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Sample records for aeruginosa lung infection

  1. Chronic Pseudomonas aeruginosa lung infection in normal and athymic rats

    DEFF Research Database (Denmark)

    Johansen, H K; Espersen, F; Pedersen, S S

    1993-01-01

    We have compared a chronic lung infection with Pseudomonas aeruginosa embedded in alginate beads in normal and athymic rats with an acute infection with free live P. aeruginosa bacteria. The following parameters were observed and described: mortality, macroscopic and microscopic pathologic change...

  2. Bioengineered lysozyme in combination therapies for Pseudomonas aeruginosa lung infections

    Science.gov (United States)

    Griswold, Karl E; Bement, Jenna L; Teneback, Charlotte C; Scanlon, Thomas C; Wargo, Matthew J; Leclair, Laurie W

    2014-01-01

    There is increasing urgency in the battle against drug-resistant bacterial pathogens, and this public health crisis has created a desperate need for novel antimicrobial agents. Recombinant human lysozyme represents one interesting candidate for treating pulmonary infections, but the wild type enzyme is subject to electrostatic mediated inhibition by anionic biopolymers that accumulate in the infected lung. We have redesigned lysozyme’s electrostatic potential field, creating a genetically engineered variant that is less susceptible to polyanion inhibition, yet retains potent bactericidal activity. A recent publication demonstrated that the engineered enzyme outperforms wild type lysozyme in a murine model of Pseudomonas aeruginosa lung infection. Here, we expand upon our initial studies and consider dual therapies that combine lysozymes with an antimicrobial peptide. Consistent with our earlier results, the charge modified lysozyme combination outperformed its wild type counterpart, yielding more than an order-of-magnitude reduction in bacterial burden following treatment with a single dose. PMID:24637705

  3. P. aeruginosa in the paranasal sinuses and transplanted lungs have similar adaptive mutations as isolates from chronically infected CF lungs

    DEFF Research Database (Denmark)

    Ciofu, Oana; Johansen, Helle Krogh; Aanaes, Kasper;

    2013-01-01

    BACKGROUND: Pseudomonas aeruginosa cells are present as biofilms in the paranasal sinuses and the lungs of chronically infected cystic fibrosis (CF) patients. Since different inflammatory responses and selective antibiotic pressures are acting in the sinuses compared with the lungs, we compared......-lung transplantation isolates. RESULTS: The same phenotypes caused by similar mutations and similar gene expression profiles were found in mucoid and non-mucoid isolates from the paranasal sinuses and from the lungs before and after transplantation. CONCLUSION: Bilateral exchange of P. aeruginosa isolates between...... the paranasal sinuses and the lungs occurs in chronically infected patients and extensive sinus surgery before the lung transplantation might prevent infection of the new lung....

  4. Improved outcome of chronic Pseudomonas aeruginosa lung infection is associated with induction of a Th1-dominated cytokine response

    DEFF Research Database (Denmark)

    Moser, C; Jensen, P O; Kobayashi, O;

    2002-01-01

    patients, the lungs of susceptible BALB/c mice were re-infected with P. aeruginosa 14 days after the initial infection. Singly-infected BALB/c mice, as well as non-infected mice, were used as controls. Decreased mortality and milder lung inflammation in re-infected BALB/c mice, as well as a tendency......Repeated challenge with antigen is involved in the pathogenesis of a variety of pulmonary diseases. Patients with cystic fibrosis (CF) experience recurrent pulmonary colonization with Pseudomonas aeruginosa before establishment of chronic lung infection. To mimic recurrent lung infections in CF...... production, in chronic P. aeruginosa lung infection in CF....

  5. Pseudomonas aeruginosa mutations in lasl and rhll quorum sensing systems result in milder chronic lung infection

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    Wu, H.; Song, Z.J.; Givskov, Michael Christian;

    2001-01-01

    To understand the importance of quorum sensing in chronic Pseudomonas aeruginosa lung infection, the in vivo pathogenic effects of the wild-type P aeruginosa PAO1 and its double mutant, PAO1 lasI rhlI, in which the signal-generating parts of the quorum sensing systems are defective were compared....

  6. Role of small colony variants in persistence of Pseudomonas aeruginosa infections in cystic fibrosis lungs

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    Malone JG

    2015-07-01

    Full Text Available Jacob G Malone1,21John Innes Centre, Norwich, UK; 2School of Biological Sciences, University of East Anglia, Norwich, UKAbstract: Pseudomonas aeruginosa is an opportunistic pathogen that predominates during the later stages of cystic fibrosis (CF lung infections. Over many years of chronic lung colonization, P. aeruginosa undergoes extensive adaptation to the lung environment, evolving both toward a persistent, low virulence state and simultaneously diversifying to produce a number of phenotypically distinct morphs. These lung-adapted P. aeruginosa strains include the small colony variants (SCVs, small, autoaggregative isolates that show enhanced biofilm formation, strong attachment to surfaces, and increased production of exopolysaccharides. Their appearance in the sputum of CF patients correlates with increased resistance to antibiotics, poor lung function, and prolonged persistence of infection, increasing their relevance as a subject for clinical investigation. The evolution of SCVs in the CF lung is associated with overproduction of the ubiquitous bacterial signaling molecule cyclic-di-GMP, with increased cyclic-di-GMP levels shown to be responsible for the SCV phenotype in a number of different CF lung isolates. Here, we review the current state of research in clinical P. aeruginosa SCVs. We will discuss the phenotypic characteristics underpinning the SCV morphotype, the clinical implications of lung colonization with SCVs, and the molecular basis and clinical evolution of the SCV phenotype in the CF lung environment.Keywords: small colony variants, cystic fibrosis, cyclic-di-GMP, Pseudomonas aeruginosa, RsmA, antibiotics

  7. Detection of N-acylhomoserine lactones in lung tissues of mice infected with Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Wu, H; Song, Z; Hentzer, Morten

    2000-01-01

    microscopy, GFP-expressing E. coli bacteria could be detected in the lung tissues, indicating production and excretion of AHL molecules in vivo by the infecting P. aeruginosa. AHL signals were detected mainly in lung tissues exhibiting severe pathological changes. These findings support the view...

