the middle ear. Here, we provide the first infant murine model for disease. Mice coinfected with Streptococcus pneumoniae and influenza virus ha

  16. Fosfomycin i.v. for Treatment of Severely Infected Patients

    Science.gov (United States)

    2017-02-28

    Bacterial Infections; Bone Diseases, Infectious; Osteomyelitis; Central Nervous System Bacterial Infections; Meningitis, Bacterial; Encephalitis; Brain Abscess; Urinary Tract Infections; Respiratory Tract Infections; Pneumonia, Bacterial; Skin Diseases, Bacterial; Soft Tissue Infections; Intraabdominal Infections; Sepsis; Bacteremia; Endocarditis, Bacterial

  17. Copper Is a Host Effector Mobilized to Urine during Urinary Tract Infection To Impair Bacterial Colonization.

    Science.gov (United States)

    Hyre, Amanda N; Kavanagh, Kylie; Kock, Nancy D; Donati, George L; Subashchandrabose, Sargurunathan

    2017-03-01

    Urinary tract infection (UTI) is a major global infectious disease affecting millions of people annually. Human urinary copper (Cu) content is elevated during UTI caused by uropathogenic Escherichia coli (UPEC). UPEC upregulates the expression of Cu efflux genes during clinical UTI in patients as an adaptive response to host-derived Cu. Whether Cu is mobilized to urine as a host response to UTI and its role in protection against UTI remain unresolved. To address these questions, we tested the hypothesis that Cu is a host effector mobilized to urine during UTI to limit bacterial growth. Our results reveal that Cu is mobilized to urine during UTI caused by the major uropathogens Proteus mirabilis and Klebsiella pneumoniae, in addition to UPEC, in humans. Ceruloplasmin, a Cu-containing ferroxidase, is found at higher levels in UTI urine than in healthy control urine and serves as the molecular source of urinary Cu during UTI. Our results demonstrate that ceruloplasmin decreases the bioavailability of iron in urine by a transferrin-dependent mechanism. Experimental UTI with UPEC in nonhuman primates recapitulates the increased urinary Cu content observed during clinical UTI. Furthermore, Cu-deficient mice are highly colonized by UPEC, indicating that Cu is involved in the limiting of bacterial growth within the urinary tract. Collectively, our results indicate that Cu is a host effector that is involved in protection against pathogen colonization of the urinary tract. Because urinary Cu levels are amenable to modulation, augmentation of the Cu-based host defense against UTI represents a novel approach to limiting bacterial colonization during UTI.

  18. Microbiota and the gut-liver axis: bacterial translocation, inflammation and infection in cirrhosis.

    Science.gov (United States)

    Giannelli, Valerio; Di Gregorio, Vincenza; Iebba, Valerio; Giusto, Michela; Schippa, Serena; Merli, Manuela; Thalheimer, Ulrich

    2014-12-07

    Liver disease is associated with qualitative and quantitative changes in the intestinal microbiota. In cirrhotic patients the alteration in gut microbiota is characterized by an overgrowth of potentially pathogenic bacteria (i.e., gram negative species) and a decrease in autochthonous familiae. Here we summarize the available literature on the risk of gut dysbiosis in liver cirrhosis and its clinical consequences. We therefore described the features of the complex interaction between gut microbiota and cirrhotic host, the so called "gut-liver axis", with a particular attention to the acquired risk of bacterial translocation, systemic inflammation and the relationship with systemic infections in the cirrhotic patient. Such knowledge might help to develop novel and innovative strategies for the prevention and therapy of gut dysbiosis and its complication in liver cirrhosis.

  19. Hyperbranched poly(NIPAM) polymers modified with antibiotics for the reduction of bacterial burden in infected human tissue engineered skin.

    Science.gov (United States)

    Shepherd, Joanna; Sarker, Prodip; Rimmer, Stephen; Swanson, Linda; MacNeil, Sheila; Douglas, Ian

    2011-01-01

    The escalating global incidence of bacterial infection, particularly in chronic wounds, is a problem that requires significant improvements to existing therapies. We have developed hyperbranched poly(NIPAM) polymers functionalized with the antibiotics Vancomycin and Polymyxin-B that are sensitive to the presence of bacteria in solution. Binding of bacteria to the polymers causes a conformational change, resulting in collapse of the polymers and the formation of insoluble polymer/bacteria complexes. We have applied these novel polymers to our tissue engineered human skin model of a burn wound infected with Pseudomonas aeruginosa and Staphylococcus aureus. When the polymers were removed from the infected skin, either in a polymer gel solution or in the form of hydrogel membranes, they removed bound bacteria, thus reducing the bacterial load in the infected skin model. These bacteria-binding polymers have many potential uses, including coatings for wound dressings.

  20. Reptiles as Reservoirs of Bacterial Infections: Real Threat or Methodological Bias?

    Science.gov (United States)

    Zancolli, Giulia; Mahsberg, Dieter; Sickel, Wiebke; Keller, Alexander

    2015-10-01

    Bacterial infections secondary to snakebites and human pathogens (e.g., Salmonella) have been linked to the oral microbiota of snakes and pet reptiles. Based on culture-dependent studies, it is speculated that snakes' oral microbiota reflects the fecal flora of their ingested preys. However, cultured-based techniques have been shown to be limited as they fail to identify unculturable microorganisms which represent the vast majority of the microbial diversity. Here, we used culture-independent high-throughput sequencing to identify reptile-associated pathogens and to characterize the oral microbial community of five snakes, one gecko, and two terrapins. Few potential human pathogens were detected at extremely low frequencies. Moreover, bacterial taxa represented in the snake's oral cavity bore little resemblance to their preys' fecal microbiota. Overall, we found distinct, highly diverse microbial communities with consistent, species-specific patterns contrary to previous culture-based studies. Our study does not support the widely held assumption that reptiles' oral cavity acts as pathogen reservoir and provides important insights for future research.

  1. Serum sialic acid in malignant tumors, bacterial infections, and chronic liver diseases.

    Science.gov (United States)

    Stefenelli, N; Klotz, H; Engel, A; Bauer, P

    1985-01-01

    The total serum sialic acid concentration was determined in 2,264 persons with various malignant tumors, bacterial infections, rheumatic diseases, and chronic liver diseases, and in a control group. The thiobarbiturate method according to Warren was used. The upper limit (95% percentile) in the control group was 2.23 mumol/ml. Higher values were found in the groups with neoplasms (mean: 3.04 mumol/ml), inflammatory diseases (e.g., pneumonia: 3.02 mumol/ml), and active rheumatoid arthritis (3.05 mumol/ml). In the group with malignant diseases, the sialic acid concentration at the time of diagnosis was highest for bronchial carcinoma (3.29 mumol/ml) and lowest for breast cancer (2.58 mumol/ml). In chronic liver diseases the mean sialic acid level was lower than in a heterogeneous group of noninflammatory and nonneoplastic diseases. The estimation of the serum sialic acid concentration could be useful in the detection of tumor burden and metastases, and in the evaluation of the later course and prognosis of malignant neoplasms if bacterial/inflammatory and active rheumatoid processes can be excluded.

  2. Bacterial isolates from burn wound infections and their antibiograms: A eight-year study

    Directory of Open Access Journals (Sweden)

    Mehta Manjula

    2007-01-01

    Full Text Available Background: Infection is an important cause of mortality in burns. Rapidly emerging nosocomial pathogens and the problem of multi-drug resistance necessitates periodic review of isolation patterns and antibiogram in the burn ward. Aim: Keeping this in mind, the present retrospective study from wounds of patients admitted to burns unit was undertaken to determine the bacteriological profile and the resistance pattern from the burn ward over a period of three years (June 2002 to May 2005 and was compared with the results obtained during the previous five years (June 1997-May 2002, to ascertain any change in the bacteriological profile and antimicrobial resistance pattern. Materials and Methods: Bacterial isolates from 268 wound swabs taken from burn patients were identified by conventional biochemical methods and antimicrobial susceptibility was performed. Statistical comparison of bacterial isolates and their resistance pattern with previous five years data was done using c2 test. Results and Conclusions: During the period from 2002 to 2005 Pseudomonas species was the commonest pathogen isolated (51.5% followed by Acinetobacter species (14.28%, Staph. aureus (11.15%, Klebsiella species (9.23% and Proteus species (2.3%. When compared with the results of the previous five years i.e., 1997 to 2002, Pseudomonas species was still the commonest pathogen in the burns unit. However, the isolation of this organism and other gram-negative organisms had decreased in comparison to previous years. Newer drugs were found to be effective.

  3. Bacteriophages: an appraisal of their role in the treatment of bacterial infections.

    Science.gov (United States)

    Hanlon, Geoffrey William

    2007-08-01

    Bacteriophages were first used successfully to treat bacterial infections a decade before penicillin was discovered. However, the excitement that greeted those initial successes was short-lived, as a lack of understanding of basic phage biology subsequently led to a catalogue of clinical failures. As a consequence, bacteriophage therapy was largely abandoned in the West in favour of the newly emerging antibiotics. Now, as the problem of antibiotic resistance becomes ever more acute, a number of scientists and clinicians are looking again at bacteriophages as a therapeutic option in the treatment of bacterial infections. The chances of success second time round would appear to be much better given our current extensive knowledge of bacteriophage biology following their important role in underpinning the advances in molecular biology. We also have available to us the experience of nearly 80 years of clinical usage in the countries of the former Soviet Union and Eastern Europe as well as a political climate that encourages sharing of that knowledge. This review outlines those features of bacteriophages that contribute to their utility in therapy and explores the potential for their re-introduction into Western medicine. An abundance of clinical evidence is available in the Soviet literature but much of this is technically flawed and a more realistic appraisal of the clinical value of phages can be obtained from animal studies conducted in the West. As interest in bacteriophages increases, a number of companies throughout the world have begun investing in phage technology and this has led to novel approaches to therapy, some of which will be discussed.

  4. Lysis-deficient phages as novel therapeutic agents for controlling bacterial infection

    Directory of Open Access Journals (Sweden)

    Kempashanaiah Nanjundappa

    2011-08-01

    Full Text Available Abstract Background Interest in phage therapy has grown over the past decade due to the rapid emergence of antibiotic resistance in bacterial pathogens. However, the use of bacteriophages for therapeutic purposes has raised concerns over the potential for immune response, rapid toxin release by the lytic action of phages, and difficulty in dose determination in clinical situations. A phage that kills the target cell but is incapable of host cell lysis would alleviate these concerns without compromising efficacy. Results We developed a recombinant lysis-deficient Staphylococcus aureus phage P954, in which the endolysin gene was rendered nonfunctional by insertional inactivation. P954, a temperate phage, was lysogenized in S. aureus strain RN4220. The native endolysin gene on the prophage was replaced with an endolysin gene disrupted by the chloramphenicol acetyl transferase (cat gene through homologous recombination using a plasmid construct. Lysogens carrying the recombinant phage were detected by growth in presence of chloramphenicol. Induction of the recombinant prophage did not result in host cell lysis, and the phage progeny were released by cell lysis with glass beads. The recombinant phage retained the endolysin-deficient genotype and formed plaques only when endolysin was supplemented. The host range of the recombinant phage was the same as that of the parent phage. To test the in vivo efficacy of the recombinant endolysin-deficient phage, immunocompromised mice were challenged with pathogenic S. aureus at a dose that results in 80% mortality (LD80. Treatment with the endolysin-deficient phage rescued mice from the fatal S. aureus infection. Conclusions A recombinant endolysin-deficient staphylococcal phage has been developed that is lethal to methicillin-resistant S. aureus without causing bacterial cell lysis. The phage was able to multiply in lytic mode utilizing a heterologous endolysin expressed from a plasmid in the propagation host

  5. Host and bacterial proteins that repress recruitment of LC3 to Shigella early during infection.

    Directory of Open Access Journals (Sweden)

    Leigh A Baxt

    Full Text Available Shigella spp. are intracytosolic gram-negative pathogens that cause disease by invasion and spread through the colonic mucosa, utilizing host cytoskeletal components to form propulsive actin tails. We have previously identified the host factor Toca-1 as being recruited to intracellular S. flexneri and being required for efficient bacterial actin tail formation. We show that at early times during infection (40 min., the type three-secreted effector protein IcsB recruits Toca-1 to intracellular bacteria and that recruitment of Toca-1 is associated with repression of recruitment of LC3, as well as with repression of recruitment of the autophagy marker NDP52, around these intracellular bacteria. LC3 is best characterized as a marker of autophagosomes, but also marks phagosomal membranes in the process LC3-associated phagocytosis. IcsB has previously been demonstrated to be required for S. flexneri evasion of autophagy at late times during infection (4-6 hr by inhibiting binding of the autophagy protein Atg5 to the Shigella surface protein IcsA (VirG. Our results suggest that IcsB and Toca-1 modulation of LC3 recruitment restricts LC3-associated phagocytosis and/or LC3 recruitment to vacuolar membrane remnants. Together with published results, our findings suggest that IcsB inhibits innate immune responses in two distinct ways, first, by inhibiting LC3-associated phagocytosis and/or LC3 recruitment to vacuolar membrane remnants early during infection, and second, by inhibiting autophagy late during infection.

  6. Bacterial, Fungal, and Parasitic Infections of the Central Nervous System: Radiologic-Pathologic Correlation and Historical Perspectives.

    Science.gov (United States)

    Shih, Robert Y; Koeller, Kelly K

    2015-01-01

    Despite remarkable progress in prevention and treatment, infectious diseases affecting the central nervous system remain an important source of morbidity and mortality, particularly in less-developed countries and in immunocompromised persons. Bacterial, fungal, and parasitic pathogens are derived from living organisms and affect the brain, spinal cord, or meninges. Infections due to these pathogens are associated with a variety of neuroimaging patterns that can be appreciated at magnetic resonance imaging in most cases. Bacterial infections, most often due to Streptococcus, Haemophilus, and Neisseria species, cause significant meningitis, whereas the less common cerebritis and subsequent abscess formation have well-documented progression, with increasingly prominent altered signal intensity and corresponding contrast enhancement. Atypical bacterial infections are characterized by the development of a granulomatous response, classically seen in tuberculosis, in which the tuberculoma is the most common parenchymal form of the disease; spirochetal and rickettsial diseases are less common. Fungal infections predominate in immunocompromised hosts and are caused by yeasts, molds, and dimorphic fungi. Cryptococcal meningitis is the most common fungal infection, whereas candidiasis is the most common nosocomial infection. Mucormycosis and aspergillosis are characterized by angioinvasiveness and are associated with high morbidity and mortality among immunocompromised patients. In terms of potential exposure in the worldwide population, parasitic infections, including neurocysticercosis, toxoplasmosis, echinococcosis, malaria, and schistosomiasis, are the greatest threat. Rare amebic infections are noteworthy for their extreme virulence and high mortality. The objective of this article is to highlight the characteristic neuroimaging manifestations of bacterial, fungal, and parasitic diseases, with emphasis on radiologic-pathologic correlation and historical perspectives.

  7. Quieting cross talk-the quorum sensing regulator LsrR as a possible target for fighting bacterial infections

    Institute of Scientific and Technical Information of China (English)

    Christopher M Byrd; William E Bentley

    2009-01-01

    @@ Antibiotic-resistant bacteria continue to emerge at alarming rates and all aspects of the infection process are being re-examined so that new procedures for prevention,diagnosis,and treatment of bacterial infections can be developed that reduce their occurrence and severity as well as the economic impact on health care systems.One of the most problematic pathogens is methicillin-resistant Staphylococcus aureus(MRSA).

  8. Are bacterial volatile compounds poisonous odors to a fungal pathogen Botrytis cinerea, alarm signals to Arabidopsis seedlings for eliciting induced resistance, or both?

    Directory of Open Access Journals (Sweden)

    Choong-Min eRyu

    2016-02-01

    Full Text Available Biological control (biocontrol agents act on plants via numerous mechanisms, and can be used to protect plants from pathogens. Biocontrol agents can act directly as pathogen antagonists or competitors or indirectly to promote plant induced systemic resistance (ISR. Whether a biocontrol agent acts directly or indirectly depends on the specific strain and the pathosystem type. We reported previously that bacterial volatile organic compounds (VOCs are determinants for eliciting plant ISR. Emerging data suggest that bacterial VOCs also can directly inhibit fungal and plant growth. The aim of the current study was to differentiate direct and indirect mechanisms of bacterial VOC effects against Botrytis cinerea infection of Arabidopsis. Volatile emissions from Bacillus subtilis GB03 successfully protected Arabidopsis seedlings against B. cinerea. First, we investigated the direct effects of bacterial VOCs on symptom development and different phenological stages of B. cinerea including spore germination, mycelial attachment to the leaf surface, mycelial growth, and sporulation in vitro and in planta. Volatile emissions inhibited hyphal growth in a dose-dependent manner in vitro, and interfered with fungal attachment on the hydrophobic leaf surface. Second, the optimized bacterial concentration that did not directly inhibit fungal growth successfully protected Arabidopsis from fungal infection, which indicates that bacterial VOC-elicited plant ISR has a more important role in biocontrol than direct inhibition of fungal growth on Arabidopsis. We performed qRT-PCR to investigate the priming of the defense-related genes PR1, PDF1.2, and ChiB at 0, 12, 24, and 36 hours post-infection and 14 days after the start of plant exposure to bacterial VOCs. The results indicate that bacterial VOCs potentiate expression of PR1 and PDF1.2 but not ChiB, which stimulates SA- and JA-dependent signaling pathways in plant ISR and protects plants against pathogen

  9. Polymicrobial infection with major periodontal pathogens induced periodontal disease and aortic atherosclerosis in hyperlipidemic ApoE(null mice.

    Directory of Open Access Journals (Sweden)

    Mercedes F Rivera

    Full Text Available Periodontal disease (PD and atherosclerosis are both polymicrobial and multifactorial and although observational studies supported the association, the causative relationship between these two diseases is not yet established. Polymicrobial infection-induced periodontal disease is postulated to accelerate atherosclerotic plaque growth by enhancing atherosclerotic risk factors of orally infected Apolipoprotein E deficient (ApoE(null mice. At 16 weeks of infection, samples of blood, mandible, maxilla, aorta, heart, spleen, and liver were collected, analyzed for bacterial genomic DNA, immune response, inflammation, alveolar bone loss, serum inflammatory marker, atherosclerosis risk factors, and aortic atherosclerosis. PCR analysis of polymicrobial-infected (Porphyromonas gingivalis [P. gingivalis], Treponema denticola [T. denticola], and Tannerella forsythia [T. forsythia] mice resulted in detection of bacterial genomic DNA in oral plaque samples indicating colonization of the oral cavity by all three species. Fluorescent in situ hybridization detected P. gingivalis and T. denticola within gingival tissues of infected mice and morphometric analysis showed an increase in palatal alveolar bone loss (p<0.0001 and intrabony defects suggesting development of periodontal disease in this model. Polymicrobial-infected mice also showed an increase in aortic plaque area (p<0.05 with macrophage accumulation, enhanced serum amyloid A, and increased serum cholesterol and triglycerides. A systemic infection was indicated by the detection of bacterial genomic DNA in the aorta and liver of infected mice and elevated levels of bacterial specific IgG antibodies (p<0.0001. This study was a unique effort to understand the effects of a polymicrobial infection with P. gingivalis, T. denticola and T. forsythia on periodontal disease and associated atherosclerosis in ApoE(null mice.