  8. Loss of Social Behaviours in Populations of Pseudomonas aeruginosa Infecting Lungs of Patients with Cystic Fibrosis

    DEFF Research Database (Denmark)

    Jiricny, Natalie; Molin, Søren; Foster, Kevin

    2014-01-01

    Pseudomonas aeruginosa, is an opportunistic, bacterial pathogen causing persistent and frequently fatal infections of the lung in patients with cystic fibrosis. Isolates from chronic infections differ from laboratory and environmental strains in a range of traits and this is widely interpreted as...

  9. Quorum Sensing and Virulence of Pseudomonas aeruginosa during Lung Infection of Cystic Fibrosis Patients

    DEFF Research Database (Denmark)

    Bjarnsholt, T.; Jensen, P.O.; Jakobsen, T.H.;

    2010-01-01

    from the intermittent strains. Dominating changes are the switch to mucoidity ( alginate overproduction) and loss of epigenetic regulation of virulence such as the Quorum Sensing (QS). To elucidate the dynamics of P. aeruginosa QS systems during long term infection of the CF lung, we have investigated...

  10. In situ growth rates and biofilm development of Pseudomonas aeruginosa populations in chronic lung infections

    DEFF Research Database (Denmark)

    Yang, Lei; Haagensen, Janus Anders Juul; Jelsbak, Lars;

    2008-01-01

    The growth dynamics of bacterial pathogens within infected hosts are a fundamental but poorly understood feature of most infections. We have focused on the in situ distribution and growth characteristics of two prevailing and transmissible Pseudomonas aeruginosa clones that have caused chronic lung...... matrix, whereas nonmucoid variants were present mainly as dispersed cells. To obtain estimates of the growth rates of P. aeruginosa in CF lungs, we used quantitative FISH to indirectly measure growth rates of bacteria in sputum samples (reflecting the in vivo lung conditions). The concentration of r......RNA in bacteria isolated from sputa was measured and correlated with the rRNA contents of the same bacteria growing in vitro at defined rates. The results showed that most cells were actively growing with doubling times of between 100 and 200 min, with some growing even faster. Only a small stationary...

  11. Antibodies against beta-lactamase can improve ceftazidime treatment of lung infection with beta-lactam-resistant Pseudomonas aeruginosa in a rat model of chronic lung infection

    DEFF Research Database (Denmark)

    Ciofu, Oana; Bagge, Niels; Høiby, Niels

    2002-01-01

    To test the hypothesis that antibodies against the chromosomal beta-lactamase of Pseudomonas aeruginosa (a beta ab) might act as beta-lactamase inhibitors in patients with cystic fibrosis and chronic lung infection with P. aeruginosa, we compared in a rat model of chronic lung infection...... the efficacy of treatment with ceftazidime in beta-lactamase-immunized (group I) and non-immunized (group II) rats. Chronic lung infection was established with alginate-embedded P. aeruginosa producing high amounts of beta-lactamase in 133 Lewis rats. Prior to infection, group I (66 rats) was immunized three...... times at 2-week intervals with purified beta-lactamase in incomplete Freund's adjuvant (IFA) and group II (67 rats) received IFA. Ceftazidime treatment was initiated after challenge and continued for 10 days, after which the rats were sacrificed and the lung bacteriology and pathology were analysed. Rat...

  12. Novel experimental Pseudomonas aeruginosa lung infection model mimicking long-term host-pathogen interactions in cystic fibrosis

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    Moser, Claus; van Gennip, Maria; Bjarnsholt, Thomas;

    2009-01-01

    Moser C, van Gennip M, Bjarnsholt T, Jensen PO, Lee B, Hougen HP, Calum H, Ciofu O, Givskov M, Molin S, Hoiby N. Novel experimental Pseudomonas aeruginosa lung infection model mimicking long-term host-pathogen interactions in cystic fibrosis. APMIS 2009; 117: 95-107. The dominant cause of premature...... death in patients suffering from cystic fibrosis (CF) is chronic lung infection with Pseudomonas aeruginosa. The chronic lung infection often lasts for decades with just one clone. However, as a result of inflammation, antibiotic treatment and different niches in the lungs, the clone undergoes...

  13. Relationship of iron and extracellular virulence factors to Pseudomonas aeruginosa lung infections.

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    Sokol, P A; Woods, D E

    1984-08-01

    The iron concentration in the culture medium used to prepare the inocula influenced the virulence of Pseudomonas aeruginosa in a chronic pulmonary infection model in rats. Groups of rats were given transtracheal inocula of agar beads in which were embedded c.10(4) cfu of P. aeruginosa strain PAO and the mutants of strain PAO, Fe5 and Fe18. When strain PAO was grown in low-iron medium before infection, it caused severe parenchymal changes including a dense mononuclear cell infiltration in the alveolar spaces, as well as intra- and peribronchial inflammation. When strain PAO was grown in high-iron medium, the pathological changes in lungs were restricted to intra- and peribronchial inflammation. Strain Fe5, in which the effect of iron on yields of elastase is deregulated, produced similar pathological changes regardless of whether it was grown in low- or high-iron media. All rats infected with strain Fe18, in which the effect of iron on yields of toxin A is deregulated, died within 48 h after infection. These data indicate that the iron concentration of the culture medium can influence the pathogenesis of P. aeruginosa in a chronic respiratory infection. These studies also suggest that the regulation of extracellular virulence factors by iron is important in the determination of P. aeruginosa virulence.

  14. Quorum sensing and virulence of Pseudomonas aeruginosa during lung infection of cystic fibrosis patients.

    Directory of Open Access Journals (Sweden)

    Thomas Bjarnsholt

    Full Text Available Pseudomonas aeruginosa is the predominant microorganism in chronic lung infection of cystic fibrosis patients. The chronic lung infection is preceded by intermittent colonization. When the chronic infection becomes established, it is well accepted that the isolated strains differ phenotypically from the intermittent strains. Dominating changes are the switch to mucoidity (alginate overproduction and loss of epigenetic regulation of virulence such as the Quorum Sensing (QS. To elucidate the dynamics of P. aeruginosa QS systems during long term infection of the CF lung, we have investigated 238 isolates obtained from 152 CF patients at different stages of infection ranging from intermittent to late chronic. Isolates were characterized with regard to QS signal molecules, alginate, rhamnolipid and elastase production and mutant frequency. The genetic basis for change in QS regulation were investigated and identified by sequence analysis of lasR, rhlR, lasI and rhlI. The first QS system to be lost was the one encoded by las system 12 years (median value after the onset of the lung infection with subsequent loss of the rhl encoded system after 17 years (median value shown as deficiencies in production of the 3-oxo-C12-HSL and C4-HSL QS signal molecules respectively. The concomitant development of QS malfunction significantly correlated with the reduced production of rhamnolipids and elastase and with the occurrence of mutations in the regulatory genes lasR and rhlR. Accumulation of mutations in both lasR and rhlR correlated with development of hypermutability. Interestingly, a higher number of mucoid isolates were found to produce C4-HSL signal molecules and rhamnolipids compared to the non-mucoid isolates. As seen from the present data, we can conclude that P. aeruginosa and particularly the mucoid strains do not lose the QS regulation or the ability to produce rhamnolipids until the late stage of the chronic infection.

  15. Improved outcome of chronic Pseudomonas aeruginosa lung infection is associated with induction of a Th1-dominated cytokine response

    DEFF Research Database (Denmark)

    Moser, C; Jensen, P O; Kobayashi, O;

    2002-01-01

    Repeated challenge with antigen is involved in the pathogenesis of a variety of pulmonary diseases. Patients with cystic fibrosis (CF) experience recurrent pulmonary colonization with Pseudomonas aeruginosa before establishment of chronic lung infection. To mimic recurrent lung infections in CF p...

  16. Pseudomonas aeruginosa mutations in lasI and rhlI quorum sensing systems result in milder chronic lung infection

    DEFF Research Database (Denmark)

    Wu, H; Song, Z; Givskov, Michael;

    2001-01-01

    To understand the importance of quorum sensing in chronic Pseudomonas aeruginosa lung infection, the in vivo pathogenic effects of the wild-type P. aeruginosa PAO1 and its double mutant, PAO1 lasI rhlI, in which the signal-generating parts of the quorum sensing systems are defective were compared...... be associated with the production of virulence factors that are controlled by the quorum sensing systems. The conclusion of this study is that functional lasI and rhlI genes of P. aeruginosa PAO1 play a significant role during lung infection....

  17. Chronic Pseudomonas aeruginosa lung infection is more severe in Th2 responding BALB/c mice compared to Th1 responding C3H/HeN mice

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    Moser, C; Johansen, H K; Song, Z;

    1997-01-01

    The chronic Pseudomonas aeruginosa lung infection in cystic fibrosis (CF) is characterized by a pronounced antibody response and microcolonies surrounded by numerous polymorphonuclear neutrophils (PMN). Poor prognosis is correlated with a high antibody response to P. aeruginosa antigens. An anima...

  18. Phenotypes selected during chronic lung infection in cystic fibrosis patients: implications for the treatment of Pseudomonas aeruginosa biofilm infections.

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    Ciofu, Oana; Mandsberg, Lotte F; Wang, Hengzhuang; Høiby, Niels

    2012-07-01

    During chronic lung infection of patients with cystic fibrosis, Pseudomonas aeruginosa can survive for long periods of time under the challenging selective pressure imposed by the immune system and antibiotic treatment as a result of its biofilm mode of growth and adaptive evolution mediated by genetic variation. Mucoidy, hypermutability and acquirement of mutational antibiotic resistance are important adaptive phenotypes that are selected during chronic P. aeruginosa infection. This review dicsusses the role played by these phenotypes for the tolerance of biofilms to antibiotics and show that mucoidy and hypermutability change the architecture of in vitro formed biofilms and lead to increase tolerance to antibiotics. Production of high levels of beta-lactamase impairs penetration of beta-lactam antibiotics due to inactivation of the antibiotic. In conclusion, these data underline the importance of biofilm prevention strategies by early aggressive antibiotic prophylaxis or therapy before phenotypic diversification during chronic lung infection of patients with cystic fibrosis.

  19. Pseudomonas aeruginosa AES-1 exhibits increased virulence gene expression during chronic infection of cystic fibrosis lung.

    Directory of Open Access Journals (Sweden)

    Sharna Naughton

    Full Text Available Pseudomonas aeruginosa, the leading cause of morbidity and mortality in people with cystic fibrosis (CF, adapts for survival in the CF lung through both mutation and gene expression changes. Frequent clonal strains such as the Australian Epidemic Strain-1 (AES-1, have increased ability to establish infection in the CF lung and to superimpose and replace infrequent clonal strains. Little is known about the factors underpinning these properties. Analysis has been hampered by lack of expression array templates containing CF-strain specific genes. We sequenced the genome of an acute infection AES-1 isolate from a CF infant (AES-1R and constructed a non-redundant micro-array (PANarray comprising AES-1R and seven other sequenced P. aeruginosa genomes. The unclosed AES-1R genome comprised 6.254Mbp and contained 6957 putative genes, including 338 not found in the other seven genomes. The PANarray contained 12,543 gene probe spots; comprising 12,147 P. aeruginosa gene probes, 326 quality-control probes and 70 probes for non-P. aeruginosa genes, including phage and plant genes. We grew AES-1R and its isogenic pair AES-1M, taken from the same patient 10.5 years later and not eradicated in the intervening period, in our validated artificial sputum medium (ASMDM and used the PANarray to compare gene expression of both in duplicate. 675 genes were differentially expressed between the isogenic pairs, including upregulation of alginate, biofilm, persistence genes and virulence-related genes such as dihydroorotase, uridylate kinase and cardiolipin synthase, in AES-1M. Non-PAO1 genes upregulated in AES-1M included pathogenesis-related (PAGI-5 genes present in strains PACS2 and PA7, and numerous phage genes. Elucidation of these genes' roles could lead to targeted treatment strategies for chronically infected CF patients.

  20. Diversity of metabolic profiles of cystic fibrosis Pseudomonas aeruginosa during the early stages of lung infection

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    Jørgensen, Karin Meinike; Wassermann, Tina; Johansen, Helle Krogh;

    2015-01-01

    Pseudomonas aeruginosa is the dominant pathogen infecting the airways of cystic fibrosis (CF) patients. During the intermittent colonization phase, P. aeruginosa resembles environmental strains but later evolves to the chronic adapted phenotype characterized by resistance to antibiotics...