  10. Bacterial characteristics of importance for recurrent urinary tract infections caused by Escherichia coli.

    Science.gov (United States)

    Ejrnæs, Karen

    2011-04-01

    Urinary tract infections (UTIs) are among the most common bacterial infectious diseases encountered in clinical practice and account for significant morbidity and high medical costs. Escherichia coli is the most predominant pathogen causing 80-90% of community-acquired UTIs and 30-50% of nosocomially-acquired UTIs. Recurrent UTIs (RUTIs) are reported in 25% of women within 6 months of an acute UTI episode and pose a major problem. The aim of the present thesis was to look for bacterial characteristics of importance for recurrence of UTI caused by E. coli. The thesis is based on three papers. The study is based on E. coli from 236 Swedish women with community-acquired symptomatic lower UTI from a large study of 1162 patients treated with one of three different dosing regimens of pivmecillinam or placebo. The women were evaluated clinically and bacteriologically at the initial visit and at two scheduled follow-up visits. According to pulsed-field gel electrophoresis (PFGE) and culture results all primary infecting E. coli (initial isolates, pretherapy) were assigned into whether the initial infection was followed by cure, persistence, reinfection or relapse during follow-up. The prevalence of virulence factor genes (VFGs), phylogenetic groups, biofilm formation, plasmids and resistance to antimicrobials among primary infecting E. coli causing persistence or relapse at the follow-up visits were compared with the prevalence of these among E. coli followed by cure or reinfection. Previous studies of RUTI using phenotypically based typing methods or less specific DNA based typing methods have concluded, that RUTIs are mainly attributable to reinfection with new strains. However, applying PFGE showed that 77% of RUTIs were caused by a relapse with the primary infecting E. coli (Paper I). This may support the recent observation that E. coli can invade and replicate within the murine bladder forming biofilm-like intracellular bacterial communities (IBCs) and establish

  11. Multi-species bacterial biofilm and intracellular infection in otitis media

    Directory of Open Access Journals (Sweden)

    Thornton Ruth B

    2011-10-01

    Full Text Available Abstract Background Bacteria which are metabolically active yet unable to be cultured and eradicated by antibiotic treatment are present in the middle ear effusion of children with chronic otitis media with effusion (COME and recurrent acute otitis media (rAOM. These observations are suggestive of biofilm presence or intracellular sequestration of bacteria and may play a role in OM pathogenesis. The aim of this project is to provide evidence for the presence of otopathogenic bacteria intracellularly or within biofilm in the middle ear mucosa of children with COME or rAOM. Methods Middle ear mucosal biopsies from 20 children with COME or rAOM were examined for otopathogenic bacteria (either in biofilm or located intracellularly using transmission electron microscopy (TEM or species specific fluorescent in situ hybridisation (FISH and confocal laser scanning microscopy (CLSM. One healthy control biopsy from a child undergoing cochlear implant surgery was also examined. Results No bacteria were observed in the healthy control sample. In 2 of the 3 biopsies imaged using TEM, bacteria were observed in mucus containing vacuoles within epithelial cells. Bacterial species within these could not be identified and biofilm was not observed. Using FISH with CLSM, bacteria were seen in 15 of the 17 otitis media mucosal specimens. In this group, 11 (65% of the 17 middle ear mucosal biopsies showed evidence of bacterial biofilm and 12 demonstrated intracellular bacteria. 52% of biopsies were positive for both biofilm and intracellular bacteria. At least one otopathogen was identified in 13 of the 15 samples where bacteria were present. No differences were observed between biopsies from children with COME and those with rAOM. Conclusion Using FISH and CLSM, bacterial biofilm and intracellular infection with known otopathogens are demonstrated on/in the middle ear mucosa of children with COME and/or rAOM. While their role in disease pathogenesis remains to be

  12. Anhydride-functional silane immobilized onto titanium surfaces induces osteoblast cell differentiation and reduces bacterial adhesion and biofilm formation

    Energy Technology Data Exchange (ETDEWEB)

    Godoy-Gallardo, Maria, E-mail: maria.godoy.gallardo@upc.edu [Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgy, Technical University of Catalonia (UPC), ETSEIB, Av. Diagonal 647, 08028 Barcelona (Spain); Centre for Research in NanoEngineering (CRNE) — UPC, C/ Pascual i Vila 15, 08028 Barcelona (Spain); Guillem-Marti, Jordi, E-mail: jordi.guillem.marti@upc.edu [Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgy, Technical University of Catalonia (UPC), ETSEIB, Av. Diagonal 647, 08028 Barcelona (Spain); Centre for Research in NanoEngineering (CRNE) — UPC, C/ Pascual i Vila 15, 08028 Barcelona (Spain); Sevilla, Pablo, E-mail: psevilla@euss.es [Department of Mechanics, Escola Universitària Salesiana de Sarrià (EUSS), C/ Passeig de Sant Bosco, 42, 08017 Barcelona (Spain); Manero, José M., E-mail: jose.maria.manero@upc.edu [Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgy, Technical University of Catalonia (UPC), ETSEIB, Av. Diagonal 647, 08028 Barcelona (Spain); Centre for Research in NanoEngineering (CRNE) — UPC, C/ Pascual i Vila 15, 08028 Barcelona (Spain); Gil, Francisco J., E-mail: francesc.xavier.gil@upc.edu [Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Metallurgy, Technical University of Catalonia (UPC), ETSEIB, Av. Diagonal 647, 08028 Barcelona (Spain); Centre for Research in NanoEngineering (CRNE) — UPC, C/ Pascual i Vila 15, 08028 Barcelona (Spain); and others

    2016-02-01

    Bacterial infection in dental implants along with osseointegration failure usually leads to loss of the device. Bioactive molecules with antibacterial properties can be attached to titanium surfaces with anchoring molecules such as silanes, preventing biofilm formation and improving osseointegration. Properties of silanes as molecular binders have been thoroughly studied, but research on the biological effects of these coatings is scarce. The aim of the present study was to determine the in vitro cell response and antibacterial effects of triethoxysilypropyl succinic anhydride (TESPSA) silane anchored on titanium surfaces. X-ray photoelectron spectroscopy confirmed a successful silanization. The silanized surfaces showed no cytotoxic effects. Gene expression analyses of Sarcoma Osteogenic (SaOS-2) osteoblast-like cells cultured on TESPSA silanized surfaces reported a remarkable increase of biochemical markers related to induction of osteoblastic cell differentiation. A manifest decrease of bacterial adhesion and biofilm formation at early stages was observed on treated substrates, while favoring cell adhesion and spreading in bacteria–cell co-cultures. Surfaces treated with TESPSA could enhance a biological sealing on implant surfaces against bacteria colonization of underlying tissues. Furthermore, it can be an effective anchoring platform of biomolecules on titanium surfaces with improved osteoblastic differentiation and antibacterial properties. - Highlights: • TESPSA silane induces osteoblast differentiation. • TESPSA reduces bacterial adhesion and biofilm formation. • TESPSA is a promising anchoring platform of biomolecules onto titanium.

  13. Screening Helicobacter pylori genes induced during infection of mouse stomachs

    Institute of Scientific and Technical Information of China (English)

    Aparna Singh; Nathaniel Hodgson; Ming Yan; Jungsoo Joo; Lei Gu; Hong Sang; Emmalena Gregory-Bryson

    2012-01-01

    AIM:To investigate the effect of in vivo environment on gene expression in Helicobacter pylori (H.pylori) as it relates to its survival in the host.METHODS:In vivo expression technology (IVET) systems are used to identify microbial virulence genes.We modified the IVET-transcriptional fusion vector,pIVET8,which uses antibiotic resistance as the basis for selection of candidate genes in host tissues to develop two unique IVET-promoter-screening vectors,pIVET11 and pIVET12.Our novel IVET systems were developed by the fusion of random Sau3A DNA fragments of H.pylori and a tandem-reporter system of chloramphenicol acetyltransferase and beta-galactosidase.Additionally,each vector contains a kanamycin resistance gene.We used a mouse macrophage cell line,RAW 264.7 and mice,as selective media to identify specific genes that H.pylori expresses in vivo.Gene expression studies were conducted by infecting RAW 264.7 cells with H.pylori.This was followed by real time polymerase chain reaction (PCR) analysis to determine the relative expression levels of in vivo induced genes.RESULTS:In this study,we have identified 31 in vivo induced (ivi) genes in the initial screens.These 31 genes belong to several functional gene families,including several well-known virulence factors that are expressed by the bacterium in infected mouse stomachs.Virulence factors,vacA and cagA,were found in this screen and are known to play important roles in H.pylori infection,colonization and pathogenesis.Their detection validates the efficacy of these screening systems.Some of the identified ivi genes have already been implicated to play an important role in the pathogenesis of H.pylori and other bacterial pathogens such as Escherichia coli and Vibrio cholerae.Transcription profiles of all ivi genes were confirmed by real time PCR analysis of H.pylori RNA isolated from H.pylori infected RAW 264.7 macrophages.We compared the expression profile of H.pylori and RAW 264.7 coculture with that of H.pylori only

  14. Malaria-induced NLRP12/NLRP3-dependent caspase-1 activation mediates inflammation and hypersensitivity to bacterial superinfection.

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    Marco A Ataide

    2014-01-01

    Full Text Available Cyclic paroxysm and high fever are hallmarks of malaria and are associated with high levels of pyrogenic cytokines, including IL-1β. In this report, we describe a signature for the expression of inflammasome-related genes and caspase-1 activation in malaria. Indeed, when we infected mice, Plasmodium infection was sufficient to promote MyD88-mediated caspase-1 activation, dependent on IFN-γ-priming and the expression of inflammasome components ASC, P2X7R, NLRP3 and/or NLRP12. Pro-IL-1β expression required a second stimulation with LPS and was also dependent on IFN-γ-priming and functional TNFR1. As a consequence of Plasmodium-induced caspase-1 activation, mice produced extremely high levels of IL-1β upon a second microbial stimulus, and became hypersensitive to septic shock. Therapeutic intervention with IL-1 receptor antagonist prevented bacterial-induced lethality in rodents. Similar to mice, we observed a significantly increased frequency of circulating CD14(+CD16(-Caspase-1(+ and CD14(dimCD16(+Caspase-1(+ monocytes in peripheral blood mononuclear cells from febrile malaria patients. These cells readily produced large amounts of IL-1β after stimulation with LPS. Furthermore, we observed the presence of inflammasome complexes in monocytes from malaria patients containing either NLRP3 or NLRP12 pyroptosomes. We conclude that NLRP12/NLRP3-dependent activation of caspase-1 is likely to be a key event in mediating systemic production of IL-1β and hypersensitivity to secondary bacterial infection during malaria.

  15. Characterization of Chemically-Induced Bacterial Ghosts (BGs Using Sodium Hydroxide-Induced Vibrio parahaemolyticus Ghosts (VPGs

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    Hyun Jung Park

    2016-11-01

    Full Text Available Acellular bacterial ghosts (BGs are empty non-living bacterial cell envelopes, commonly generated by controlled expression of the cloned lysis gene E of bacteriophage PhiX174. In this study, Vibrio parahaemolyticus ghosts (VPGs were generated by chemically-induced lysis and the method is based on minimum inhibitory concentration (MIC of sodium hydroxide (NaOH, acetic acid, boric acid, citric acid, maleic acid, hydrochloric acid, and sulfuric acid. The MIC values of the respective chemicals were 3.125, 6.25, <50.0, 25.0, 6.25, 1.56, and 0.781 mg/mL. Except for boric acid, the lysis efficiency reached more than 99.99% at 5 min after treatment of all chemicals. Among those chemicals, NaOH-induced VPGs appeared completely DNA-free, which was confirmed by quantitative real-time PCR. Besides, lipopolysaccharides (LPS extracted from the NaOH-induced VPGs showed no distinctive band on SDS-PAGE gel after silver staining. On the other hand, LPS extracted from wild-type bacterial cells, as well as the organic acids-induced VPGs showed triple major bands and LPS extracted from the inorganic acids-induced VPGs showed double bands. It suggests that some surface structures in LPS of the NaOH-induced VPGs may be lost, weakened, or modified by the MIC of NaOH. Nevertheless, Limulus amoebocyte lysate assay revealed that there is no significant difference in endotoxic activity between the NaOH-induced VPGs and wild-type bacterial cells. Macrophages exposed to the NaOH-induced VPGs at 0.5 × 106 CFU/mL showed cell viability of 97.9%, however, the MIC of NaOH did not reduce the cytotoxic effect of wild-type bacterial cells. Like Escherichia coli LPS, the NaOH-induced VPGs are an excellent activator of pro-inflammatory cytokines (IL-1β and iNOS, anti-inflammatory cytokine (IL-10, and dual activities (IL-6 in the stimulated macrophage cells. On the other hand, the induction of TNF-α mRNA was remarkable in the macrophages exposed with wild-type cells. Scanning

  16. Bacterial flagellin induces IL-6 expression in human basophils.

    Science.gov (United States)

    Jeon, Jun Ho; Ahn, Ki Bum; Kim, Sun Kyung; Im, Jintaek; Yun, Cheol-Heui; Han, Seung Hyun

    2015-05-01

    Binding of allergen to IgE on basophils positively affects allergic inflammation by releasing inflammatory mediators. Recently, basophils were shown to express pattern-recognition receptors, such as toll-like receptors (TLRs), for recognizing microbe-associated molecular patterns (MAMPs) that are independent of allergen-IgE binding. In this study, we investigated whether MAMP alone can induce IL-6 production in a human basophil cell line, KU812. Stimulation with flagellin in the absence of allergen-IgE association induced IL-6 expression in KU812 cells, while stimulation with lipoteichoic acid, peptidoglycan, or poly I:C did not under the same condition. Flagellin-induced IL-6 expression was also observed in human primary basophils. Flow cytometric analysis showed that KU812 cells expressed flagellin-recognizing TLR5 both on the cell surface and in the cytoplasm while TLR2 and TLR3 were observed only in the cytoplasm. We further demonstrated that although flagellin augmented the phosphorylation of mitogen-activated protein kinases including p38 kinase, ERK, and JNK, flagellin-induced IL-6 production was attenuated by inhibitors for p38 kinase and ERK, but not by JNK inhibitors. In addition, flagellin enhanced phosphorylation of signaling molecules including CREB, PKCδ, and AKT. The inhibitors for PKA and PKC also showed inhibitory effects. Interestingly, flagellin-induced IL-6 production was further enhanced by pretreatment with inhibitors for PI3K, implying that PI3K negatively affects the flagellin-induced IL-6 production. Furthermore, DNA binding activities of NF-κB, AP-1, and CREB, which play pivotal roles in the induction of IL-6 gene expression, were increased by flagellin. These results suggest that flagellin alone is sufficient to induce IL-6 gene expression via TLR5 signaling pathways in human basophils.

  17. [The practice guideline 'Bacterial skin infections' (first revision) from the Dutch College of General Practitioners; a response from the perspective of general practice

    NARCIS (Netherlands)

    Olde Hartman, T.C.; Uijen, A.A.

    2008-01-01

    The revised guideline 'Bacterial skin infections' from the Dutch College ofGeneral Practitioners offers a clear and extensive overview of the most prevalent superficial and deep bacterial infections in general practice. Given the lack of evidence, it is no longer recommended to keep children with im

  18. BACTERIAL CAUSES OF LOWER RESPIRATORY TRACT INFECTIONS IN PATIENTS ATTENDING CENTRAL REFERRAL HOSPITAL, GANGTOK WITH REFERENCE TO ANTIBIOTIC RESISTANCE PATTERN

    OpenAIRE

    Priyanka Paul; Tukaram Prabhu

    2013-01-01

    ABSTRACT: BACKGROUND: There is inadequate information from India on various lower respiratory tract pathogens and their resistance pattern in hospital settings. The present study was undertaken to see the bacteriological profile an d the antibiotic resistance pattern of the isolates causing LRTI from this geographic region. OBJECTIVE: To identify and characterize bacterial pathogens causing community acquired and hospital acquired infections with reference to ant...

  19. Effect of long-term voluntary exercise wheel running on susceptibility to bacterial pulmonary infections in a mouse model.

    Directory of Open Access Journals (Sweden)

    Pauline B van de Weert-van Leeuwen

    Full Text Available Regular moderate exercise has been suggested to exert anti-inflammatory effects and improve immune effector functions, resulting in reduced disease incidence and viral infection susceptibility. Whether regular exercise also affects bacterial infection susceptibility is unknown. The aim of this study was to investigate whether regular voluntary exercise wheel running prior to a pulmonary infection with bacteria (P. aeruginosa affects lung bacteriology, sickness severity and phagocyte immune function in mice. Balb/c mice were randomly placed in a cage with or without a running wheel. After 28 days, mice were intranasally infected with P. aeruginosa. Our study showed that regular exercise resulted in a higher sickness severity score and bacterial (P. aeruginosa loads in the lungs. The phagocytic capacity of monocytes and neutrophils from spleen and lungs was not affected. Although regular moderate exercise has many health benefits, healthy mice showed increased bacterial (P. aeruginosa load and symptoms, after regular voluntary exercise, with perseverance of the phagocytic capacity of monocytes and neutrophils. Whether patients, suffering from bacterial infectious diseases, should be encouraged to engage in exercise and physical activities with caution requires further research.

  20. Relative roles of the cellular and humoral responses in the Drosophila host defense against three gram-positive bacterial infections.

    NARCIS (Netherlands)

    Nehme, N.T.; Quintin, J.; Cho, J.H.; Lee, J.; Lafarge, M.C.; Kocks, C.; Ferrandon, D.

    2011-01-01

    BACKGROUND: Two NF-kappaB signaling pathways, Toll and immune deficiency (imd), are required for survival to bacterial infections in Drosophila. In response to septic injury, these pathways mediate rapid transcriptional activation of distinct sets of effector molecules, including antimicrobial pepti

  1. A systematic literature review of the economic implications of acute bacterial skin and skin structure infections (ABSSSIs)

    NARCIS (Netherlands)

    Degener, F.; Ivanescu, C.; Casamayor, M.; Postma, M.

    2015-01-01

    Objectives: During the years, acute bacterial skin and skin structure infections (ABSSSIs) have seen an increase in incidence in many parts of the western world. Additionally, the treatment of ABSSSIs, generally consisting of surgical debridement or drainage and empiric antibiotics in the hospital,

  2. 细胞自噬治疗细菌感染的潜在价值%The potential application of autophagy in the treatment of bacterial infections

    Institute of Scientific and Technical Information of China (English)

    熊励晶; 童煜; 毛萌

    2011-01-01

    As a highly evolutionarily conserved cellular process, autophagy plays a critical role in maintaining cell homeostasis and promoting cellular survival via degradation of long-life proteins and damaged organdies. Autophagy induced by certain bacteria not only benefits the elimination of pathogen, but also limits toxin-induced cellular damage. Therefore, utilization of autophagy as a therapeutic and prophylactic approach for bacterial infections is in accordonce with its function of cell-autonomous defense mechanism. In this paper, we review the recent progress for the association between autophagy and bacterial infections in order to explore the potential application in treatment of bacterial infections.%细胞自噬是具进化保守性的细胞适应性机制,能降解细胞内容物,维持细胞稳态,保证细胞的生存.当细胞面临某些细菌感染时,自噬通过直接包裹胞质内游离的细菌、帮助吞噬体清除其包含的细菌、抵抗细菌毒素等方式保护受感染细胞.因此,将自噬抵抗细菌的作用应用于治疗和预防感染性疾病具有一定的可行性.本文将自噬在细菌感染中的作用及其治疗感染性疾病的潜在价值进行综述.

  3. Antibiofilm and anti-infection of a marine bacterial exopolysaccharide against Pseudomonas aeruginosa.

    Directory of Open Access Journals (Sweden)

    Shimei eWu

    2016-02-01

    Full Text Available Pseudomonas aeruginosa is a well-known pathogenic bacterium that forms biofilms and produces virulence factors, thus leading to major problems in many fields, such as clinical infection, food contamination and marine biofouling. In this study, we report the purification and characterization of an exopolysaccharide EPS273 from the culture supernatant of marine bacterium Pseudomonas stutzeri 273. The exopolysaccharide EPS273 not only effectively inhibits biofilm formation but also disperses preformed biofilm of Pseudomonas aeruginosa PAO1. High performance liquid chromatography traces of the hydrolyzed polysaccharides shows that EPS273 primarily consists of glucosamine, rhamnose, glucose and mannose. Further investigation demonstrates that EPS273 reduces the production of the virulence factors pyocyanin, exoprotease and rhamnolipid, and the virulence of P. aeruginosa PAO1 to human lung cells A549 and zebrafish embryos is also obviously attenuated by EPS273. In addition, EPS273 also greatly reduces the production of hydrogen peroxide (H2O2 and extracellular DNA (eDNA, which are important factors for biofilm formation. Furthermore, EPS273 exhibits strong antioxidant potential by quenching hydroxyl and superoxide anion radicals. Notably, the antibiofouling activity of EPS273 is observed in the marine environment up to two weeks according to the amounts of bacteria and diatoms in the glass slides submerged in the ocean. Taken together, the properties of EPS273 indicate that it has a promising prospect in combating bacterial biofilm-associated infection, food-processing contamination and marine biofouling.

  4. Microfluidic system for the identification of bacterial pathogens causing urinary tract infections

    Science.gov (United States)

    Becker, Holger; Hlawatsch, Nadine; Haraldsson, Tommy; van der Wijngaart, Wouter; Lind, Anders; Malhotra-Kumar, Surbi; Turlej-Rogacka, Agata; Goossens, Herman

    2015-03-01

    Urinary tract infections (UTIs) are among the most common bacterial infections and pose a significant healthcare burden. The growing trend in antibiotic resistance makes it mandatory to develop diagnostic kits which allow not only the determination of a pathogen but also the antibiotic resistances. We have developed a microfluidic cartridge which takes a direct urine sample, extracts the DNA, performs an amplification using batch-PCR and flows the sample over a microarray which is printed into a microchannel for fluorescence detection. The cartridge is injection-molded out of COP and contains a set of two-component injection-molded rotary valves to switch between input and to isolate the PCR chamber during thermocycling. The hybridization probes were spotted directly onto a functionalized section of the outlet microchannel. We have been able to successfully perform PCR of E.coli in urine in this chip and perform a fluorescence detection of PCR products. An upgraded design of the cartridge contains the buffers and reagents in blisters stored on the chip.

  5. Prevalence and antibiogram of bacterial isolates from urinary tract infections at Dessie Health Research Laboratory, Ethiopia

    Institute of Scientific and Technical Information of China (English)

    Mulugeta Kibret; Bayeh Abera

    2014-01-01

    Objective: To determine the prevalence and antimicrobial susceptibility of bacteria from suspected urinary tract infections.Methods:A retrospective analysis of bacterial pathogens and their antimicrobial susceptibility was done on urine samples at Dessie Regional Laboratory in the period 2003 to 2010. Antimicrobial susceptibility tests were done using disc diffusion technique as per the standard of Kirby-Bauer method.Results:The male to female ratio of the patients was 1:1.96. Of the total 1404 samples, 319 (22.7%) were culture positive. Escherichia coli was the dominant isolate (63.6%) followed by Klebsiella spp. (8.5%) and Proteus spp. (8.2%). The overall resistance rates to erythromycin, amoxycillin, and tetracycline were 85.6%, 88.9% and 76.7%, respectively. The three most frequently isolated bacteria had resistance rates of 80.1%-90.0% to, amoxycillin, and tetracycline and sensitivity rates of 0 to 25% to nitrofurantoin, ciprofloxacin and gentamicin. Antibiogram of isolates showed that 152 (47.85%) isolates were resistance to two and more antimicrobials.Conclusions:In the study area resistance rates to erythromycin, amoxycillin and tetracycline were high. Since most isolates were sensitive to nitrofurantoin and gentamicin, they are considered as appropriate antimicrobials for empirical treatment urinary tract infections.

  6. Prevalence of Selected Bacterial Infections Associated with the Use of Animal Waste in Louisiana

    Directory of Open Access Journals (Sweden)

    Paul B. Tchounwou

    2005-04-01

    Full Text Available Human health is a major concern when considering the disposal of large quantities of animal waste. Health concerns could arise from exposure to pathogens and excess nitrogen associated with this form of pollution. The objective was to collect and analyze health data related to selected bacterial infections associated with the use of animal waste in Louisiana. An analysis of adverse health effects has been conducted based on the incidence/prevalence rates of campylobacteriosis, E. coli O157:H7 infection, salmonellosis and shigellosis. The number of reported cases increased during the summer months. Analysis of health data showed that reported disease cases of E. coli O157:H7 were highest among Caucasian infants in the 0-4 year old age category and in Caucasian children in the 5-9 year old age category. Fatalities resulting from salmonellosis are low and increases sharply with age. The number of reported cases of shigellosis was found to be higher in African American males and females than in Caucasians. The high rate of identification in the younger population may result from the prompt seeking of medical care, as well as the frequent ordering of stool examination when symptoms become evident among this group of the population. The association with increasing age and fatality due to salmonellosis could be attributed to declining health and weaker immune systems often found in the older population. It is concluded that both animal waste and non-point source pollution may have a significant impact on human health.

  7. Can immunostimulants efficiently replace antibiotic in striped catfish (Pangasianodon hypophthalmus) against bacterial infection by Edwardsiella ictaluri?

    Science.gov (United States)

    Bich Hang, Bui Thi; Phuong, Nguyen Thanh; Kestemont, Patrick

    2014-10-01

    The present study was performed to determine the efficacy of lipopolysaccharide (LPS) and levamisole on immune response and disease resistance in striped catfish and to compare their respective efficiency with the one of an antibiotic treatment after infection of fish by the bacteria Edwardsiella ictaluri. Fish were divided into 3 groups and each group was injected with LPS (3 mg/kg fish), levamisole (5 mg/kg fish) or phosphate buffer saline as control. At day 21st post immunostimulant injection, fish were bled for assaying immunological variables and then challenged with E. ictaluri. Three days after bacterial infection, an antibiotic treatment was applied into fish subgroups and mortality was compared daily between antibiotic treated and untreated fish until 2 weeks post-challenge. LPS and levamisole significantly enhanced non-specific immune responses such as respiratory burst, lysozyme and complement activity in fish compared with control (p < 0.05). Respiratory burst and complement activity significantly increased in levamisole groups when compared with LPS groups while lysozyme activity did not differ significantly between immunostimulant treatments. Total immunoglobulins significantly increased in levamisole treatment compared with control. After challenge test, accumulated mortality was reduced significantly in both non-antibiotic and antibiotic subgroups of LPS and levamisole compared with control. Moreover, no differences of mortality were observed between fish treated with levamisole or LPS without antibiotics and control fish treated with antibiotics. These results support the possible replacement of antibiotics in striped catfish farming by immunostimulants such as levamisole and LPS.

  8. Critical role of tedizolid in the treatment of acute bacterial skin and skin structure infections

    Science.gov (United States)

    Ferrández, Olivia; Urbina, Olatz; Grau, Santiago

    2017-01-01

    Tedizolid phosphate has high activity against the Gram-positive microorganisms mainly involved in acute bacterial skin and skin structure infections, such as strains of Staphylococcus aureus (including methicillin-resistant S. aureus strains and methicillin-sensitive S. aureus strains), Streptococcus pyogenes, Streptococcus agalactiae, the Streptococcus anginosus group, and Enterococcus faecalis, including those with some mechanism of resistance limiting the use of linezolid. The area under the curve for time 0–24 hours/minimum inhibitory concentration (MIC) pharmacodynamic ratio has shown the best correlation with the efficacy of tedizolid, versus the time above MIC ratio and the maximum drug concentration/minimum inhibitory concentration ratio. Administration of this antibiotic for 6 days has shown its noninferiority versus administration of linezolid for 10 days in patients with skin and skin structure infections enrolled in two Phase III studies (ESTABLISH-1 and ESTABLISH-2). Tedizolid’s more favorable safety profile and dosage regimen, which allow once-daily administration, versus linezolid, position it as a good therapeutic alternative. However, whether or not the greater economic cost associated with this antibiotic is offset by its shorter treatment duration and possibility of oral administration in routine clinical practice has yet to be clarified. PMID:28053508

  9. Intravaginal practices, bacterial vaginosis, and HIV infection in women: individual participant data meta-analysis.

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    Nicola Low

    Full Text Available BACKGROUND: Identifying modifiable factors that increase women's vulnerability to HIV is a critical step in developing effective female-initiated prevention interventions. The primary objective of this study was to pool individual participant data from prospective longitudinal studies to investigate the association between intravaginal practices and acquisition of HIV infection among women in sub-Saharan Africa. Secondary objectives were to investigate associations between intravaginal practices and disrupted vaginal flora; and between disrupted vaginal flora and HIV acquisition. METHODS AND FINDINGS: We conducted a meta-analysis of individual participant data from 13 prospective cohort studies involving 14,874 women, of whom 791 acquired HIV infection during 21,218 woman years of follow-up. Data were pooled using random-effects meta-analysis. The level of between-study heterogeneity was low in all analyses (I(2 values 0.0%-16.1%. Intravaginal use of cloth or paper (pooled adjusted hazard ratio [aHR] 1.47, 95% confidence interval [CI] 1.18-1.83, insertion of products to dry or tighten the vagina (aHR 1.31, 95% CI 1.00-1.71, and intravaginal cleaning with soap (aHR 1.24, 95% CI 1.01-1.53 remained associated with HIV acquisition after controlling for age, marital status, and number of sex partners in the past 3 months. Intravaginal cleaning with soap was also associated with the development of intermediate vaginal flora and bacterial vaginosis in women with normal vaginal flora at baseline (pooled adjusted odds ratio [OR] 1.24, 95% CI 1.04-1.47. Use of cloth or paper was not associated with the development of disrupted vaginal flora. Intermediate vaginal flora and bacterial vaginosis were each associated with HIV acquisition in multivariable models when measured at baseline (aHR 1.54 and 1.69, p<0.001 or at the visit before the estimated date of HIV infection (aHR 1.41 and 1.53, p<0.001, respectively. CONCLUSIONS: This study provides evidence to

  10. Influence of exopolymeric materials on bacterially induced mineralization of carbonates.

    Science.gov (United States)

    Bains, Amrita; Dhami, Navdeep Kaur; Mukherjee, Abhijit; Reddy, M Sudhakara

    2015-04-01

    Microbially induced calcium carbonate precipitation is an immensely growing technology for restoration and remediation of building materials. The investigation on role of exopolymeric substances and biofilms in microbially induced calcium carbonate precipitation suggested that these exopolymeric materials play major role in carbonate precipitation in Bacillus megaterium SS3 along with enzymes urease and carbonic anhydrase. The concentration of EPS directly affects the precipitation of carbonate precipitates which might be due to capturing of Ca(2+) ions by acting as nucleation site. Components of the media and presence of calcium also play crucial role in production of exopolymeric substances along with affecting the morphology of carbonate precipitates.

  11. The accuracy of clinical symptoms and signs for the diagnosis of serious bacterial infection in young febrile children: prospective cohort study of 15 781 febrile illnesses

    OpenAIRE

    Craig, Jonathan C.; Williams, Gabrielle J; Jones, Mike; Codarini, Miriam; Macaskill, Petra; Hayen, Andrew; Irwig, Les; Fitzgerald, Dominic A; Isaacs, David; McCaskill, Mary

    2010-01-01

    Objectives To evaluate current processes by which young children presenting with a febrile illness but suspected of having serious bacterial infection are diagnosed and treated, and to develop and test a multivariable model to distinguish serious bacterial infections from self limiting non-bacterial illnesses. Design Two year prospective cohort study. Setting The emergency department of The Children’s Hospital at Westmead, Westmead, Australia. Participants Children aged less than 5 years pres...

  12. [Accuracy of PCR for the detection of bacterial and fungal DNA in the blood and tissue samples of experimentally infected rabbits].

    Science.gov (United States)

    Fouad, Ali Adil; Kalkancı, Ayşe

    2012-10-01

    Direct demonstration of bacterial and/or fungal nucleic acids in the clinical samples of patients with blood stream infections is crucial in terms of rapid diagnosis, early and accurate therapy and patient management. This study was aimed to determine the presence of bacteria and fungi by polymerase chain reaction (PCR) in the clinical samples of experimental sepsis induced animals, to compare the results with culture and to evaluate the efficiency of PCR in the discrimination of bacteremia and fungemia. A total of 12 rabbits experimentally infected with standard strains of Staphylococcus aureus, Escherichia coli, Aspergillus fumigatus and Candida albicans to generate bacteremia (n= 4), fungemia (n= 4) and polymicrobial blood stream infection (n= 4), were included in the study. A total of 63 specimens of which 27 were blood and 36 were tissue (12 spleen, 12 liver, 12 kidney) samples were collected at 24, 48, 72 and 96th hours of infection. Uninfected healthy rabbits (n= 4), colony suspensions of standard bacterial and fungal strains (n= 15) and human blood samples contaminated with standard bacterial and fungal strains (n= 10) were used as controls. Microbial DNAs were searched by using real-time PCR in all the samples, and quantitative cultures were performed simultaneously. Gram-positive and gram-negative PCR protocols were performed for the samples of bacteremic animals, whereas panfungal PCR, Aspergillus and Candida PCR protocols were performed for the samples of animals with fungemia. All of those PCR protocols were applied separately for the samples of polymicrobial blood stream infection cases. Culture positivity was detected in 8 (29.6%) of the blood samples and bacterial and/or fungal DNAs were demonstrated in 20 (74%) of the blood samples by PCR. Microbial DNAs were also detected in 32 (89%) of 36 tissue samples (11 spleen, 11 liver, 10 kidney). Sensitivity rates of culture method to detect bacteremia and fungemia were 30% and 21.7%, respectively, whereas

  13. Rapid label-free identification of mixed bacterial infections by surface plasmon resonance

    Directory of Open Access Journals (Sweden)

    Fu Weiling

    2011-06-01

    Full Text Available Abstract Background Early detection of mixed aerobic-anaerobic infection has been a challenge in clinical practice due to the phenotypic changes in complex environments. Surface plasmon resonance (SPR biosensor is widely used to detect DNA-DNA interaction and offers a sensitive and label-free approach in DNA research. Methods In this study, we developed a single-stranded DNA (ssDNA amplification technique and modified the traditional SPR detection system for rapid and simultaneous detection of mixed infections of four pathogenic microorganisms (Pseudomonas aeruginosa, Staphylococcus aureus, Clostridium tetani and Clostridium perfringens. Results We constructed the circulation detection well to increase the sensitivity and the tandem probe arrays to reduce the non-specific hybridization. The use of 16S rDNA universal primers ensured the amplification of four target nucleic acid sequences simultaneously, and further electrophoresis and sequencing confirmed the high efficiency of this amplification method. No significant signals were detected during the single-base mismatch or non-specific probe hybridization (P 2 values of >0.99. The lowest detection limits were 0.03 nM for P. aeruginosa, 0.02 nM for S. aureus, 0.01 nM for C. tetani and 0.02 nM for C. perfringens. The SPR biosensor had the same detection rate as the traditional culture method (P Conclusions Our method can rapidly and accurately identify the mixed aerobic-anaerobic infection, providing a reliable alternative to bacterial culture for rapid bacteria detection.