  1. Pathogenic effects of biofilm with chronic pseudomonas aeruginosa lung infection in rats

    Institute of Scientific and Technical Information of China (English)

    Ping Yan; Yiqiang Chen; Zhijun Song; Hong Wu; Jinliang Kong; Xuejun Qin

    2008-01-01

    Objective: To establish an animal model of P.aeruginosa biofilm associated with chronic pulmonary infection and investigate the pathogenic effects of biofilm. Methods: Experiments in vitro, measuring the MICS, MBCS of ievofloxacin(LFX), ceftazidime(CAZ) in PAO579 in alginate beads and planktonic PAO579. Rats were challenged with 0.1 ml of PAO579(109CFU/ml) in alginate beads or 0.1 ml of planktonic PAO579(109CFU/ml), 3,7,14 days after challenging, bacteriological, pathological features were observed. Results: The MICS, MBCS of LFX, CAZ in PAO579 in alginate beads were higher than those in planktonic PAO579 in vitro. CFU/lung in alginate beads group was significantly higher than that in planktonic bacteria group(P = 0.002, P =0.004, P = 0.002, respectively); macroscopic lung pathology and the inflammation in alginate beads group were significantly more severe compared to those in planktonic bacteria group in vivo. Conclusion: P.aeruginosa biofilm protected bacterium from killing of antibiotics and might mediate the host immune damage in the lung tissue and made bacterium evade the host immune defense.

  2. Early immune response in susceptible and resistant mice strains with chronic Pseudomonas aeruginosa lung infection determines the type of T-helper cell response

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    Moser, C; Hougen, H P; Song, Z;

    1999-01-01

    Most cystic fibrosis (CF) patients become chronically infected with Pseudomonas aeruginosa in the lungs. The infection is characterized by a pronounced antibody response and a persistant inflammation dominated by polymorphonuclear neutrophils. Moreover a high antibody response correlates with a p...

  3. Evolution and diversification of Pseudomonas aeruginosa in the paranasal sinuses of cystic fibrosis children have implications for chronic lung infection

    DEFF Research Database (Denmark)

    Hansen, Susse Kirkelund; Rau, Martin Holm; Johansen, Helle Krogh

    2012-01-01

    The opportunistic pathogen Pseudomonas aeruginosa is a frequent colonizer of the airways of patients suffering from cystic fibrosis (CF). Depending on early treatment regimens, the colonization will, with high probability, develop into chronic infections sooner or later, and it is important to es...... sinuses potentially constitute a protected niche of adapted clones of P. aeruginosa, which can intermittently seed the lungs and pave the way for subsequent chronic lung infections....... and evolution take place in the sinuses. Importantly, before the onset of chronic lung infection, lineages with mutations conferring a large fitness benefit in CF airways such as mucA and lasR as well as small colony variants and antibiotic-resistant clones are part of the sinus populations. Thus, the paranasal...

  4. Vaccines for preventing infection with Pseudomonas aeruginosa in cystic fibrosis

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    Johansen, Helle Krogh; Gøtzsche, Peter C

    2013-01-01

    Chronic pulmonary infection in cystic fibrosis results in progressive lung damage. Once colonisation of the lungs with Pseudomonas aeruginosa occurs, it is almost impossible to eradicate. Vaccines, aimed at reducing infection with Pseudomonas aeruginosa, have been developed.......Chronic pulmonary infection in cystic fibrosis results in progressive lung damage. Once colonisation of the lungs with Pseudomonas aeruginosa occurs, it is almost impossible to eradicate. Vaccines, aimed at reducing infection with Pseudomonas aeruginosa, have been developed....

  5. Pseudomonas aeruginosa Exploits Lipid A and Muropeptides Modification as a Strategy to Lower Innate Immunity during Cystic Fibrosis Lung Infection

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    Ieranò, Teresa; Lorè, Nicola Ivan; Bianconi, Irene; Silipo, Alba; Cozzolino, Flora; Lanzetta, Rosa; Molinaro, Antonio; Bernardini, Maria Lina; Bragonzi, Alessandra

    2009-01-01

    Pseudomonas aeruginosa can establish life-long airways chronic infection in patients with cystic fibrosis (CF) with pathogenic variants distinguished from initially acquired strain. Here, we analysed chemical and biological activity of P. aeruginosa Pathogen-Associated Molecular Patterns (PAMPs) in clonal strains, including mucoid and non-mucoid phenotypes, isolated during a period of up to 7.5 years from a CF patient. Chemical structure by MS spectrometry defined lipopolysaccharide (LPS) lipid A and peptidoglycan (PGN) muropeptides with specific structural modifications temporally associated with CF lung infection. Gene sequence analysis revealed novel mutation in pagL, which supported lipid A changes. Both LPS and PGN had different potencies when activating host innate immunity via binding TLR4 and Nod1. Significantly higher NF-kB activation, IL-8 expression and production were detected in HEK293hTLR4/MD2-CD14 and HEK293hNod1 after stimulation with LPS and PGN respectively, purified from early P. aeruginosa strain as compared to late strains. Similar results were obtained in macrophages-like cells THP-1, epithelial cells of CF origin IB3-1 and their isogenic cells C38, corrected by insertion of cystic fibrosis transmembrane conductance regulator (CFTR). In murine model, altered LPS structure of P. aeruginosa late strains induces lower leukocyte recruitment in bronchoalveolar lavage and MIP-2, KC and IL-1β cytokine levels in lung homogenates when compared with early strain. Histopathological analysis of lung tissue sections confirmed differences between LPS from early and late P. aeruginosa. Finally, in this study for the first time we unveil how P. aeruginosa has evolved the capacity to evade immune system detection, thus promoting survival and establishing favourable conditions for chronic persistence. Our findings provide relevant information with respect to chronic infections in CF. PMID:20037649

  6. Novel mouse model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis

    DEFF Research Database (Denmark)

    Hoffmann, Nadine; Rasmussen, Thomas Bovbjerg; Jensen, Peter Østrup

    2005-01-01

    mice (Cftr(tmlUnc-/-)) and BALB/c mice, as reflected by the detection of a high number of P. aeruginosa organisms in the lung homogenates at 7 days postinfection and alginate biofilms, surrounded by polymorphonuclear leukocytes in the alveoli. In comparison, both an AHL-producing nonmucoid revertant...