  14. Gene expression regulation in retinal pigment epithelial cells induced by viral RNA and viral/bacterial DNA

    Science.gov (United States)

    Brosig, Anton; Kuhrt, Heidrun; Wiedemann, Peter; Kohen, Leon; Bringmann, Andreas

    2015-01-01

    Purpose The pathogenesis of age-related macular degeneration (AMD) is associated with systemic and local inflammation. Various studies suggested that viral or bacterial infection may aggravate retinal inflammation in the aged retina. We compared the effects of synthetic viral RNA (poly(I:C)) and viral/bacterial DNA (CpG-ODN) on the expression of genes known to be involved in the development of AMD in retinal pigment epithelial (RPE) cells. Methods Cultured human RPE cells were stimulated with poly(I:C; 500 µg/ml) or CpG-ODN (500 nM). Alterations in gene expression and protein secretion were determined with real-time RT–PCR and ELISA, respectively. Phosphorylation of signal transduction molecules was revealed by western blotting. Results Poly(I:C) induced gene expression of the pattern recognition receptor TLR3, transcription factors (HIF-1α, p65/NF-κB), the angiogenic factor bFGF, inflammatory factors (IL-1β, IL-6, TNFα, MCP-1, MIP-2), and complement factors (C5, C9, CFB). Poly(I:C) also induced phosphorylation of ERK1/2 and p38 MAPK proteins, and the secretion of bFGF and TNFα from the cells. CpG-ODN induced moderate gene expression of transcription factors (p65/NF-κB, NFAT5) and complement factors (C5, C9), while it had no effect on the expression of various TLR, angiogenic factor, and inflammatory factor genes. The activities of various signal transduction pathways and transcription factors were differentially involved in mediating the poly(I:C)-induced transcriptional activation of distinct genes. Conclusions The widespread effects of viral RNA, and the restricted effects of viral/bacterial DNA, on the gene expression pattern of RPE cells may suggest that viral RNA rather than viral/bacterial DNA induces physiologic alterations of RPE cells, which may aggravate inflammation in the aged retina. The data also suggest that selective inhibition of distinct signal transduction pathways or individual transcription factors may not be effective to inhibit

  15. Target Product Profile for a Diagnostic Assay to Differentiate between Bacterial and Non-Bacterial Infections and Reduce Antimicrobial Overuse in Resource-Limited Settings: An Expert Consensus.

    Science.gov (United States)

    Dittrich, Sabine; Tadesse, Birkneh Tilahun; Moussy, Francis; Chua, Arlene; Zorzet, Anna; Tängdén, Thomas; Dolinger, David L; Page, Anne-Laure; Crump, John A; D'Acremont, Valerie; Bassat, Quique; Lubell, Yoel; Newton, Paul N; Heinrich, Norbert; Rodwell, Timothy J; González, Iveth J

    2016-01-01

    Acute fever is one of the most common presenting symptoms globally. In order to reduce the empiric use of antimicrobial drugs and improve outcomes, it is essential to improve diagnostic capabilities. In the absence of microbiology facilities in low-income settings, an assay to distinguish bacterial from non-bacterial causes would be a critical first step. To ensure that patient and market needs are met, the requirements of such a test should be specified in a target product profile (TPP). To identify minimal/optimal characteristics for a bacterial vs. non-bacterial fever test, experts from academia and international organizations with expertise in infectious diseases, diagnostic test development, laboratory medicine, global health, and health economics were convened. Proposed TPPs were reviewed by this working group, and consensus characteristics were defined. The working group defined non-severely ill, non-malaria infected children as the target population for the desired assay. To provide access to the most patients, the test should be deployable to community health centers and informal health settings, and staff should require 90% and >80% for sensitivity and specificity, respectively. Other key characteristics, to account for the challenging environment at which the test is targeted, included: i) time-to-result targeted and timely efforts by industry partners and academic institutions.

  16. The Value of the “Lab-Score” Method in Identifying Febrile Infants at Risk for Serious Bacterial Infections

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    Moldovan Diana Aniela

    2015-03-01

    Full Text Available Introduction: Most children with fever without source will have a self limited viral infection though a small percent will develop a serious bacterial infection (SBI like urinary tract infection, pneumonia, bacteraemia, meningitis or sepsis. The challenge facing practitioners is to distinguish between these two groups and currently biomarkers, like C-reactive protein (CRP and Procalcitonin (PCT, are available for this purpose. The aim of the current study was to identify SBI in infants with fever without an identifiable cause using the recently introduced “Lab-score” combining C-reactive protein, procalcitonin and urine dipstick results.

  17. Augmentation of Cationic Antimicrobial Peptide Production with Histone Deacetylase Inhibitors as a Novel Epigenetic Therapy for Bacterial Infections

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    Roshan D. Yedery

    2015-01-01

    Full Text Available The emergence of antibiotic resistance seriously threatens our ability to treat many common and medically important bacterial infections. Novel therapeutics are needed that can be used alone or in conjunction with antibiotics. Cationic antimicrobial peptides (CAMPs are important effectors of the host innate defense that exhibit broad-spectrum activity against a wide range of microorganisms. CAMPs are carried within phagocytic granules and are constitutively or inducibly expressed by multiple cell types, including epithelial cells. The role of histone modification enzymes, specifically the histone deacetylases (HDAC, in down-regulating the transcription of CAMP-encoding genes is increasingly appreciated as is the capacity of HDAC inhibitors (HDACi to block the action of HDACs to increase CAMP expression. The use of synthetic and natural HDACi molecules to increase CAMPs on mucosal surfaces, therefore, has potential therapeutic applications. Here, we review host and pathogen regulation of CAMP expression through the induction of HDACs and assess the therapeutic potential of natural and synthetic HDACi based on evidence from tissue culture systems, animal models, and clinical trials.

  18. The contribution of endogenous and exogenous effects to radiation-induced damage in the bacterial spore.

    Science.gov (United States)

    Jacobs, G P; Samuni, A; Czapski, G

    1985-06-01

    Radical scavengers such as polyethylene glycol 400 and 4000 and bovine albumin have been used to define the contribution of exogenous and endogenous effects to the gamma-radiation-induced damage in aqueous buffered suspensions of Bacillus pumilus spores. The results indicate that this damage in the bacterial spore is predominantly endogenous both in the presence of 1 atmosphere of oxygen, and in anoxia.

  19. Contribution of endogenous and exogenous effects to radiation-induced damage in the bacterial spore

    Energy Technology Data Exchange (ETDEWEB)

    Jacobs, G.P. (Hebrew Univ., Jerusalem (Israel). School of Pharmacy); Samuni, A. (Hebrew Univ., Jerusalem (Israel). School of Medicine); Czapski, G. (Hebrew Univ., Jerusalem (Israel). Dept. of Physical Chemistry)

    1985-06-01

    Radical scavengers such as polyethylene glycol 400 and 4000 and bovine albumin have been used to define the contribution of exogenous and endogenous effects to the gamma-radiation-induced damage in aqueous buffered suspensions of Bacillus pumilus spores. The results indicate that this damage in the bacterial spore is predominantly endogenous both in the presence of 1 atmosphere of oxygen, and in anoxia.

  20. Surveillance of bacterial and fungal infections in the postoperative period following liver transplantation: a series from 2005-2011.

    Science.gov (United States)

    Sganga, G; Bianco, G; Fiori, B; Nure, E; Spanu, T; Lirosi, M C; Frongillo, F; Agnes, S

    2013-09-01

    Orthotopic liver transplantation (OLT) is a life-saving procedure for the treatment of many end-stage diseases, but infectious and acute rejection episodes remain major causes of morbidity and mortality. Bacterial and fungal infections can be due to intra-abdominal, biliary, respiratory, urinary, wound, central venous catheters (CVC) or unknown sources. Using the computerized database of our microbiology laboratory, we analyzed all the bacterial and fungal infections in the first three months following OLT among 151 consecutive adult recipients at single center between January 2005 and December 2011. Samples included blood, bile CVC, urine, and bronchoalveolar lavage (BAL) specimen. Culture and identification of the isolated microorganisms was done in accordance with standard microbiological procedures. Three hundred thirteen samples from the above sites showed positive results for gram-positive cocci (n = 137; 43.8%), gram-negative rods (n = 156; 49.8%), and Candida species (n = 19; 6.1%). One patient (0.3%) experienced a CVC-related infection caused by Fusarium oxysporum. Bacterial and particularly biliary tract infections seem to play major roles in morbidity and mortality in the first three months following OLT. The major contributors to patient morbidity and mortality were candidemia and/or invasive candidiasis mainly from the biliary tract and/or CVC-related infections.

  1. 噬菌体治疗创面细菌感染研究进展%Advances in the treatment of wound bacterial infection with phage

    Institute of Scientific and Technical Information of China (English)

    崔泽龙

    2015-01-01

    The treatment of wound bacterial infection is an extremely difficult problem in clinic, especially in patients with large wounds which are infected by multidrug resistant, pan-resistant or omni-resistant bacteria.In recent years, with a grim prospect of antibiotic resistance, phage therapy is re-valued by researchers after being ignored for nearly half a century.Phage therapy has made great achievements in prevention and control of bacterial infection of open wounds.This review is mainly focused on the latest research progress of phage therapy in wound bacterial infection.

  2. A rapid crosstalk of human gammadelta T cells and monocytes drives the acute inflammation in bacterial infections.

    Directory of Open Access Journals (Sweden)

    Matthias Eberl

    2009-02-01

    Full Text Available Vgamma9/Vdelta2 T cells are a minor subset of T cells in human blood and differ from other T cells by their immediate responsiveness to microbes. We previously demonstrated that the primary target for Vgamma9/Vdelta2 T cells is (E-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP, an essential metabolite produced by a large range of pathogens. Here we wished to study the consequence of this unique responsiveness in microbial infection. The majority of peripheral Vgamma9/Vdelta2 T cells shares migration properties with circulating monocytes, which explains the presence of these two distinct blood cell types in the inflammatory infiltrate at sites of infection and suggests that they synergize in anti-microbial immune responses. Our present findings demonstrate a rapid and HMB-PP-dependent crosstalk between Vgamma9/Vdelta2 T cells and autologous monocytes that results in the immediate production of inflammatory mediators including the cytokines interleukin (IL-6, interferon (IFN-gamma, tumor necrosis factor (TNF-alpha, and oncostatin M (OSM; the chemokines CCL2, CXCL8, and CXCL10; and TNF-related apoptosis-inducing ligand (TRAIL. Moreover, under these co-culture conditions monocytes differentiate within 18 hours into inflammatory dendritic cells (DCs with antigen-presenting functions. Addition of further microbial stimuli (lipopolysaccharide, peptidoglycan induces CCR7 and enables these inflammatory DCs to trigger the generation of CD4(+ effector alphabeta T cells expressing IFN-gamma and/or IL-17. Importantly, our in vitro model replicates the responsiveness to microbes of effluent cells from peritoneal dialysis (PD patients and translates directly to episodes of acute PD-associated bacterial peritonitis, where Vgamma9/Vdelta2 T cell numbers and soluble inflammatory mediators are elevated in patients infected with HMB-PP-producing pathogens. Collectively, these findings suggest a direct link between invading pathogens, microbe

  3. Oral mucosal lipids are antibacterial against Porphyromonas gingivalis, induce ultrastructural damage, and alter bacterial lipid and protein compositions.

    Science.gov (United States)

    Fischer, Carol L; Walters, Katherine S; Drake, David R; Dawson, Deborah V; Blanchette, Derek R; Brogden, Kim A; Wertz, Philip W

    2013-09-01

    Oral mucosal and salivary lipids exhibit potent antimicrobial activity for a variety of Gram-positive and Gram-negative bacteria; however, little is known about their spectrum of antimicrobial activity or mechanisms of action against oral bacteria. In this study, we examine the activity of two fatty acids and three sphingoid bases against Porphyromonas gingivalis, an important colonizer of the oral cavity implicated in periodontitis. Minimal inhibitory concentrations, minimal bactericidal concentrations, and kill kinetics revealed variable, but potent, activity of oral mucosal and salivary lipids against P. gingivalis, indicating that lipid structure may be an important determinant in lipid mechanisms of activity against bacteria, although specific components of bacterial membranes are also likely important. Electron micrographs showed ultrastructural damage induced by sapienic acid and phytosphingosine and confirmed disruption of the bacterial plasma membrane. This information, coupled with the association of treatment lipids with P. gingivalis lipids revealed via thin layer chromatography, suggests that the plasma membrane is a likely target of lipid antibacterial activity. Utilizing a combination of two-dimensional in-gel electrophoresis and Western blot followed by mass spectroscopy and N-terminus degradation sequencing we also show that treatment with sapienic acid induces upregulation of a set of proteins comprising a unique P. gingivalis stress response, including proteins important in fatty acid biosynthesis, metabolism and energy production, protein processing, cell adhesion and virulence. Prophylactic or therapeutic lipid treatments may be beneficial for intervention of infection by supplementing the natural immune function of endogenous lipids on mucosal surfaces.

  4. Oral mucosal lipids are antibacterial against Porphyromonas gingivalis, induce ultrastructural damage, and alter bacterial lipid and protein compositions

    Institute of Scientific and Technical Information of China (English)

    Carol L Fischer; Katherine S Walters; David R Drake; Deborah V Dawson; Derek R Blanchette; Kim A Brogden; Philip W Wertz

    2013-01-01

    Oral mucosal and salivary lipids exhibit potent antimicrobial activity for a variety of Gram-positive and Gram-negative bacteria;however, little is known about their spectrum of antimicrobial activity or mechanisms of action against oral bacteria. In this study, we examine the activity of two fatty acids and three sphingoid bases against Porphyromonas gingivalis, an important colonizer of the oral cavity implicated in periodontitis. Minimal inhibitory concentrations, minimal bactericidal concentrations, and kill kinetics revealed variable, but potent, activity of oral mucosal and salivary lipids against P. gingivalis, indicating that lipid structure may be an important determinant in lipid mechanisms of activity against bacteria, although specific components of bacterial membranes are also likely important. Electron micrographs showed ultrastructural damage induced by sapienic acid and phytosphingosine and confirmed disruption of the bacterial plasma membrane. This information, coupled with the association of treatment lipids with P. gingivalis lipids revealed via thin layer chromatography, suggests that the plasma membrane is a likely target of lipid antibacterial activity. Utilizing a combination of two-dimensional in-gel electrophoresis and Western blot followed by mass spectroscopy and N-terminus degradation sequencing we also show that treatment with sapienic acid induces upregulation of a set of proteins comprising a unique P. gingivalis stress response, including proteins important in fatty acid biosynthesis, metabolism and energy production, protein processing, cell adhesion and virulence. Prophylactic or therapeutic lipid treatments may be beneficial for intervention of infection by supplementing the natural immune function of endogenous lipids on mucosal surfaces.

  5. Myeloid Cell Sirtuin-1 Expression Does Not Alter Host Immune Responses to Gram-Negative Endotoxemia or Gram-Positive Bacterial Infection

    Science.gov (United States)

    Crotty Alexander, Laura E.; Marsh, Brenda J.; Timmer, Anjuli M.; Lin, Ann E.; Zainabadi, Kayvan; Czopik, Agnieszka; Guarente, Leonard; Nizet, Victor

    2013-01-01

    The role of sirtuin-1 (SIRT1) in innate immunity, and in particular the influence of SIRT1 on antimicrobial defense against infection, has yet to be reported but is important to define since SIRT1 inhibitors are being investigated as therapeutic agents in the treatment of cancer, Huntington’s disease, and autoimmune diseases. Given the therapeutic potential of SIRT1 suppression, we sought to characterize the role of SIRT1 in host defense. Utilizing both pharmacologic methods and a genetic knockout, we demonstrate that SIRT1 expression has little influence on macrophage and neutrophil antimicrobial functions. Myeloid SIRT1 expression does not change mortality in gram-negative toxin-induced shock or gram-positive bacteremia, suggesting that therapeutic suppression of SIRT1 may be done safely without suppression of myeloid cell-specific immune responses to severe bacterial infections. PMID:24386389

  6. Myeloid cell sirtuin-1 expression does not alter host immune responses to Gram-negative endotoxemia or Gram-positive bacterial infection.

    Directory of Open Access Journals (Sweden)

    Laura E Crotty Alexander

    Full Text Available The role of sirtuin-1 (SIRT1 in innate immunity, and in particular the influence of SIRT1 on antimicrobial defense against infection, has yet to be reported but is important to define since SIRT1 inhibitors are being investigated as therapeutic agents in the treatment of cancer, Huntington's disease, and autoimmune diseases. Given the therapeutic potential of SIRT1 suppression, we sought to characterize the role of SIRT1 in host defense. Utilizing both pharmacologic methods and a genetic knockout, we demonstrate that SIRT1 expression has little influence on macrophage and neutrophil antimicrobial functions. Myeloid SIRT1 expression does not change mortality in gram-negative toxin-induced shock or gram-positive bacteremia, suggesting that therapeutic suppression of SIRT1 may be done safely without suppression of myeloid cell-specific immune responses to severe bacterial infections.

  7. Bacteria-induced or bacterial product-induced preterm parturition in mice and rabbits is preceded by a significant fall in serum progesterone concentrations.

    Science.gov (United States)

    Fidel, P I; Romero, R; Maymon, E; Hertelendy, F

    1998-01-01

    Bacterial products are thought to induce labor by stimulating the production of pro-inflammatory cytokines and prostaglandins in gestational tissues, leading to the onset of preterm parturition. Progesterone withdrawal is a prerequisite of parturition in many species. Yet a role for progesterone in the mechanisms responsible for preterm parturition, in the setting of infection, is unclear. The current studies were conducted to determine if a fall in serum progesterone concentrations occurs before the onset of bacterial product-induced preterm parturition in animals. Accordingly, pregnant mice at day 15 (70% gestation) were injected i.p. with Escherichia coli lipopolysaccharide (LPS; 50 microg/mouse) and timed-pregnant rabbits were inoculated transcervically with a suspension of E. coli to cause an ascending intrauterine infection. Control animals in both groups received equal volumes of sterile phosphate-buffered saline (PBS) solution. Blood specimens were collected at regular intervals and serum progesterone levels were determined by RIA. Within 14 h of LPS administration, mice delivered their pups. The median concentrations of serum progesterone were significantly lower at 1 h, 4 h, 10 h, and at the onset of preterm parturition (11-12 h) after LPS injection, compared to that in animals given PBS. Similarly, E. coli-inoculated rabbits delivered 1-2 days posttranscervical inoculation and demonstrated 60% decrease in serum progesterone within 12-24 h of inoculation compared to those given PBS. Parturition in both control groups occurred at term, following typical progesterone withdrawal. It is concluded that LPS administration to pregnant mice and ascending intrauterine infection in pregnant rabbits is associated with a dramatic fall in serum progesterone concentrations prior to the onset of parturition.

  8. Plant-activated bacterial receptor adenylate cyclases modulate epidermal infection in the Sinorhizobium meliloti-Medicago symbiosis.

    Science.gov (United States)

    Tian, Chang Fu; Garnerone, Anne-Marie; Mathieu-Demazière, Céline; Masson-Boivin, Catherine; Batut, Jacques

    2012-04-24

    Legumes and soil bacteria called rhizobia have coevolved a facultative nitrogen-fixing symbiosis. Establishment of the symbiosis requires bacterial entry via root hair infection threads and, in parallel, organogenesis of nodules that subsequently are invaded by bacteria. Tight control of nodulation and infection is required to maintain the mutualistic character of the interaction. Available evidence supports a passive bacterial role in nodulation and infection after the microsymbiont has triggered the symbiotic plant developmental program. Here we identify in Sinorhizobium meliloti, the Medicago symbiont, a cAMP-signaling regulatory cascade consisting of three receptor-like adenylate cyclases, a Crp-like regulator, and a target gene of unknown function. The cascade is activated specifically by a plant signal during nodule organogenesis. Cascade inactivation results in a hyperinfection phenotype consisting of abortive epidermal infection events uncoupled from nodulation. These findings show that, in response to a plant signal, rhizobia play an active role in the control of infection. We suggest that rhizobia may modulate the plant's susceptibility to infection. This regulatory loop likely aims at optimizing legume infection.

  9. Critical role of ASC inflammasomes and bacterial type IV secretion system in caspase-1 activation and host innate resistance to Brucella abortus infection.

    Science.gov (United States)

    Gomes, Marco Tulio R; Campos, Priscila C; Oliveira, Fernanda S; Corsetti, Patricia P; Bortoluci, Karina R; Cunha, Larissa D; Zamboni, Dario S; Oliveira, Sergio C

    2013-04-01

    Pathogens are detected by innate immune receptors that, upon activation, orchestrate an appropriate immune response. Recent studies revealed the intracellular signaling cascades involved in the TLR-initiated immune response to Brucella abortus infection. However, no report has elucidated the role of inflammasome receptors in Brucella recognition. Therefore, we decided to investigate the function of NLRC4, NLRP3, and AIM2 in sensing Brucella. In this study, we showed that NLRC4 is not required to induce caspase-1 activation and further secretion of IL-1β by B. abortus in macrophages. In contrast, we determined that AIM2, which senses Brucella DNA, and NLRP3 are partially required for caspase-1 activation and IL-1β secretion. Additionally, mitochondrial reactive oxygen species induced by Brucella were implicated in IL-1β production. Furthermore, AIM2, NLRP3, ASC, and caspase-1 knockout mice were more susceptible to B. abortus infection than were wild-type animals, suggesting that multiple ASC-dependent inflammasomes contribute to host protection against infection. This protective effect is due to the inflammatory response caused by IL-1β and IL-18 rather than pyroptosis, because we observed augmented bacterial burden in IL-1R and IL-18 knockout mice. Finally, we determined that bacterial type IV secretion system VirB and live, but not heat-killed, Brucella are required for full inflammasome activation in macrophages during infection. Taken together, our results indicate that Brucella is sensed by ASC inflammasomes that collectively orchestrate a robust caspase-1 activation and proinflammatory response.

  10. Bacterial Vaginosis

    Science.gov (United States)

    ... Issues > Conditions > Sexually Transmitted > Bacterial Vaginosis Health Issues Listen Español Text Size Email Print Share Bacterial Vaginosis Page Content Bacterial vaginosis (BV) is the most common vaginal infection in sexually active teenaged girls . It appears to be caused by ...

  11. Selection of aptamers for use as radiopharmaceuticals in bacterial infection diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Ferreira, Ieda Mendes; Faria, Ligia Santana de; Correa, Cristiane Rodrigues; Andrade, Antero Silva Ribeiro de, E-mail: imendesf@yahoo.com.br, E-mail: antero@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)

    2013-07-01

    The difficulty in early detection of specific foci in the bacterial infection caused by bacteria has raised the need to search for new techniques for this purpose, since these foci require prolonged treatment with antibiotics and in some cases even drainage or, if applicable, removal of prostheses or grafts. Detection of bacterial infections by scintigraphy has the advantage that an image of the whole body could be obtained. This study aims to obtain aptamers specific bacteria for future use as radiopharmaceutical. The SELEX (Systematic Evolution of Ligands by Exponential Enrichment) methodology can generate oligonucleotides (aptamers) that are able to bind with high affinity and specificity to a specific target, from small molecules to complex proteins, by using rounds of enrichment and amplification. Aptamers can be labeled with different radionucleotides such as {sup 99m}Tc, {sup 18}F and {sup 32}P. In this study aptamers anti-peptidoglycan, the main component of the outer cell wall of bacteria, were obtained through SELEX. The SELEX started with a pool of ssDNA that had 10{sup 15}different sequences (library), each oligo has two fixed regions merging a portion of 25 random nucleotides. Initially, the library of ssDNA was incubated with peptidoglycan, for 1h at 37 dec C with stirring. Subsequently, amplification of oligonucleotides that were able to bind to peptidoglycan was performed by PCR (Polymerase Chain Reaction). The amplified oligonucleotides were again incubated with peptidoglycan, amplified and purified. At the end of 15 rounds of selection the oligonucleotides were cloned using TOPO plasmid and Escherichia coli strain Top10F'. The plasmid DNA from 40 colonies were extracted and quantified. The plasmids were sequenced using the sequencing MegaBase, and two different aptamers sequences were obtained from all clones. The aptamers obtained were synthesized and subsequently labeled with {sup 32}P in the 5' end. The labeled aptamers were incubated

  12. Bacterially induced precipitation of CaCO sub 3 : An example from studies of cyanobacterial mats

    Energy Technology Data Exchange (ETDEWEB)

    Chafetz, H.S.

    1990-04-30

    Bacteria induce the precipitation of calcium carbonate in the laboratory and in nature by altering their chemical environment. Geologists are recognizing the possibility that bacterially induced precipitates may form significant mineral deposits, unfortunately, there are currently no sound criteria by which they can be recognized in recent sediments, or in the rock record. Cultures of aerobic and facultative bacteria from cyanobacterial mats on Andros Island, Bahamas, and Baffin Bay, Texas, induced the precipitation of calcium carbonate under controlled conditions. Crusts, the largest features formed, are composed of 5--200{mu}m diameter bundles which are, in turn, composed of numerous individual crystals. The smallest observed features are 0.1--0.4{mu}m spheres and rods which comprise some individual crystals and crystal bundles. Crystal bundles resembling rhombohedra, tetragonal disphenoids, tetragonal dipyramids, and calcite dumbbells appear to be uniquely bacterial in origin, and they have all been observed in recent sediments. Swollen rods, discs, curved dumbbells, and 50--200{mu}m optically continuous crystals resembling brushes may be uniquely bacterial in origin, however, they have not been reported by other laboratories nor observed in natural settings. Presence of any of these forms in recent sediments should be taken as strong evidence for bacterial influence. Spheres and aragonite dumbbells have also been observed in natural environments, however, they are not always bacterial in origin. Precipitation of calcium carbonate occurs preferentially on dead cyanobacteria in the presence of bacteria. Lithification of algal mats to form stromatolites may take place in the zone of decaying organic matter due to bacterial activity.

  13. Value of bacterial culture of vaginal swabs in diagnosis of vaginal infections

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    Nenadić Dane

    2015-01-01

    Full Text Available Bacground/Aim. Vaginal and cervical swab culture is still very common procedure in our country’s everyday practice whereas simple and rapid diagnostic methods have been very rarely used. The aim of this study was to show that the employment of simple and rapid diagnostic tools [vaginal fluid wet mount microscopy (VFWMM, vaginal pH and potassium hydroxide (KOH test] offers better assessment of vaginal environment than standard microbiologic culture commonly used in Serbia. Methods. This prospective study included 505 asymptomatic pregnant women undergoing VFWMM, test with 10% KOH, determination of vaginal pH and standard culture of cervicovaginal swabs. Combining findings from the procedures was used to make diagnoses of bacterial vaginosis (BV and vaginitis. In addition, the number of polymorphonuclear leukocytes (PMN was determined in each sample and analyzed along with other findings. Infections with Candida albicans and Trichomonas vaginalis were confirmed or excluded by microscopic examination. Results. In 36 (6% patients cervicovaginal swab cultures retrieved several aerobes and facultative anaerobes, whereas in 52 (11% women Candida albicans was isolated. Based on VFWMM findings and clinical criteria 96 (19% women had BV, 19 (4% vaginitis, and 72 (14% candidiasis. Of 115 women with BV and vaginitis, pH 4.5 was found in 5, and of 390 with normal findings 83 (21% had vaginal pH 4.5. Elevated numbers of PMN were found in 154 (30% women - in 83 (54% of them VFWMM was normal. Specificity and sensitivity of KOH test and vaginal pH determination in defining pathological vaginal flora were 95% and 81%, and 79% and 91%, respectively. Conclusion. Cervicovaginal swab culture is expensive but almost non-informative test in clinical practice. The use of simpler and rapid methods as vaginal fluid wet mount microscopy, KOH test and vaginal pH offers better results in diagnosis, and probably in the treatment and prevention of sequels of vaginal

  14. Steroid hormone signaling is essential to regulate innate immune cells and fight bacterial infection in Drosophila.

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    Jennifer C Regan

    2013-10-01

    Full Text Available Coupling immunity and development is essential to ensure survival despite changing internal conditions in the organism. Drosophila metamorphosis represents a striking example of drastic and systemic physiological changes that need to be integrated with the innate immune system. However, nothing is known about the mechanisms that coordinate development and immune cell activity in the transition from larva to adult. Here, we reveal that regulation of macrophage-like cells (hemocytes by the steroid hormone ecdysone is essential for an effective innate immune response over metamorphosis. Although it is generally accepted that steroid hormones impact immunity in mammals, their action on monocytes (e.g. macrophages and neutrophils is still not well understood. Here in a simpler model system, we used an approach that allows in vivo, cell autonomous analysis of hormonal regulation of innate immune cells, by combining genetic manipulation with flow cytometry, high-resolution time-lapse imaging and tissue-specific transcriptomic analysis. We show that in response to ecdysone, hemocytes rapidly upregulate actin dynamics, motility and phagocytosis of apoptotic corpses, and acquire the ability to chemotax to damaged epithelia. Most importantly, individuals lacking ecdysone-activated hemocytes are defective in bacterial phagocytosis and are fatally susceptible to infection by bacteria ingested at larval stages, despite the normal systemic and local production of antimicrobial peptides. This decrease in survival is comparable to the one observed in pupae lacking immune cells altogether, indicating that ecdysone-regulation is essential for hemocyte immune functions and survival after infection. Microarray analysis of hemocytes revealed a large set of genes regulated at metamorphosis by EcR signaling, among which many are known to function in cell motility, cell shape or phagocytosis. This study demonstrates an important role for steroid hormone regulation of

  15. Adjunctive chemotherapy of infection-induced staghorn calculi.

    Science.gov (United States)

    Griffith, D P; Moskowitz, P A; Carlton, C E

    1979-06-01

    Bacteria induce urinary crystallization of struvite and carbonate-apatite as a by-product of ureolysis by urease. Eradication of infection and/or inhibition of urease with acetohydroxamic acid for 5 to 30 months retarded stone growth and brought about partial or comple dissolution of stones in 9 patients. Long-term chemotherapy with antimicrobial agents that achieve steril urine or acetohydroxamic acid in those patients with recalcitrant infection lessens the risk of recurrent calculogenesis.

  16. Bacterial virulence analysis using brine shrimp as an infection model in relation to the importance of quorum sensing and proteases.

    Science.gov (United States)

    Lee, Mi-Nan; Kim, Soo-Kyoung; Li, Xi-Hui; Lee, Joon-Hee

    2014-01-01

    Brine shrimp are aquatic crustaceans belonging to a genus of Artemia. This organism is widely used for testing the toxicity of chemicals. In this study, brine shrimp were evaluated as an infection model organism to study bacterial virulence. Artemia nauplii were infected with various pathogenic bacteria, such as Vibrio vulnificus, Pseudomonas aeruginosa, Burkholderia vietnamiensis, Staphylococcus aureus, and Escherichia coli, and the susceptibility to these bacteria was investigated by counting the survival of the infected nauplii. While all of the tested bacteria have significant virulence to brine shrimp, killing the nauplii in a few days, V. vulnificus showed the strongest virulence. P. aeruginosa also showed a dose-dependent virulence to brine shrimp, but the virulence was weaker than that of V. vulnificus. The virulence tests using the virulence-attenuated mutants of V. vulnificus and P. aeruginosa, such as quorum sensing (QS) mutants or protease-deficient mutants showed a significant attenuation of virulence, demonstrating that the QS mechanism is important in the virulence of these bacteria to brine shrimp. B. vietnamiensis, S. aureus, and E. coli were also virulent to brine shrimp and the virulence was correlated with dosage within 24 h under our conditions. Salmonella enterica Typhimurium and Bacillus subtilis were also virulent to brine shrimp, but the virulence was weak and slowly exerted compared with that of other bacteria. Taken together, we suggest that brine shrimp are a good infection model to assay bacterial virulence, especially for V. vulnificus and P. aeruginosa, and QS is important in the bacterial virulence to brine shrimp.

  17. S-layer proteins from Lactobacillus sp. inhibit bacterial infection by blockage of DC-SIGN cell receptor.

    Science.gov (United States)

    Prado Acosta, Mariano; Ruzal, Sandra M; Cordo, Sandra M

    2016-11-01

    Many species of Lactobacillus sp. possess Surface(s) layer proteins in their envelope. Among other important characteristics S-layer from Lactobacillus acidophilus binds to the cellular receptor DC-SIGN (Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin; CD209), which is involved in adhesion and infection of several families of bacteria. In this report we investigate the activity of new S-layer proteins from the Lactobacillus family (Lactobacillus acidophilus, Lactobacillus brevis, Lactobacillus helveticus and Lactobacillus kefiri) over the infection of representative microorganisms important to human health. After the treatment of DC-SIGN expressing cells with these proteins, we were able to diminish bacterial infection by up to 79% in both gram negative and mycobacterial models. We discovered that pre-treatment of the bacteria with S-layers from Lactobacillus acidophilus and Lactobacillus brevis reduced bacteria viability but also prevent infection by the pathogenic bacteria. We also proved the importance of the glycosylation of the S-layer from Lactobacillus kefiri in the binding to the receptor and thus inhibition of infection. This novel characteristic of the S-layers proteins may contribute to the already reported pathogen exclusion activity for these Lactobacillus probiotic strains; and might be also considered as a novel enzymatic antimicrobial agents to inhibit bacterial infection and entry to host cells.

  18. Antimicrobial proteins from snake venoms: direct bacterial damage and activation of innate immunity against Staphylococcus aureus skin infection.

    Science.gov (United States)

    Samy, R P; Stiles, B G; Gopalakrishnakone, P; Chow, V T K

    2011-01-01

    The innate immune system is the first line of defense against microbial diseases. Antimicrobial proteins produced by snake venoms have recently attracted significant attention due to their relevance to bacterial infection and potential development into new therapeutic agents. Staphylococcus aureus is one of the major human pathogens causing a variety of infections involving pneumonia, toxic shock syndrome, and skin lesions. With the recent emergence of methicillin (MRSA) and vancomycin (VRSA) resistance, S. aureus infection is a serious clinical problem that will have a grave socio-economic impact in the near future. Although S. aureus susceptibility to innate antimicrobial peptides has been reported recently, the protective effect of snake venom phospholipase A₂ (svPLA₂) proteins on the skin from S. aureus infection has been understudied. This review details the protective function of svPLA₂s derived from venoms against skin infections caused by S. aureus. We have demonstrated in vivo that local application of svPLA₂ provides complete clearance of S. aureus within 2 weeks after treatment compared to fusidic acid ointment (FAO). In vitro experiments also demonstrate that svPLA₂ proteins have inhibitory (bacteriostatic) and killing (bactericidal) effects on S. aureus in a dose-dependant manner. The mechanism of bacterial membrane damage and perturbation was clearly evidenced by electron microscopic studies. In summary, svPLA₂s from Viperidae and Elapidae snakes are novel molecules that can activate important mechanisms of innate immunity in animals to endow them with protection against skin infection caused by S. aureus.

  19. ST2 negatively regulates TLR2 signaling, but is not required for bacterial lipoprotein-induced tolerance.

    LENUS (Irish Health Repository)

    Liu, Jinghua

    2010-05-15

    Activation of TLR signaling is critical for host innate immunity against bacterial infection. Previous studies reported that the ST2 receptor, a member of the Toll\\/IL-1 receptor superfamily, functions as a negative regulator of TLR4 signaling and maintains LPS tolerance. However, it is undetermined whether ST2 negatively regulates TLR2 signaling and furthermore, whether a TLR2 agonist, bacterial lipoprotein (BLP)-induced tolerance is dependent on ST2. In this study, we show that BLP stimulation-induced production of proinflammatory cytokines and immunocomplex formation of TLR2-MyD88 and MyD88-IL-1R-associated kinase (IRAK) were significantly enhanced in ST2-deficient macrophages compared with those in wild-type controls. Furthermore, overexpression of ST2 dose-dependently attenuated BLP-induced NF-kappaB activation, suggesting a negative regulatory role of ST2 in TLR2 signaling. A moderate but significantly attenuated production of TNF-alpha and IL-6 on a second BLP stimulation was observed in BLP-pretreated, ST2-deficient macrophages, which is associated with substantially reduced IRAK-1 protein expression and downregulated TLR2-MyD88 and MyD88-IRAK immunocomplex formation. ST2-deficient mice, when pretreated with a nonlethal dose of BLP, benefitted from an improved survival against a subsequent lethal BLP challenge, indicating BLP tolerance develops in the absence of the ST2 receptor. Taken together, our results demonstrate that ST2 acts as a negative regulator of TLR2 signaling, but is not required for BLP-induced tolerance.

  20. Anti-Pseudomonas aeruginosa IgY Antibodies Induce Specific Bacterial Aggregation and Internalization in Human Polymorphonuclear Neutrophils

    DEFF Research Database (Denmark)

    Thomsen, K; Christophersen, L; Bjarnsholt, T;

    2015-01-01

    Polymorphonuclear neutrophils (PMNs) are essential cellular constituents in the innate host response, and their recruitment to the lungs and subsequent ubiquitous phagocytosis controls primary respiratory infection. Cystic fibrosis pulmonary disease is characterized by progressive pulmonary decline...... with P. aeruginosa by augmenting the phagocytic competence of PMNs may postpone the deteriorating chronic biofilm infection. Anti-P. aeruginosa IgY antibodies significantly increase the PMN-mediated respiratory burst and subsequent bacterial killing of P. aeruginosa in vitro. The mode of action......, which enhances bacterial killing by PMN-mediated phagocytosis and thereby may facilitate a rapid bacterial clearance in airways of people with cystic fibrosis....