  7. In situ growth rates and biofilm development of Pseudomonas aeruginosa populations in chronic lung infections

    DEFF Research Database (Denmark)

    Yang, L.; Haagensen, J.A.; Jelsbak, L.

    2008-01-01

    The growth dynamics of bacterial pathogens within infected hosts are a fundamental but poorly understood feature of most infections. We have focused on the in situ distribution and growth characteristics of two prevailing and transmissible Pseudomonas aeruginosa clones that have caused chronic lu...

  8. Protection against Pseudomonas aeruginosa lung infection in mice by recombinant OprF-pulsed dendritic cell immunization

    Directory of Open Access Journals (Sweden)

    De Luna Loredana

    2010-01-01

    Full Text Available Abstract Background The Pseudomonas aeruginosa major constitutive outer membrane porin protein F (OprF has been shown to be a protective antigen and was previously used to activate an immunological response in a mouse model of lung pneumonia. The purpose of our study was to demonstrate the ability of mouse dendritic cells pulsed with purified or recombinant OprF to protect mice against P. aeruginosa infection and inflammation. Both native (n-OprF, isolated and purified from PAO1 bacterial strain, and recombinant (histidin-conjugated OprF (His-OprF, obtained by cloning of the oprF gene into the pET28a expression vector, were used to stimulate dendritic cells in vitro before adoptive transfer into prospective recipient mice with P. aeruginosa pulmonary infection. Results Similar to n-OprF, His-OprF activated dendritic cells in vitro, inducing the costimulatory molecule expression as well as cytokine production. Upon adoptive transfer in vivo, porin-pulsed dendritic cells (DCs induced Th1-mediated resistance to infection and associated inflammatory pathology caused by either the PAO1 strain or a clinically-isolated mucoid strain. Conclusions This study highlights the pivotal contribution of DCs to vaccine-induced protection against P. aeruginosa infection and associated inflammation.

  9. Effect of aquo-alchoholic extract of Glycyrrhiza glabra against Pseudomonas aeruginosa in Mice Lung Infection Model.

    Science.gov (United States)

    Chakotiya, Ankita Singh; Tanwar, Ankit; Srivastava, Pranay; Narula, Alka; Sharma, Rakesh Kumar

    2017-03-26

    The prevalence of lung infection caused by Pseudomonas aeruginosa strains that are classified as multi-drug resistant has increased considerably and is mainly attributed to relative insufficiency of potent chemotherapeutic modalities. The present study was conducted to evaluate the antimicrobial activity of aquo-alcoholic extract of Glycyrrhiza glabra against the P. aeruginosa causing lung infection in Swiss albino mice. The study involves evaluation of lethal dose of P. aeruginosa in Swiss albino mice and analysis of disease manifestation that includes bacteremia, hypothermia, reduction in body weight and other parameters for 48h of infection. Physical manifestations of infected mice showed a significant decline in body temperature that is 29±0.57°C (at 48th h) from 38.81±0.33°C (0h) and 30% weight loss was observed at the end of the study. Further the efficacy of G. glabra extract against lung infection induced with the calculated lethal dose was evaluated by employing bacteremia, histopathology and radiological analysis. Bacterial burden showed that 2.30±0.02 Log10CFU/mL at day 7, a significant decline in the bacterial load as compared to day 1 when the bacterial burden was found to be 3.32±0.1 Log10CFU/mL. Histopathological results showed more diffuse and patchy accumulation of inflammatory cells within the alveolar space also the infiltrates were noted in all the lung section of infected mice. In treated animal group improved lung histology was seen with the exudates were less seen in D1 dose (20mg/kg) and disappeared in D2 dose (80mg/kg). The study clearly declares that the G. glabra extract is effective against lung infection caused by P. aeruginosa at dose of 80mg/kg. The LCMS results revealed that the extract contains Glycyrrhizin, Stigmasterol and Ergosterol, Licochalcone and Glabridin. The current study expected to further exploit the biomedical properties of this extract in the preparation of a potent regimen against such threatening pathogen.

  10. Poor antioxidant status exacerbates oxidative stress and inflammatory response to Pseudomonas aeruginosa lung infection in Guinea Pigs

    DEFF Research Database (Denmark)

    Jensen, Peter Østrup; Lykkesfeldt, Jens; Bjarnsholt, Thomas

    2012-01-01

    , which is the main cause of morbidity and mortality in CF. Guinea pigs are unable to synthesize ascorbate (ASC) or vitamin C, a major antioxidant of the lung, and thus like human beings rely on its presence in the diet. On this basis, guinea pigs receiving ASC-deficient diet have been used as a model...... of oxidative stress. The aim of our study was to investigate the consequences of a 7-day biofilm-grown P. aeruginosa lung infection in 3-month-old guinea pigs receiving either ASC-sufficient or ASC-deficient diet for at least 2 months. The animals receiving ASC-deficient diet showed significantly higher...

  11. Requirement of the Pseudomonas aeruginosa CbrA sensor kinase for full virulence in a murine acute lung infection model.

    Science.gov (United States)

    Yeung, Amy T Y; Janot, Laure; Pena, Olga M; Neidig, Anke; Kukavica-Ibrulj, Irena; Hilchie, Ashley; Levesque, Roger C; Overhage, Joerg; Hancock, Robert E W

    2014-03-01

    Pseudomonas aeruginosa is an opportunistic pathogen that is a major cause of respiratory tract and other nosocomial infections. The sensor kinase CbrA is a central regulator of carbon and nitrogen metabolism and in vitro also regulates virulence-related processes in P. aeruginosa. Here, we investigated the role of CbrA in two murine models of infection. In both peritoneal infections in leukopenic mice and lung infection models, the cbrA mutant was less virulent since substantially larger numbers of cbrA mutant bacteria were required to cause the same level of infection as wild-type or complemented bacteria. In contrast, in the chronic rat lung model the cbrA mutant grew and persisted as well as the wild type, indicating that the decrease of in vivo virulence of the cbrA mutant did not result from growth deficiencies on particular carbon substrates observed in vitro. In addition, a mutant in the cognate response regulator CbrB showed no defect in virulence in the peritoneal infection model, ruling out the involvement of certain alterations of virulence properties in the cbrA mutant including defective swarming motility, increased biofilm formation, and cytotoxicity, since these alterations are controlled through CbrB. Further investigations indicated that the mutant was more susceptible to uptake by phagocytes in vitro, resulting in greater overall bacterial killing. Consistent with the virulence defect, it took a smaller number of Dictyostelium discoideum amoebae to kill the cbrA mutant than to kill the wild type. Transcriptional analysis of the cbrA mutant during D. discoideum infection led to the conclusion that CbrA played an important role in the iron metabolism, protection of P. aeruginosa against oxidative stress, and the regulation of certain virulence factors.

  12. Requirement of the Pseudomonas aeruginosa CbrA Sensor Kinase for Full Virulence in a Murine Acute Lung Infection Model

    Science.gov (United States)

    Yeung, Amy T. Y.; Janot, Laure; Pena, Olga M.; Neidig, Anke; Kukavica-Ibrulj, Irena; Hilchie, Ashley; Levesque, Roger C.; Overhage, Joerg

    2014-01-01

    Pseudomonas aeruginosa is an opportunistic pathogen that is a major cause of respiratory tract and other nosocomial infections. The sensor kinase CbrA is a central regulator of carbon and nitrogen metabolism and in vitro also regulates virulence-related processes in P. aeruginosa. Here, we investigated the role of CbrA in two murine models of infection. In both peritoneal infections in leukopenic mice and lung infection models, the cbrA mutant was less virulent since substantially larger numbers of cbrA mutant bacteria were required to cause the same level of infection as wild-type or complemented bacteria. In contrast, in the chronic rat lung model the cbrA mutant grew and persisted as well as the wild type, indicating that the decrease of in vivo virulence of the cbrA mutant did not result from growth deficiencies on particular carbon substrates observed in vitro. In addition, a mutant in the cognate response regulator CbrB showed no defect in virulence in the peritoneal infection model, ruling out the involvement of certain alterations of virulence properties in the cbrA mutant including defective swarming motility, increased biofilm formation, and cytotoxicity, since these alterations are controlled through CbrB. Further investigations indicated that the mutant was more susceptible to uptake by phagocytes in vitro, resulting in greater overall bacterial killing. Consistent with the virulence defect, it took a smaller number of Dictyostelium discoideum amoebae to kill the cbrA mutant than to kill the wild type. Transcriptional analysis of the cbrA mutant during D. discoideum infection led to the conclusion that CbrA played an important role in the iron metabolism, protection of P. aeruginosa against oxidative stress, and the regulation of certain virulence factors. PMID:24379284

  13. Chronic lung infection by Pseudomonas aeruginosa biofilm is cured by L-Methionine in combination with antibiotic therapy.

    Science.gov (United States)

    Gnanadhas, Divya Prakash; Elango, Monalisha; Datey, Akshay; Chakravortty, Dipshikha

    2015-11-02

    Bacterial biofilms are associated with 80-90% of infections. Within the biofilm, bacteria are refractile to antibiotics, requiring concentrations >1,000 times the minimum inhibitory concentration. Proteins, carbohydrates and DNA are the major components of biofilm matrix. Pseudomonas aeruginosa (PA) biofilms, which are majorly associated with chronic lung infection, contain extracellular DNA (eDNA) as a major component. Herein, we report for the first time that L-Methionine (L-Met) at 0.5 μM inhibits Pseudomonas aeruginosa (PA) biofilm formation and disassembles established PA biofilm by inducing DNase expression. Four DNase genes (sbcB, endA, eddB and recJ) were highly up-regulated upon L-Met treatment along with increased DNase activity in the culture supernatant. Since eDNA plays a major role in establishing and maintaining the PA biofilm, DNase activity is effective in disrupting the biofilm. Upon treatment with L-Met, the otherwise recalcitrant PA biofilm now shows susceptibility to ciprofloxacin. This was reflected in vivo, in the murine chronic PA lung infection model. Mice treated with L-Met responded better to antibiotic treatment, leading to enhanced survival as compared to mice treated with ciprofloxacin alone. These results clearly demonstrate that L-Met can be used along with antibiotic as an effective therapeutic against chronic PA biofilm infection.

  14. Bead-size directed distribution of Pseudomonas aeruginosa results in distinct inflammatory response in a mouse model of chronic lung infection

    DEFF Research Database (Denmark)

    Christophersen, L J; Trøstrup, H; Damlund, Dina Silke Malling;

    2012-01-01

    Chronic Pseudomonas aeruginosa lung infection in cystic fibrosis (CF) patients is characterized by biofilms, tolerant to antibiotics and host responses. Instead, immune responses contribute to the tissue damage. However, this may depend on localization of infection in the upper conductive or in t...

  15. A novel mouse model of conditional IRAK-M deficiency in myeloid cells: application in lung Pseudomonas aeruginosa infection.

    Science.gov (United States)

    Jiang, Di; Matsuda, Jennifer; Berman, Reena; Schaefer, Niccolette; Stevenson, Connor; Gross, James; Zhang, Bicheng; Sanchez, Amelia; Li, Liwu; Chu, Hong Wei

    2017-02-01

    Myeloid cells such as macrophages are critical to innate defense against infection. IL-1 receptor-associated kinase M (IRAK-M) is a negative regulator of TLR signaling during bacterial infection, but the role of myeloid cell IRAK-M in bacterial infection is unclear. Our goal was to generate a novel conditional knockout mouse model to define the role of myeloid cell IRAK-M during bacterial infection. Myeloid cell-specific IRAK-M knockout mice were generated by crossing IRAK-M floxed mice with LysM-Cre knock-in mice. The resulting LysM-Cre(+)/IRAK-M(fl/wt) and control (LysM-Cre(-)/IRAK-M(fl/wt)) mice were intranasally infected with Pseudomonas aeruginosa (PA). IRAK-M deletion, inflammation, myeloperoxidase (MPO) activity and PA load were measured in leukocytes, bronchoalveolar lavage (BAL) fluid and lungs. PA killing assay with BAL fluid was performed to determine mechanisms of IRAK-M-mediated host defense. IRAK-M mRNA and protein levels in alveolar and lung macrophages were significantly reduced in LysM-Cre(+)/IRAK-M(fl/wt) mice compared with control mice. Following PA infection, LysM-Cre(+)/IRAK-M(fl/wt) mice have enhanced lung neutrophilic inflammation, including MPO activity, but reduced PA load. The increased lung MPO activity in LysM-Cre(+)/IRAK-M(fl/wt) mouse BAL fluid reduced PA load. Generation of IRAK-M conditional knockout mice will enable investigators to determine precisely the function of IRAK-M in myeloid cells and other types of cells during infection and inflammation.