  1. Mycobacterium leprae-induced Insulin-like Growth Factor I attenuates antimicrobial mechanisms, promoting bacterial survival in macrophages

    Science.gov (United States)

    Batista-Silva, L. R.; Rodrigues, Luciana Silva; Vivarini, Aislan de Carvalho; Costa, Fabrício da Mota Ramalho; Mattos, Katherine Antunes de; Costa, Maria Renata Sales Nogueira; Rosa, Patricia Sammarco; Toledo-Pinto, T. G.; Dias, André Alves; Moura, Danielle Fonseca; Sarno, Euzenir Nunes; Lopes, Ulisses Gazos; Pessolani, Maria Cristina Vidal

    2016-01-01

    Mycobacterium leprae (ML), the etiologic agent of leprosy, can subvert macrophage antimicrobial activity by mechanisms that remain only partially understood. In the present study, the participation of hormone insulin-like growth factor I (IGF-I) in this phenomenum was investigated. Macrophages from the dermal lesions of the disseminated multibacillary lepromatous form (LL) of leprosy expressed higher levels of IGF-I than those from the self-limited paucibacillary tuberculoid form (BT). Higher levels of IGF-I secretion by ML-infected macrophages were confirmed in ex vivo and in vitro studies. Of note, the dampening of IGF-I signaling reverted the capacity of ML-infected human and murine macrophages to produce antimicrobial molecules and promoted bacterial killing. Moreover, IGF-I was shown to inhibit the JAK/STAT1-dependent signaling pathways triggered by both mycobacteria and IFN-γ most probably through its capacity to induce the suppressor of cytokine signaling-3 (SOCS3). Finally, these in vitro findings were corroborated by in vivo observations in which higher SOCS3 expression and lower phosphorylation of STAT1 levels were found in LL versus BT dermal lesions. Altogether, our data strongly suggest that IGF-I contributes to the maintenance of a functional program in infected macrophages that suits ML persistence in the host, reinforcing a key role for IGF-I in leprosy pathogenesis. PMID:27282338

  2. The inflammasomes: Molecular effectors of host resistance against bacterial, viral, parasitic and fungal infections

    Directory of Open Access Journals (Sweden)

    Alexander eSkeldon

    2011-02-01

    Full Text Available The inflammasomes are large multi-protein complexes scaffolded by cytosolic pattern recognition receptors (PRRs that form an important part of the innate immune system. They are activated following the recognition of microbial-associated molecular patterns (MAMPs or host-derived danger signals (danger-associated molecular patterns or DAMPs by PRRs. This recognition results in the recruitment and activation of the pro-inflammatory protease caspase-1, which cleaves its preferred substrates pro-interleukin-1β (IL-1β and pro-IL-18 into their mature biologically active cytokine forms. Through processing of a number of other cellular substrates, caspase-1 is also required for the release of alarmins and the induction and execution of an inflammatory form of cell death termed pyroptosis. A growing spectrum of inflammasomes have been identified in the host defence against a variety of pathogens. Reciprocally, pathogens have evolved effector strategies to antagonize the inflammasome pathway. In this review we discuss recent developments in the understanding of inflammasome-mediated recognition of bacterial, viral, parasitic and fungal infections and the beneficial or detrimental effects of inflammasome signalling in host resistance.

  3. Aptamers: Novel Molecules as Diagnostic Markers in Bacterial and Viral Infections?

    Directory of Open Access Journals (Sweden)

    Flávia M. Zimbres

    2013-01-01

    Full Text Available Worldwide the entire human population is at risk of infectious diseases of which a high degree is caused by pathogenic protozoans, worms, bacteria, and virus infections. Moreover the current medications against pathogenic agents are losing their efficacy due to increasing and even further spreading drug resistance. Therefore, there is an urgent need to discover novel diagnostic as well as therapeutic tools against infectious agents. In view of that, the Systematic Evolution of Ligands by Exponential Enrichment (SELEX represents a powerful technology to target selectively pathogenic factors as well as entire bacteria or viruses. SELEX uses a large combinatorial oligonucleic acid library (DNA or RNA which is processed a by high-flux in vitro screen of iterative cycles. The selected ligands, termed aptamers, are characterized by high specificity and affinity to their target molecule, which are already exploited in diagnostic and therapeutic applications. In this minireview we will discuss the current status of the SELEX technique applied on bacterial and viral pathogens.

  4. Susceptibility of Caenorhabditis elegans to Burkholderia infection depends on prior diet and secreted bacterial attractants.

    Directory of Open Access Journals (Sweden)

    Vaughn S Cooper

    Full Text Available The nematode Caenorhabditis elegans may be killed by certain pathogenic bacteria and thus is a model organism for studying interactions between bacteria and animal hosts. However, growing nematodes on prey bacteria may influence their susceptibility to potential pathogens. A method of axenic nematode culture was developed to isolate and quantify interactions between C. elegans and potentially pathogenic strains of the Burkholderia cepacia complex. Studying these dynamics in liquid solution rather than on agar surfaces minimized nematode avoidance behavior and resolved more differences among isolates. Most isolates of B. cenocepacia, B. ambifaria and B. cepacia caused 60-80% mortality of nematodes after 7 days, whereas isolates of B. multivorans caused less mortality (<25% and supported nematode reproduction. However, some B. cenocepacia isolates recovered from chronic infections were much less virulent (5-28% mortality. As predicted, prior diet altered the outcome of interactions between nematodes and bacteria. When given the choice between Burkholderia and E. coli as prey on agar, axenically raised nematodes initially preferred most lethal Burkholderia isolates to E. coli as a food source, but this was not the case for nematodes fed E. coli, which avoided toxic Burkholderia. This food preference was associated with the cell-free supernatant and thus secreted compounds likely mediated bacterial-nematode interactions. This model, which isolates interactions between bacteria and nematodes from the effects of prior feeding, demonstrates that bacteria can influence nematode behavior and their susceptibility to pathogens.

  5. Fungal innate immunity induced by bacterial microbe-associated molecular patterns (MAMPs)

    DEFF Research Database (Denmark)

    Ip Cho, Simon; Sundelin, Thomas; Erbs, Gitte

    2016-01-01

    Plants and animals detect bacterial presence through Microbe-Associated Molecular Patterns (MAMPs) which induce an innate immune response. The field of fungal-bacterial interaction at the molecular level is still in its infancy and little is known about MAMPs and their detection by fungi. Exposing...... Fusarium graminearum to bacterial MAMPs led to increased fungal membrane hyperpolarization, a putative defense response, and a range of transcriptional responses. The fungus reacted with a different transcript profile to each of the three tested MAMPs, although a core set of genes related to energy...... for further interactions with beneficial or pathogenic bacteria, and constitute a fungal innate immune response with similarities to those of plants and animals....

  6. Evaluating clinical periodontal measures as surrogates for bacterial exposure: The Oral Infections and Vascular Disease Epidemiology Study (INVEST

    Directory of Open Access Journals (Sweden)

    Jacobs David R

    2010-01-01

    Full Text Available Abstract Background Epidemiologic studies of periodontal infection as a risk factor for cardiovascular disease often use clinical periodontal measures as a surrogate for the underlying bacterial exposure of interest. There are currently no methodological studies evaluating which clinical periodontal measures best reflect the levels of subgingival bacterial colonization in population-based settings. We investigated the characteristics of clinical periodontal definitions that were most representative of exposure to bacterial species that are believed to be either markers, or themselves etiologic, of periodontal disease. Methods 706 men and women aged ≥ 55 years, residing in northern Manhattan were enrolled. Using DNA-DNA checkerboard hybridization in subgingival biofilms, standardized values for Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia were averaged within mouth and summed to define "bacterial burden". Correlations of bacterial burden with clinical periodontal constructs defined by the severity and extent of attachment loss (AL, pocket depth (PD and bleeding on probing (BOP were assessed. Results Clinical periodontal constructs demonstrating the highest correlations with bacterial burden were: i percent of sites with BOP (r = 0.62; ii percent of sites with PD ≥ 3 mm (r = 0.61; and iii number of sites with BOP (r = 0.59. Increasing PD or AL severity thresholds consistently attenuated correlations, i.e., the correlation of bacterial burden with the percent of sites with PD ≥ 8 mm was only r = 0.16. Conclusions Clinical exposure definitions of periodontal disease should incorporate relatively shallow pockets to best reflect whole mouth exposure to bacterial burden.

  7. Spatial and Temporal Shifts in Bacterial Biogeography and Gland Occupation during the Development of a Chronic Infection

    Science.gov (United States)

    Zavros, Yana; Shepherd, Benjamin; Salama, Nina R.

    2016-01-01

    ABSTRACT Gland colonization may be one crucial route for bacteria to maintain chronic gastrointestinal infection. We developed a quantitative gland isolation method to allow robust bacterial population analysis and applied it to the gastric pathobiont Helicobacter pylori. After infections in the murine model system, H. pylori populations multiply both inside and outside glands in a manner that requires the bacteria to be motile and chemotactic. H. pylori is able to achieve gland densities averaging 25 to 40 bacteria/gland after 2 to 4 weeks of infection. After 2 to 4 weeks of infection, a primary infection leads to colonization resistance for a secondary infection. Nonetheless, about ~50% of the glands remained unoccupied, suggesting there are as-yet unappreciated parameters that prevent gastric gland colonization. During chronic infections, H. pylori populations collapsed to nearly exclusive gland localization, to an average of <8 bacteria/gland, and only 10% of glands occupied. We analyzed an H. pylori chemotaxis mutant (Che−) to gain mechanistic insight into gland colonization. Che− strains had a severe inability to spread to new glands and did not protect from a secondary infection but nonetheless achieved a chronic gland colonization state numerically similar to that of the wild type. Overall, our analysis shows that bacteria undergo substantial population dynamics on the route to chronic colonization, that bacterial gland populations are maintained at a low level during chronic infection, and that established gland populations inhibit subsequent colonization. Understanding the parameters that promote chronic colonization will allow the future successful design of beneficial microbial therapeutics that are able to maintain long-term mammalian colonization. PMID:27729513

  8. A case of emphysematous pyelonephritis induced by Citrobacter freundii infection

    Directory of Open Access Journals (Sweden)

    Youichi Yanagawa

    2013-01-01

    Full Text Available A 79-year-old female with diabetes mellitus had general fatigue, a high fever and vomiting. A CT revealed acute emphysematous pyelonephritis (EPN. A nephrectomy was performed on the 2 nd hospital day. The results of the blood culture showed the presence of Citrobacter freundii infection. The patient′s post-operative course was uneventful. This case is the second reported case of EPN induced by Citrobacter freundii. Bacteremia induced by Citrobacter freundii infection typically results in a high mortality rate. In this case, the early diagnosis of the EPN using CT and immediate medical treatment, including urgent elective nephrectomy, were key to the favorable outcome.

  9. Saccharomyces boulardii prevention of the hepatic injury induced by Salmonella Enteritidis infection.

    Science.gov (United States)

    Wu, Daichao; Teng, Da; Wang, Xiumin; Dai, Changsong; Wang, Jianhua

    2014-10-01

    Salmonella enterica subsp. enterica serovar Enteritidis (Salmonella Enteritidis) is the predominant cause of serovar-associated food-borne outbreaks in many countries and causes significant clinical symptoms of liver injury, enteritis, and diarrheal diseases. Saccharomyces boulardii is used in clinical application for prophylaxis and the treatment of a variety of diseases caused by bacterial infection. We used a mouse model of Salmonella Enteritidis infection, which included pretreatment with S. boulardii, to reveal the protection mechanisms of S. boulardii against Salmonella Enteritidis infection, including the translocation of Salmonella Enteritidis to the liver 10 days after Salmonella Enteritidis challenge, and the colonisation of Salmonella Enteritidis and the formation of hepatic tissue lesions in mice after Salmonella Enteritidis challenge on the 10th day. Compared with Salmonella Enteritidis infection in mice, S. boulardii decreased Salmonella Enteritidis translocation to the liver by 96%, and 99% of Salmonella Enteritidis colonised the cecum on the 10th day. Saccharomyces boulardii also abated hepatic tissue injury caused by the infiltration of neutrophilic granulocytes, lymphocytes, and plasmocytes by decreasing the translocation of Salmonella to the liver. These findings demonstrated that S. boulardii is an effective agent in the prevention of the hepatic injury induced by Salmonella Enteritidis infection in a mouse model.

  10. Glibenclamide reduces pro-inflammatory cytokine production by neutrophils of diabetes patients in response to bacterial infection

    Science.gov (United States)

    Kewcharoenwong, Chidchamai; Rinchai, Darawan; Utispan, Kusumawadee; Suwannasaen, Duangchan; Bancroft, Gregory J.; Ato, Manabu; Lertmemongkolchai, Ganjana

    2013-11-01

    Type 2 diabetes mellitus is a major risk factor for melioidosis, which is caused by Burkholderia pseudomallei. Our previous study has shown that polymorphonuclear neutrophils (PMNs) from diabetic subjects exhibited decreased functions in response to B. pseudomallei. Here we investigated the mechanisms regulating cytokine secretion of PMNs from diabetic patients which might contribute to patient susceptibility to bacterial infections. Purified PMNs from diabetic patients who had been treated with glibenclamide (an ATP-sensitive potassium channel blocker for anti-diabetes therapy), showed reduction of interleukin (IL)-1β and IL-8 secretion when exposed to B. pseudomallei. Additionally, reduction of these pro-inflammatory cytokines occurred when PMNs from diabetic patients were treated in vitro with glibenclamide. These findings suggest that glibenclamide might be responsible for the increased susceptibility of diabetic patients, with poor glycemic control, to bacterial infections as a result of its effect on reducing IL-1β production by PMNs.

  11. Previous bacterial infection affects textural quality parameters of heat-treated fillets from rainbow trout (Oncorhynchus mykiss)

    DEFF Research Database (Denmark)

    Ingerslev, Hans-Christian; Hyldig, Grethe; Przybylska, Dominika Alicja

    2012-01-01

    Sensory quality of fish meat is influenced by many parameters prior to slaughter. In the present study, it was examined if previous infections or damages in the muscle tissue influence product quality parameters in fish. Fillets from rainbow trout (Oncorhynchus mykiss) reared in seawater at a com......-smoked instead of being sold as raw meat. The established correlation between disease history stresses the importance of disease prevention in aquaculture production, e.g., vaccination of the fish....... at a commercial fish farm were sensory evaluated for more than a year after recovery following physical tissue damage or infection by the bacterial pathogens Yersinia ruckeri and Vibrio anguillarum. The effect of vaccination was also included as some fish were vaccinated before bacterial challenge. The fish...

  12. Infecção bacteriana em pacientes portadores de Leishmaniase visceral Bacterial infection in patients with visceral leishmaniasis

    Directory of Open Access Journals (Sweden)

    Jaqueline Guerreiro

    1985-12-01

    Full Text Available Uma análise retrospectiva de 63 casos de Leishmaniose visceral (L.V. revelou a presença, em 33 deles, de infecção bacteriana associada. Infecções do trato respiratório foram observadas em 13 (39,3% pacientes, comprometimento de pele em 4 (12%, do trato urinário em 4 (12%, do ouvido em 3 (9%, e de orofaringe em 2 (6%. Sete (21% pacientes apresentaram infecção concomitante em múltiplos sítios. Documentação bacteriológica através de isolamneto do agente etiológico foi obtida em 10, não havendo predominância estatisticamente significante de bactérias Gram positivas ou negativas. Houve 9 casos de óbito nestes 63 pacientes, sendo que em 8 deles a infecção bacteriana fazia parte do quadro clínico final. A análise das taxas de globulinas séricas revelou que infecção esteve presente de modo significativo (p 0.05 com relação ao número de neutrófilos entre os grupos com e sem infecção bacteriana. Concluiu-se, portanto, que infecção bacteriana é um achado freqüente em pacientes com L.V. e se constitui num sinal de mau prognóstico da doença.In an analysis of 63 hospitalized cases with visceral leishmaniasis, the clinical or post-mortem diagnosis of bacterial infection was performed in 33; 13 (39.3% patients had respiratory infection, 4 (12.1% had skin infection, 4 had urinary tract infection, 3 (9.0% showed ear infection and 2 (6.6% had infection of the oral cavity. It is worth mentioning that in 7 (21% cases there was infection in multiple sites. Gram positive and/or Gram negative organisms were isolated from 10 patients. In only two (autopsied cases, infection with less common organisms was recorded, one with disseminated candidiasis and another with disseminated tuberculosis. Death occurred in 9 of the 63 cases, and in 8 of these, concomitant bacterial infection of importance was documented. Patients who had serum globulins lower than 4 g% had significantly more infection (p less than 0.05 than patients with

  13. Immunohistochemical analysis of MMP-9, MMP-2 and TIMP-1, TIMP-2 expression in the central nervous system following infection with viral and bacterial meningitis.

    Directory of Open Access Journals (Sweden)

    Lech Chyczewski

    2009-01-01

    Full Text Available Matrix metalloproteinases (MMPs are capable of degrading components of the basal lamina of cerebral vessels, thereby disrupting the blood-brain barrier and inducing leukocyte recruitment. This study provides comprehensive information regarding the cell specificity of matrix metalloproteinases (MMP-2, MMP-9 and their binding tissue inhibitors (TIMP-1, TIMP-2 in the central nervous system during viral and bacterial meningitis. Specifically, we evaluated the immunoreactivity of MMPs and TIMPs in various cell types in brain parenchyma and meninges obtained from autopsy tissues. We found that a higher proportion of endothelial cells were positive for MMP-9 during meningitis when compared to controls. In addition, the immunoreactivity of MMP-9 decreased and the immunoreactivity of TIMP-1 increased in astrocytes upon infection. Furthermore, the results of this study revealed that mononuclear cells were highly immunoreactive for TIMP-1, TIMP-2 and MMP-9 during viral meningitis and that the expression of TIMPs in polymorphonuclear cells was even higher during bacterial meningitis. Taken together the results of this study indicated that the central nervous system resident cells and inflammatory infiltrates contribute to MMPs activity and that the expression patterns vary between cell types and in response to viral and bacterial meningitis.

  14. A novel ion-beam-mutation effect application in identification of gene involved in bacterial antagonism to fungal infection of ornamental crops

    Science.gov (United States)

    Mahadtanapuk, S.; Teraarusiri, W.; Nanakorn, W.; Yu, L. D.; Thongkumkoon, P.; Anuntalabhochai, S.