  16. Azithromycin blocks quorum sensing and alginate polymer formation and increases the sensitivity to serum and stationary growth phase killing of P. aeruginosa and attenuates chronic P. aeruginosa lung infection in Cftr -/--mice

    DEFF Research Database (Denmark)

    Hoffmann, N.; Lee, Bao le ri; Hentzer, Morten

    2007-01-01

    The consequences of O-acetylated alginate-producing Pseudomonas aeruginosa biofilms in the lungs of chronically infected cystic fibrosis (CF) patients are tolerance to both antibiotic treatments and effects on the innate and the adaptive defense mechanisms. In clinical trials, azithromycin (AZM) ...

  17. Comparative genomics of isolates of a Pseudomonas aeruginosa epidemic strain associated with chronic lung infections of cystic fibrosis patients.

    Directory of Open Access Journals (Sweden)

    Julie Jeukens

    Full Text Available Pseudomonas aeruginosa is the main cause of fatal chronic lung infections among individuals suffering from cystic fibrosis (CF. During the past 15 years, particularly aggressive strains transmitted among CF patients have been identified, initially in Europe and more recently in Canada. The aim of this study was to generate high-quality genome sequences for 7 isolates of the Liverpool epidemic strain (LES from the United Kingdom and Canada representing different virulence characteristics in order to: (1 associate comparative genomics results with virulence factor variability and (2 identify genomic and/or phenotypic divergence between the two geographical locations. We performed phenotypic characterization of pyoverdine, pyocyanin, motility, biofilm formation, and proteolytic activity. We also assessed the degree of virulence using the Dictyostelium discoideum amoeba model. Comparative genomics analysis revealed at least one large deletion (40-50 kb in 6 out of the 7 isolates compared to the reference genome of LESB58. These deletions correspond to prophages, which are known to increase the competitiveness of LESB58 in chronic lung infection. We also identified 308 non-synonymous polymorphisms, of which 28 were associated with virulence determinants and 52 with regulatory proteins. At the phenotypic level, isolates showed extensive variability in production of pyocyanin, pyoverdine, proteases and biofilm as well as in swimming motility, while being predominantly avirulent in the amoeba model. Isolates from the two continents were phylogenetically and phenotypically undistinguishable. Most regulatory mutations were isolate-specific and 29% of them were predicted to have high functional impact. Therefore, polymorphism in regulatory genes is likely to be an important basis for phenotypic diversity among LES isolates, which in turn might contribute to this strain's adaptability to varying conditions in the CF lung.

  18. Lung infection

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008050 The establishment of a rat model of chronic pulmonary infection of Pseudomonas aeruginosa. WANG Weifang(王炜芳), et al. Dept Respir, PLA General Hosp, Beijing 100853. Natl Med J China 2008;88(1):46-50. Objective To establish a rat model of chronic pulmonary infection by inoculating two different Pseudomonas aeruginosa embedded in minute seaweed algiante beads made by an ejection set with an acuminate hole to

  19. Pseudomonas aeruginosa biofilm infections

    DEFF Research Database (Denmark)

    Tolker-Nielsen, Tim

    2014-01-01

    Bacteria in natural, industrial and clinical settings predominantly live in biofilms, i.e., sessile structured microbial communities encased in self-produced extracellular matrix material. One of the most important characteristics of microbial biofilms is that the resident bacteria display...... a remarkable increased tolerance toward antimicrobial attack. Biofilms formed by opportunistic pathogenic bacteria are involved in devastating persistent medical device-associated infections, and chronic infections in individuals who are immune-compromised or otherwise impaired in the host defense. Because...... the use of conventional antimicrobial compounds in many cases cannot eradicate biofilms, there is an urgent need to develop alternative measures to combat biofilm infections. The present review is focussed on the important opportunistic pathogen and biofilm model organism Pseudomonas aeruginosa. Initially...

  20. Pseudomonas aeruginosa chromosomal beta-lactamase in patients with cystic fibrosis and chronic lung infection. Mechanism of antibiotic resistance and target of the humoral immune response

    DEFF Research Database (Denmark)

    Ciofu, Oana

    2003-01-01

    of this therapeutic strategy and our results showed the development of resistance of P. aeruginosa to several antibiotics during 25 years of intensive antibiotic treatment. Our studies have been concentrating on the development of resistance to beta-lactam antibiotics. We have shown an association between...... the development of resistance to beta-lactam antibiotics and the occurrence of high beta-lactamase producing strains and between the MIC of the beta-lactams and the levels of beta-lactamase expression. Partially derepressed mutants, characterized by high basal levels of beta-lactamase with the possibility...... of induction to even higher levels during treatment with beta-lactam antibiotics, were the most frequent phenotype found among resistant Danish P. aeruginosa CF isolates. We have also shown that the high alginate producing P. aeruginosa isolates, that characterize the chronic lung infection in CF patients...

  1. Production of N-acyl-L-homoserine lactones by P. aeruginosa isolates from chronic lung infections associated with cystic fibrosis

    DEFF Research Database (Denmark)

    Geisenberger, O; Givskov, M; Riedel, K;

    2000-01-01

    The N-acyl-L-homoserine lactones (AHLs) produced by sequential Pseudomonas aeruginosa isolates from chronically infected patients with cystic fibrosis were analyzed by thin-layer chromatography. It is demonstrated that both the amounts and the types of molecules synthesized by isolates from...