    2014-05-01

    This work is on a novel application of ion beam effect on biological mutation. Bacillus licheniformis (B. licheniformis) is a common soil bacterium with an antagonistic effect on Curcuma alismatifolia Gagnep. and Chrysanthemum indicum Linn. In an attempt to control fungal diseases of local crops by utilizing B. licheniformis, we carried out gene analysis of the bacterium to understand the bacterial antagonistic mechanism. The bacterial cells were bombarded to induce mutations using nitrogen ion beam. After ion bombardment, DNA analysis revealed that the modified polymorphism fragment present in the wild type was missing in a bacterial mutant which lost the antifungal activity. The fragments conserved in the wild type but lost in the mutant bacteria was identified to code for the thioredoxin reductase (TrxR) gene. The gene analysis showed that the TrxR gene from B. licheniformis had the expression of the antagonism to fungi in a synchronous time evolution with the fungus inhibition when the bacteria were co-cultivated with the fungi. The collective results indicate the TrxR gene responsible for the antagonism of bacteria B. licheniformis to fungal infection.

  15. Immunohistochemical analysis of MMP-9, MMP-2 and TIMP-1, TIMP-2 expression in the central nervous system following infection with viral and bacterial meningitis.

    Science.gov (United States)

    Sulik, Artur; Chyczewski, Lech

    2008-01-01

    Matrix metalloproteinases (MMPs) are capable of degrading components of the basal lamina of cerebral vessels, thereby disrupting the blood-brain barrier and inducing leukocyte recruitment. This study provides comprehensive information regarding the cell specificity of matrix metalloproteinases (MMP-2, MMP-9) and their binding tissue inhibitors (TIMP-1, TIMP-2) in the central nervous system during viral and bacterial meningitis. Specifically, we evaluated the immunoreactivity of MMPs and TIMPs in various cell types in brain parenchyma and meninges obtained from autopsy tissues. We found that a higher proportion of endothelial cells were positive for MMP-9 during meningitis when compared to controls. In addition, the immunoreactivity of MMP-9 decreased and the immunoreactivity of TIMP-1 increased in astrocytes upon infection. Furthermore, the results of this study revealed that mononuclear cells were highly immunoreactive for TIMP-1, TIMP-2 and MMP-9 during viral meningitis and that the expression of TIMPs in polymorphonuclear cells was even higher during bacterial meningitis. Taken together the results of this study indicated that the central nervous system resident cells and inflammatory infiltrates contribute to MMPs activity and that the expression patterns vary between cell types and in response to viral and bacterial meningitis.

  16. Association between early airway damage-associated molecular patterns and subsequent bacterial infection in patients with inhalational and burn injury.

    Science.gov (United States)

    Maile, Robert; Jones, Samuel; Pan, Yinghao; Zhou, Haibo; Jaspers, Ilona; Peden, David B; Cairns, Bruce A; Noah, Terry L

    2015-05-01

    Bacterial infection is a major cause of morbidity affecting outcome following burn and inhalation injury. While experimental burn and inhalation injury animal models have suggested that mediators of cell damage and inflammation increase the risk of infection, few studies have been done on humans. This is a prospective, observational study of patients admitted to the North Carolina Jaycee Burn Center at the University of North Carolina who were intubated and on mechanical ventilation for treatment of burn and inhalational injury. Subjects were enrolled over a 2-yr period and followed till discharge or death. Serial bronchial washings from clinically indicated bronchoscopies were collected and analyzed for markers of tissue injury and inflammation. These include damage-associated molecular patterns (DAMPs) such as hyaluronic acid (HA), double-stranded DNA (dsDNA), heat-shock protein 70 (HSP-70), and high-mobility group protein B-1 (HMGB-1). The study population was comprised of 72 patients who had bacterial cultures obtained for clinical indications. Elevated HA, dsDNA, and IL-10 levels in bronchial washings obtained early (the first 72 h after injury) were significantly associated with positive bacterial respiratory cultures obtained during the first 14 days postinjury. Independent of initial inhalation injury severity and extent of surface burn, elevated levels of HA dsDNA and IL-10 in the central airways obtained early after injury are associated with subsequent positive bacterial respiratory cultures in patients intubated after acute burn/inhalation injury.

  17. Liver is the major source of elevated serum lipocalin-2 levels after bacterial infection or partial hepatectomy

    DEFF Research Database (Denmark)

    Xu, Ming-Jiang; Feng, Dechun; Wu, Hailong;

    2015-01-01

    knockout (Lcn2(Hep-/-)) mice were generated and subjected to bacterial infection (with Klesbsiella pneumoniae or Escherichia coli) or partial hepatectomy (PHx). Studies of Lcn2(Hep-/-) mice revealed that hepatocytes contributed to 25% of the low basal serum level of LCN2 protein (∼ 62 ng/mL) but were...... responsible for more than 90% of the highly elevated serum LCN2 protein level (∼ 6,000 ng/mL) postinfection and more than 60% post-PHx (∼ 700 ng/mL). Interestingly, both Lcn2(Hep-/-) and global Lcn2 knockout (Lcn2(-/-)) mice demonstrated comparable increases in susceptibility to infection with K. pneumoniae...

  18. A rapidly progressing, deadly disease of Actias selene (Indianmoonmoth) larvae associated with a mixed bacterial and baculoviral infection

    Indian Academy of Sciences (India)

    Marta A Skowron; Beata Guzow-Krzemińska; Sylwia Barańska; Paulina Jędrak; Grzegorz Węgrzyn

    2015-09-01

    The outbreak of an infectious disease in captive-bred Lepidoptera can cause death of all the caterpillars within days. A mixed baculoviral–bacterial infection observed among Actias selene (Hübner 1807), the Indian moon moth (Insecta: Lepidoptera: Saturniidae), larvae was characterized and followed by a photographic documentation of the disease progression. The etiological agents were determined using mass spectrometry and polymerase chain reaction (PCR). It appeared that the disease was caused by a mixed infection of larvae with a baculovirus and Morganella morganii. A molecular phylogenetic analysis of the virus and microbiological description of the pathogenic bacterium are presented.

  19. Expression of bacterial virulence factors and cytokines during in vitro macrophage infection by enteroinvasive Escherichia coli and Shigella flexneri: a comparative study

    Directory of Open Access Journals (Sweden)

    Silvia Y Bando

    2010-09-01

    Full Text Available Enteroinvasive Escherichia coli (EIEC and Shigellaspp cause bacillary dysentery in humans by invading and multiplying within epithelial cells of the colonic mucosa. Although EIEC and Shigellashare many genetic and biochemical similarities, the illness caused by Shigellais more severe. Thus, genomic and structure-function molecular studies on the biological interactions of these invasive enterobacteria with eukaryotic cells have focused on Shigella rather than EIEC. Here we comparatively studied the interactions of EIEC and of Shigella flexneriwith cultured J774 macrophage-like cells. We evaluated several phenotypes: (i bacterial escape from macrophages after phagocytosis, (ii macrophage death induced by EIEC and S. flexneri, (iii macrophage cytokine expression in response to infection and (iv expression of plasmidial (pINV virulence genes. The results showed thatS. flexneri caused macrophage killing earlier and more intensely than EIEC. Both pathogens induced significant macrophage production of TNF, IL-1 and IL-10 after 7 h of infection. Transcription levels of the gene invasion plasmid antigen-C were lower in EIEC than in S. flexneri throughout the course of the infection; this could explain the diminished virulence of EIEC compared to S. flexneri.

  20. Bacterial Etiology and Antibiotic Resistance Profile of Community-Acquired Urinary Tract Infections in a Cameroonian City

    OpenAIRE

    Rolf Nyah-tuku Nzalie; Hortense Kamga Gonsu; Sinata Koulla-Shiro

    2016-01-01

    Introduction. Community-acquired urinary tract infections (CAUTIs) are usually treated empirically. Geographical variations in etiologic agents and their antibiotic sensitivity patterns are common. Knowledge of antibiotic resistance trends is important for improving evidence-based recommendations for empirical treatment of UTIs. Our aim was to determine the major bacterial etiologies of CAUTIs and their antibiotic resistance patterns in a cosmopolitan area of Cameroon for comparison with pres...

  1. Subgroup J avian leukosis virus infection of chicken dendritic cells induces apoptosis via the aberrant expression of microRNAs.

    Science.gov (United States)

    Liu, Di; Dai, Manman; Zhang, Xu; Cao, Weisheng; Liao, Ming

    2016-02-01

    Subgroup J avian leukosis virus (ALV-J) is an oncogenic retrovirus that causes immunosuppression and enhances susceptibility to secondary infection. The innate immune system is the first line of defense in preventing bacterial and viral infections, and dendritic cells (DCs) play important roles in innate immunity. Because bone marrow is an organ that is susceptible to ALV-J, the virus may influence the generation of bone marrow-derived DCs. In this study, DCs cultured in vitro were used to investigate the effects of ALV infection. The results revealed that ALV-J could infect these cells during the early stages of differentiation, and infection of DCs with ALV-J resulted in apoptosis. miRNA sequencing data of uninfected and infected DCs revealed 122 differentially expressed miRNAs, with 115 demonstrating upregulation after ALV-J infection and the other 7 showing significant downregulation. The miRNAs that exhibited the highest levels of upregulation may suppress nutrient processing and metabolic function. These results indicated that ALV-J infection of chicken DCs could induce apoptosis via aberrant microRNA expression. These results provide a solid foundation for the further study of epigenetic influences on ALV-J-induced immunosuppression.

  2. A peptide antagonist of CD28 signaling attenuates toxic shock and necrotizing soft-tissue infection induced by Streptococcus pyogenes.

    Science.gov (United States)

    Ramachandran, Girish; Tulapurkar, Mohan E; Harris, Kristina M; Arad, Gila; Shirvan, Anat; Shemesh, Ronen; Detolla, Louis J; Benazzi, Cinzia; Opal, Steven M; Kaempfer, Raymond; Cross, Alan S

    2013-06-15

    Staphylococcus aureus and group A Streptococcus pyogenes (GAS) express superantigen (SAg) exotoxin proteins capable of inducing lethal shock. To induce toxicity, SAgs must bind not only to the major histocompatibility complex II molecule of antigen-presenting cells and the variable β chain of the T-cell receptor but also to the dimer interface of the T-cell costimulatory receptor CD28. Here, we show that the CD28-mimetic peptide AB103 (originally designated "p2TA") protects mice from lethal challenge with streptococcal exotoxin A, as well as from lethal GAS bacterial infection in a murine model of necrotizing soft-tissue infection. Administration of a single dose of AB103 increased survival when given up to 5 hours after infection, reduced inflammatory cytokine expression and bacterial burden at the site of infection, and improved muscle inflammation in a dose-dependent manner, without compromising cellular and humoral immunity. Thus, AB103 merits further investigation as a potential therapeutic in SAg-mediated necrotizing soft-tissue infection.

  3. MRI visualization of Staphyloccocus aureus-induced infective endocarditis in mice.

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    Janine Ring

    Full Text Available Infective endocarditis (IE is a severe and often fatal disease, lacking a fast and reliable diagnostic procedure. The purpose of this study was to establish a mouse model of Staphylococcus aureus-induced IE and to develop a MRI technology to characterize and diagnose IE. To establish the mouse model of hematogenous IE, aortic valve damage was induced by placing a permanent catheter into right carotid artery. 24 h after surgery, mice were injected intravenously with either iron particle-labeled or unlabeled S. aureus (strain 6850. To distinguish the effect of IE from mere tissue injury or recruited macrophages, subgroups of mice received sham surgery prior to infection (n = 17, received surgery without infection (n = 8, or obtained additionally injection of free iron particles to label macrophages (n = 17. Cardiac MRI was performed 48 h after surgery using a self-gated ultra-short echo time (UTE sequence (TR/TE, 5/0.31 ms; in-plane/slice, 0.125/1 mm; duration, 12∶08 min to obtain high-resolution, artifact-free cinematographic images of the valves. After MRI, valves were either homogenized and plated on blood agar plates for determination of bacterial titers, or sectioned and stained for histology. In the animal model, both severity of the disease and mortality increased with bacterial numbers. Infection with 105 S. aureus bacteria reliably caused endocarditis with vegetations on the valves. Cinematographic UTE MRI visualised the aortic valve over the cardiac cycle and allowed for detection of bacterial vegetations, while mere tissue trauma or labeled macrophages were not detected. Iron labeling of S. aureus was not required for detection. MRI results were consistent with histology and microbial assessment. These data showed that S. aureus-induced IE in mice can be detected by MRI. The established mouse model allows for investigation of the pathophysiology of IE, testing of novel drugs and may serve for the development of a clinical

  4. Significance of inducible defense-related proteins in infected plants

    NARCIS (Netherlands)

    Loon, L.C. van; Rep, M.; Pieterse, C.M.J.

    2006-01-01

    Inducible defense-related proteins have been described in many plant species upon infection with oomycetes, fungi, bacteria, or viruses, or insect attack. Several types of proteins are common and have been classified into 17 families of pathogenesis-related proteins (PRs). Others have so far been fo

  5. Clinical Evaluation of ERCP and Naobiliary Drainage for Biliary Fungal Infection--A Report of Five Cases of Severe Combined Bacterial and Fungal Infection of Biliary Tract

    Institute of Scientific and Technical Information of China (English)

    ZHAO Qiu; LIAO Jiazhi; QIN Hua; WANG Jialong

    2005-01-01

    This study studied the use of ERCP and nasobiliary tube in the diagnosis of fungal infection of biliary tract and the efficacy of combined use of local administration via nasobiliary tube and intravenous antifungal treatment for severe biliary tract fungal infection. 5 patients in our series,with age ranging from 47 to 68 y (mean 55.8), were diagnosed as having mixed bacterial and fungal infection of biliary tract as confirmed by smear or/and culture of bile obtained by ERCP and nasobiliary drainage. Besides routine anti-bacteria therapy, all patients received local application of fluconazole through nasobiliary tube and intravenous administration of fluconazole or itraconazole in terms of the results of in vitro sensitivity test. The mean duration of intravenous fluconazole or itraconazole was 30 days (24-40 days), and that of local application of fluconazole through nasobiliary drainage tube was 19 days (8-24 days). During a follow-up period of 3-42 months, all patient's fungal infection of biliary tract was cured. It is concluded that on the basis of typical clinical features of biliary tract infection, fungal detection of smear/culture of bile obtained by ERCP was the key for the diagnosis of fungal infection of biliary tract. Local application antifungal drug combined with intravenous anti-fungal drugs might be an effective and safe treatment for fungal infection of biliary tract.

  6. Late steps of parvoviral infection induce changes in cell morphology.

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    Pakkanen, Kirsi; Nykky, Jonna; Vuento, Matti

    2008-11-01

    Previously, virus-induced non-filopodial extensions have not been encountered in connection with viral infections. Here, we report emergence of long extensions protruding from Norden laboratory feline kidney (NLFK) and A72 (canine fibroma) cells infected with canine parvovirus for 72 h. These extensions significantly differ in length and number from those appearing in control cells. The most striking feature in the extensions is the length, reaching up to 130 microm, almost twice the average length of a healthy NLFK cell. In A72 cells, the extensions were even longer, up to 200 microm. The results presented here also suggest that the events leading to the growth of these extensions start earlier in infection and abnormal extension growth is detectable already at 24-h post-infection (p.i.). These extensions may have a vital role in the cell-to-cell transmission of the virus.

  7. IL-17A is produced by Th17, gammadelta T cells and other CD4- lymphocytes during infection with Salmonella enterica serovar Enteritidis and has a mild effect in bacterial clearance.

    Science.gov (United States)

    Schulz, Silke M; Köhler, Gabriele; Holscher, Christoph; Iwakura, Yoichiro; Alber, Gottfried

    2008-09-01

    T(h)17 cells represent a new pro-inflammatory T(h) cell lineage distinct from T(h)1 and T(h)2 cells. T(h)17 cells have been shown to be involved in extracellular bacterial infection but their role in intracellular infection remains unclear. We found antigen-specific IL-17A production during a systemic infection of mice with the facultative intracellular bacterium Salmonella enterica serovar Enteritidis (S. Enteritidis) and examined the function and cellular source of IL-17A during the adaptive immune response to S. Enteritidis. Infected IL-17A-/- mice survived completely after inoculation with the highest infection dose found to be sub-lethal for wild-type (WT) C57BL/6 mice. However, at 20 and 80 days post-infection (d.p.i.), we repeatedly found mildly elevated bacterial burden in spleen and liver of IL-17A-/- mice as compared with WT mice. Overall, IL-17A-/- mice showed reduced clearance of S. Enteritidis. S. Enteritidis-specific IL-17A production was induced in splenocytes and lymph node cells of infected WT mice at both time points, 20 and 80 d.p.i. Classical CD4+ T(h)17 cells developed upon infection with Salmonella. CD4- gammadelta TCR+ and CD4- gammadelta TCR- cells were found to be additional IL-17A-producing cell populations. In infected IL-17A-/- mice, a normal T(h)1 cytokine profile was observed consistent with the overall subtle phenotype. Nevertheless, in the absence of IL-17A, recruitment of neutrophils and delayed-type hypersensitivity (DTH) reactivity was significantly compromised. Our data indicate that IL-17A responses are induced by Salmonella and mildly contribute to protective immunity during S. Enteritidis infection. Thus, IL-17A complements the IL-12/IFN-gamma axis which is essential for protective immunity against salmonellosis in mice and men.

  8. [Profile of bacterial resistance in pediatric urinary tract infections in 2014].

    Science.gov (United States)

    Flammang, A; Morello, R; Vergnaud, M; Brouard, J; Eckart, P

    2017-03-01

    In pediatric units, bacteria-producing extended-spectrum-betalactamase (ESBL) have an increasing prevalence among bacteria causing febrile urinary tract infections (UTIs). The purpose of this study was to evaluate the epidemiology of bacteria resistance patterns observed in UTIs, in order to assess the current antibiotic treatment protocols. This study is based upon a single-center retrospective chart review of the cytobacteriological urine cultures performed in UTIs between 1 January and 31 December 2014, in the medical pediatric unit of the Caen University Hospital. Out of the total of 219 cases of UTI, 26.9% were recurrences of UTI, 18.3% were infections in infants less than 3 months old, 21% of the patients suffered from underlying uropathy, and 16.4% of the patients had recently been exposed to antibiotics. In 80.3% of the cases, Escherichia coli was found, while Enterococcus faecalis was found in 5.6%. The antibiograms proved that 33.5% of the bacteria were sensitive. Half of E. coli were resistant to ampicillin, 4.9% to cefixime, 4.9% to ceftriaxone, 1.1% to gentamicin, and 27.8% to trimethoprim-sulfamethoxazole. Nine E. coli and one Enterobacter cloacae produced ESBL, accounting for 4.6% of the UTIs. We did not find any bacteria-producing high-level cephalosporinase. Cefixime resistance was statistically linked to ongoing antibiotic treatment (OR=5.98; 95% CI [1.44; 24.91], P=0.014) and underlying uropathy (OR=6.24; 95% CI [1.47; 26.42], P=0.013). Ceftriaxone resistance was statistically related to ongoing antibiotic treatment (OR=6.93; 95% CI [1.45; 33.13], P=0.015). These results argue in favor of maintaining intravenous ceftriaxone for probabilistic ambulatory treatment. However, in case of hospitalization, cefotaxime can replace ceftriaxone, due to its lower ecological impact. Moreover, it is necessary to continue monitoring bacterial resistance and regularly review our treatment protocols.

  9. Polymicrobial nature of chronic diabetic foot ulcer biofilm infections determined using bacterial tag encoded FLX amplicon pyrosequencing (bTEFAP.

    Directory of Open Access Journals (Sweden)

    Scot E Dowd

    Full Text Available BACKGROUND: Diabetic extremity ulcers are associated with chronic infections. Such ulcer infections are too often followed by amputation because there is little or no understanding of the ecology of such infections or how to control or eliminate this type of chronic infection. A primary impediment to the healing of chronic wounds is biofilm phenotype infections. Diabetic foot ulcers are the most common, disabling, and costly complications of diabetes. Here we seek to derive a better understanding of the polymicrobial nature of chronic diabetic extremity ulcer infections. METHODS AND FINDINGS: Using a new bacterial tag encoded FLX amplicon pyrosequencing (bTEFAP approach we have evaluated the bacterial diversity of 40 chronic diabetic foot ulcers from different patients. The most prevalent bacterial genus associated with diabetic chronic wounds was Corynebacterium spp. Findings also show that obligate anaerobes including Bacteroides, Peptoniphilus, Fingoldia, Anaerococcus, and Peptostreptococcus spp. are ubiquitous in diabetic ulcers, comprising a significant portion of the wound biofilm communities. Other major components of the bacterial communities included commonly cultured genera such as Streptococcus, Serratia, Staphylococcus and Enterococcus spp. CONCLUSIONS: In this article, we highlight the patterns of population diversity observed in the samples and introduce preliminary evidence to support the concept of functional equivalent pathogroups (FEP. Here we introduce FEP as consortia of genotypically distinct bacteria that symbiotically produce a pathogenic community. According to this hypothesis, individual members of these communities when they occur alone may not cause disease but when they coaggregate or consort together into a FEP the synergistic effect provides the functional equivalence of well-known pathogens, such as Staphylococcus aureus, giving the biofilm community the factors necessary to maintain chronic biofilm infections

  10. Bacterial diversity in shallow oligotrophic marine benthos and overlying waters: effects of virus infection, containment, and nutrient enrichment.

    Science.gov (United States)

    Hewson, I; Vargo, G A; Fuhrman, J A

    2003-10-01

    Little is known of the factors shaping sediment bacterial communities, despite their high abundance and reports of high diversity. Two factors hypothesized to shape bacterial communities in the water column are nutrient (resource) availability and virus infection. The role these factors play in benthic bacterial diversity was assessed in oligotrophic carbonate-based sediments of Florida Bay (USA). Sediment-water mesocosm enclosures were made from 1-m diameter clear polycarbonate cylinders which were pushed into sediments to approximately 201 cm sediment depth enclosing approximately 80 L of water. Mesocosms were amended each day for 14 d with 10 microM NH4+ and 1 microM PO4(3-). In a second experiment, viruses from a benthic flocculent layer were concentrated and added back to flocculent layer samples which were collected near the mesocosm enclosures. Photosynthesis by microalgae in virus-amended incubations was monitored by pulse-amplitude modulated (PAM) fluorescence. In both experiments, bacterial diversity was estimated using automated rRNA intergenic spacer analysis (ARISA), a high-resolution fingerprinting approach. Initial sediment bacterial operational taxonomic unit (OTU) richness (236 +/- 3) was higher than in the water column (148 +/- 9), where an OTU was detectable when its amplified DNA represented >0.09% of the total amplified DNA. Effects on bacterial diversity and operational taxonomic unit (OTU) richness in nutrient-amended mesocosms may have been masked by the effects of containment, which stimulated OTU richness in the water column, but depressed OTU richness and diversity in sediments. Nutrient addition significantly elevated virus abundance and the ratio of viruses to bacteria (p < 0.05 for both) in the sediments, concomitant with elevated bacterial diversity. However, water column bacterial diversity (in unamended controls) was not affected by nutrient amendments, which may be due to rapid nutrient uptake by sediment organisms or adsorption of

  11. Lab-score is a valuable predictor of serious bacterial infection in infants admitted to hospital.

    Science.gov (United States)

    Markic, Josko; Kovacevic, Tanja; Krzelj, Vjekoslav; Bosnjak, Nada; Sapunar, Ada

    2015-12-01

    Parents frequently bring their children to the Emergency Department (ED) because of the fever without apparent source (FWAS). To avoid possible complications, it is important to recognize serious bacterial infection (SBI) as early as possible. Various tests, including different clinical scores and scales, are used in the laboratory evaluation of patients. However, it is still impossible to predict the presence of SBI with complete certainty. Galetto-Lacour et al. developed and validated a risk index score, named Lab-score. Lab-score is based on the three predictive variables independently associated with SBI: procalcitonin (PCT), C-reactive protein (CRP), and urinary dipstick. The objective of this study was to assess the performance of the Lab-score in predicting SBI in well-appearing infants ≤ 180 days of age with FWAS, who presented to ED and were hospitalized with suspicion of having SBI. Based on this study findings, white blood cells count (WBC), CRP, PCT, and lab-score ≥ 3 were confirmed as useful biomarkers for differentiation between SBI and non-SBI. Also, receiver operating characteristic curve (ROC) analysis confirmed that all of them were useful for differentiation between SBI and non-SBI patients with the highest area under curve (AUC) calculated for the Lab-score. The results of this research confirmed its value, with calculated sensitivity of 67.7% and specificity of 98.6% in prediction of SBI in infants aged ≤ 180 days. Its value was even better in infants aged ≤ 90 days with sensitivity of 75% and specificity of 97.7%. In conclusion, we demonstrated the high value of lab-score in detecting SBI in infants under 6 months of age with FWAS.

  12. Impairment of the biomechanical compliance of P pili: a novel means of inhibiting uropathogenic bacterial infections?

    Science.gov (United States)

    Klinth, Jeanna E; Pinkner, Jerome S; Hultgren, Scott J; Almqvist, Fredrik; Uhlin, Bernt Eric; Axner, Ove

    2012-03-01

    Gram-negative bacteria often initiate their colonization by use of extended attachment organelles, so called pili. When exposed to force, the rod of helix-like pili has been found to be highly extendable, mainly attributed to uncoiling and recoiling of its quaternary structure. This provides the bacteria with the ability to redistribute an external force among a multitude of pili, which enables them to withstand strong rinsing flows, which, in turn, facilitates adherence and colonization processes critical to virulence. Thus, pili fibers are possible targets for novel antibacterial agents. By use of a substance that compromises compliance of the pili, the ability of bacteria to redistribute external forces can be impaired, so they will no longer be able to resist strong urine flow and thus be removed from the host. It is possible such a substance can serve as an alternative to existing antibiotics in the future or be a part of a multi-drug. In this work we investigated whether it is possible to achieve this by targeting the recoiling process. The test substance was purified PapD. The effect of PapD on the compliance of P pili was assessed at the single organelle level by use of force-measuring optical tweezers. We showed that the recoiling process, and thus the biomechanical compliance, in particular the recoiling process, can be impaired by the presence of PapD. This leads to a new concept in the search for novel drug candidates combating uropathogenic bacterial infections--"coilicides", targeting the subunits of which the pilus rod is composed.

  13. Biomarker-based classification of bacterial and fungal whole-blood infections in a genome-wide expression study

    Directory of Open Access Journals (Sweden)

    Andreas eDix

    2015-03-01

    Full Text Available Sepsis is a clinical syndrome that can be caused by bacteria or fungi. Early knowledge on the nature of the causative agent is a prerequisite for targeted anti-microbial therapy. Besides currently used detection methods like blood culture and PCR-based assays, the analysis of the transcriptional response of the host to infecting organisms holds great promise. In this study, we aim to examine the transcriptional footprint of infections caused by the bacterial pathogens Staphylococcus aureus and Escherichia coli and the fungal pathogens Candida albicans and Aspergillus fumigatus in a human whole-blood model. Moreover, we use the expression information to build a random forest classifier to classify if a sample contains a bacterial, fungal, or mock-infection. After normalizing the transcription intensities using stably expressed reference genes, we filtered the gene set for biomarkers of bacterial or fungal blood infections. This selection is based on differential expression and an additional gene relevance measure. In this way, we identified 38 biomarker genes, including IL6, SOCS3, and IRG1 which were already associated to sepsis by other studies. Using these genes, we trained the classifier and assessed its performance. It yielded a 96% accuracy (sensitivities >93%, specificities >97% for a 10-fold stratified cross-validation and a 92% accuracy (sensitivities and specificities >83% for an additional test dataset comprising Cryptococcus neoformans infections. Furthermore, the classifier is robust to Gaussian noise, indicating correct class predictions on datasets of new species. In conclusion, this genome-wide approach demonstrates an effective feature selection process in combination with the construction of a well-performing classification model. Further analyses of genes with pathogen-dependent expression patterns can provide insights into the systemic host responses, which may lead to new anti-microbial therapeutic advances.

  14. Organization and Biology of the Porcine Serum Amyloid A (SAA) Gene Cluster: Isoform Specific Responses to Bacterial Infection

    DEFF Research Database (Denmark)

    Olsen, Helle G; Skovgaard, Kerstin; Nielsen, Ole L;

    2013-01-01

    infected with the Gram-positive bacterium Staphylococcus aureus. Our results show that: 1) SAA1 may be a pseudogene in pigs; 2) we were able to detect two previously uncharacterized SAA transcripts, namely SAA2 and SAA4, of which the SAA2 transcript is primarily induced in the liver during acute infection...... weakly in pigs infected with S. aureus. These results for the first time establish the infection response patterns of the four porcine SAA genes which will be of importance for the use of the pig as a model for human inflammatory responses, e.g. within sepsis, cancer, and obesity research....

  15. Corticosteroid-induced immunosuppression ultimately does not compromise the efficacy of antibiotherapy in murine Mycobacterium ulcerans infection.

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    Teresa G Martins

    Full Text Available BACKGROUND: Buruli ulcer (BU is a necrotizing disease of the skin, subcutaneous tissue and bone caused by Mycobacterium ulcerans. It has been suggested that the immune response developed during the recommended rifampicin/streptomycin (RS antibiotherapy is protective, contributing to bacterial clearance. On the other hand, paradoxical reactions have been described during or after antibiotherapy, characterized by pathological inflammatory responses. This exacerbated inflammation could be circumvented by immunosuppressive drugs. Therefore, it is important to clarify if the immune system contributes to bacterial clearance during RS antibiotherapy and if immunosuppression hampers the efficacy of the antibiotic regimen. METHODOLOGY/PRINCIPAL FINDINGS: We used the M. ulcerans infection footpad mouse model. Corticosteroid-induced immunosuppression was achieved before experimental infection and maintained during combined RS antibiotherapy by the administration of dexamethasone (DEX. Time-lapsed analyses of macroscopic lesions, bacterial burdens, histology and immunohistochemistry were performed in M. ulcerans-infected footpads. We show here that corticosteroid-immunosuppressed mice are more susceptible to M. ulcerans, with higher bacterial burdens and earlier ulceration. Despite this, macroscopic lesions remised during combined antibiotic/DEX treatment and no viable bacteria were detected in the footpads after RS administration. This was observed despite a delayed kinetics in bacterial clearance, associated with a local reduction of T cell and neutrophil numbers, when compared with immunocompetent RS-treated mice. In addition, no relapse was observed following an additional 3 month period of DEX administration. CONCLUSIONS/SIGNIFICANCE: These findings reveal a major role of the RS bactericidal activity for the resolution of M. ulcerans experimental infections even during immunosuppression, and support clinical investigation on the potential use of

  16. Procalcitonin and C-reactive protein cannot differentiate bacterial or viral infection in COPD exacerbation requiring emergency department visits

    Directory of Open Access Journals (Sweden)

    Chang CH

    2015-04-01

    Full Text Available Chih-Hao Chang,1 Kuo-Chien Tsao,2,3 Han-Chung Hu,1,4 Chung-Chi Huang,1,4 Kuo-Chin Kao,1,4 Ning-Hung Chen,1,4 Cheng-Ta Yang,1,4 Ying-Huang Tsai,4,5 Meng-Jer Hsieh4,51Department of Pulmonary and Critical Care Medicine, Linkou Chang-Gung Memorial Hospital, Chang-Gung Medical Foundation, Chang-Gung University College of Medicine, Taoyuan, Taiwan; 2Department of Laboratory Medicine, Linkou Chang-Gung Memorial Hospital, Chang-Gung Medical Foundation; 3Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Taoyuan, Taiwan; 4Department of Respiratory Therapy, Chang-Gung University, Taoyuan, Taiwan; 5Department of Pulmonary and Critical Care Medicine, Chiayi Chang-Gung Memorial Hospital, Chang-Gung Medical Foundation, Puzi City, TaiwanBackground: Viral and bacterial infections are the most common causes of chronic obstructive pulmonary disease (COPD exacerbations. Whether serum inflammatory markers can differentiate bacterial from virus infection in patients with COPD exacerbation requiring emergency department (ED visits remains controversial.Methods: Viral culture and polymerase chain reaction (PCR were used to identify the viruses in the oropharynx of patients with COPD exacerbations. The bacteria were identified by the semiquantitative culture of the expectorated sputum. The peripheral blood white blood cell (WBC counts, serum C-reactive protein (CRP, procalcitonin (PCT, and clinical symptoms were compared among patients with different types of infections.Results: Viruses were isolated from 16 (22.2% of the 72 patients enrolled. The most commonly identified viruses were parainfluenza type 3, influenza A, and rhinovirus. A total of 30 (41.7% patients had positive bacterial cultures, with the most commonly found bacteria being Haemophilus influenzae and Haemophilus parainfluenzae. Five patients (6.9% had both positive sputum cultures and virus identification. The WBC, CRP, and PCT levels of the bacteria-positive and bacteria

  17. Francisella tularensis subsp. tularensis induces a unique pulmonary inflammatory response: role of bacterial gene expression in temporal regulation of host defense responses.

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    Kathie-Anne Walters

    Full Text Available Pulmonary exposure to Francisella tularensis is associated with severe lung pathology and a high mortality rate. The lack of induction of classical inflammatory mediators, including IL1-β and TNF-α, during early infection has led to the suggestion that F. tularensis evades detection by host innate immune surveillance and/or actively suppresses inflammation. To gain more insight into the host response to Francisella infection during the acute stage, transcriptomic analysis was performed on lung tissue from mice exposed to virulent (Francisella tularensis ssp tularensis SchuS4. Despite an extensive transcriptional response in the lungs of animals as early as 4 hrs post-exposure, Francisella tularensis was associated with an almost complete lack of induction of immune-related genes during the initial 24 hrs post-exposure. This broad subversion of innate immune responses was particularly evident when compared to the pulmonary inflammatory response induced by other lethal (Yersinia pestis and non-lethal (Legionella pneumophila, Pseudomonas aeruginosa pulmonary infections. However, the unique induction of a subset of inflammation-related genes suggests a role for dysregulation of lymphocyte function and anti-inflammatory pathways in the extreme virulence of Francisella. Subsequent activation of a classical inflammatory response 48 hrs post-exposure was associated with altered abundance of Francisella-specific transcripts, including those associated with bacterial surface components. In summary, virulent Francisella induces a unique pulmonary inflammatory response characterized by temporal regulation of innate immune pathways correlating with altered bacterial gene expression patterns. This study represents the first simultaneous measurement of both host and Francisella transcriptome changes that occur during in vivo infection and identifies potential bacterial virulence factors responsible for regulation of host inflammatory pathways.

  18. Suggested guidelines for using systemic antimicrobials in bacterial skin infections: part 2-- antimicrobial choice, treatment regimens and compliance.

    Science.gov (United States)

    Beco, L; Guaguère, E; Lorente Méndez, C; Noli, C; Nuttall, T; Vroom, M

    2013-02-09

    Systemic antimicrobials are critically important in veterinary healthcare, and resistance is a major concern. Antimicrobial stewardship will be important in maintaining clinical efficacy by reducing the development and spread of antimicrobial resistance. Bacterial skin infections are one of the most common reasons for using systemic antimicrobials in dogs and cats. Appropriate management of these infections is, therefore, crucial in any policy for responsible antimicrobial use. The goals of therapy are to confirm that an infection is present, identify the causative bacteria, select the most appropriate antimicrobial, ensure that the infection is treated correctly, and to identify and manage any underlying conditions. This is the second of two articles that provide evidence-led guidelines to help practitioners address these issues. Part 1 discussed the use of clinical signs, cytology and culture in diagnosis. This article will cover the rationale for topical and systemic antimicrobial therapy, including choice of first-, second- and third-line drugs, the dose, duration of therapy, compliance and identification of underlying predisposing conditions. In addition, there is guidance on cases of therapeutic failure and environmental hygiene. These guidelines will help veterinarians avoid the development and propagation of antimicrobial-resistant bacterial strains.

  19. Bacterial superantigens promote acute nasopharyngeal infection by Streptococcus pyogenes in a human MHC Class II-dependent manner.

    Science.gov (United States)

    Kasper, Katherine J; Zeppa, Joseph J; Wakabayashi, Adrienne T; Xu, Stacey X; Mazzuca, Delfina M; Welch, Ian; Baroja, Miren L; Kotb, Malak; Cairns, Ewa; Cleary, P Patrick; Haeryfar, S M Mansour; McCormick, John K

    2014-05-01

    Establishing the genetic determinants of niche adaptation by microbial pathogens to specific hosts is important for the management and control of infectious disease. Streptococcus pyogenes is a globally prominent human-specific bacterial pathogen that secretes superantigens (SAgs) as 'trademark' virulence factors. SAgs function to force the activation of T lymphocytes through direct binding to lateral surfaces of T cell receptors and class II major histocompatibil