  2. Faster activation of polymorphonuclear neutrophils in resistant mice during early innate response to Pseudomonas aeruginosa lung infection

    DEFF Research Database (Denmark)

    Jensen, P Ø; Moser, C; Kobayashi, O;

    2004-01-01

    challenge with alginate embedded P. aeruginosa. These parameters were correlated with the quantitative bacteriology and histopathology of the lungs. After challenge, the content of granulocyte colony-stimulating factor (G-CSF) and macrophage inflammatory protein-2 (MIP-2) was increased in the lungs...... was decreased 1 day after bacterial challenge, whereas the expression was increased after 2 days of challenge on PMNs of C3H/HeN mice only. These changes were accompanied by a more severe lung inflammation in BALB/c mice and faster clearance of the bacteria in C3H/HeN mice. In conclusion, the rapid early...... bacterial clearance in the lungs of C3H/HeN mice could be explained by faster activation of the PMNs, as indicated by the higher up-regulation of CD11b. The severe lung inflammation in BALB/c mice may be caused by the early higher content of G-CSF in the sera mobilizing PMNs from the bone marrow...

  3. Activation of pulmonary and lymph node dendritic cells during chronic Pseudomonas aeruginosa lung infection in mice

    DEFF Research Database (Denmark)

    Damlund, Dina S. M.; Christophersen, Lars; Jensen, Peter Østrup

    2016-01-01

    with the adaptive immune response. Once activated, the DCs deliver a set of signals to uncommitted T cells that induce development, such as expansion of regulatory T cells and polarization of Th1, Th2 or Th17 subsets. In this study, we characterized DCs in lungs and regional lymph nodes in BALB/c mice infected...

  4. BIIL 284 reduces neutrophils numbers but increases P. aeruginosa bacteraemia and inflammation in mouse lungs

    Science.gov (United States)

    Döring, Gerd; Bragonzi, Alessandra; Paroni, Moira; Aktürk, Firdevs-Fatma; Cigana, Cristina; Schmidt, Annika; Gilpin, Deirdre; Heyder, Susanne; Born, Torsten; Smaczny, Christina; Kohlhäufl, Martin; Wagner, Thomas O. F.; Loebinger, Michael R.; Bilton, Diana; Tunney, Michael M.; Elborn, J. Stuart; Pier, Gerald B.; Konstan, Michael W.; Ulrich, Martina

    2014-01-01

    Background A clinical study to investigate the leukotriene B4 (LTB4)-receptor antagonist BIIL 284 in cystic fibrosis (CF) patients was prematurely terminated due to a significantly increased risk of adverse pulmonary events. We aimed to establish the effect of BIIL284 in models of Pseudomonas aeruginosa lung infection, thereby contributing to a better understanding of what could have led to adverse pulmonary events in CF patients. Methods P. aeruginosa DNA in the blood of CF patients during and after acute pulmonary exacerbations and in stable patients with non-CF bronchiectasis (NCFB) and healthy individuals was assessed by PCR. The effect of BIIL 284 treatment was tested in an agar beads murine model of Pseudomonas aeruginosa lung infection. Bacterial count and inflammation were evaluated in lung and other organs. Result Most CF patients (98%) and all patients with NCFB and healthy individuals had negative P. aeruginosa DNA in their blood. Similarly, the P. aeruginosa-infected mice showed bacterial counts in the lung but not blood or spleen. BIIL 284 treatment decreased pulmonary neutrophils and increased P. aeruginosa numbers in mouse lungs leading to significantly higher bacteremia rates and lung inflammation compared to placebo treated animals. Conclusions Decreased airway neutrophils induced lung proliferation and severe bacteraemia in a murine model of P. aeruginosa lung infection. These data suggest that caution should be taken when administering anti-inflammatory compounds to patients with bacterial infections. PMID:24183915

  5. Clonal dissemination, emergence of mutator lineages and antibiotic resistance evolution in Pseudomonas aeruginosa cystic fibrosis chronic lung infection.

    Directory of Open Access Journals (Sweden)

    Carla López-Causapé

    Full Text Available Chronic respiratory infection by Pseudomonas aeruginosa is a major cause of mortality in cystic fibrosis (CF. We investigated the interplay between three key microbiological aspects of these infections: the occurrence of transmissible and persistent strains, the emergence of variants with enhanced mutation rates (mutators and the evolution of antibiotic resistance. For this purpose, 10 sequential isolates, covering up to an 8-year period, from each of 10 CF patients were studied. As anticipated, resistance significantly accumulated overtime, and occurred more frequently among mutator variants detected in 6 of the patients. Nevertheless, highest resistance was documented for the nonmutator CF epidemic strain LES-1 (ST-146 detected for the first time in Spain. A correlation between resistance profiles and resistance mechanisms evaluated [efflux pump (mexB, mexD, mexF, and mexY and ampC overexpression and OprD production] was not always obvious and hypersusceptibility to certain antibiotics (such as aztreonam or meropenem was frequently observed. The analysis of whole genome macrorestriction fragments through Pulsed-Field Gel Electrophoresis (PFGE revealed that a single genotype (clone FQSE-A produced persistent infections in 4 of the patients. Multilocus Sequence typing (MLST identified clone FQSE-A as the CF epidemic clone ST-274, but striking discrepancies between PFGE and MLST profiles were evidenced. While PFGE macrorestriction patterns remained stable, a new sequence type (ST-1089 was detected in two of the patients, differing from ST-274 by only two point mutations in two of the genes, each leading to a nonpreviously described allele. Moreover, detailed genetic analyses revealed that the new ST-1089 is a mutS deficient mutator lineage that evolved from the epidemic strain ST-274, acquired specific resistance mechanisms, and underwent further interpatient spread. Thus, presented results provide the first evidence of interpatient dissemination

  6. Nitrous oxide production in sputum from cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infection

    DEFF Research Database (Denmark)

    Kolpen, Mette; Kühl, Michael; Bjarnsholt, Thomas;

    2014-01-01

    .8 µM N2O (range 1.4-157.9 µM N2O). The concentration of N2O in the sputum was higher below the oxygenated layers. In 4 samples the N2O concentration increased during the initial 6 h of measurements before decreasing for approximately 6 h. Concomitantly, the concentration of NO3(-) decreased in sputum...... in the denitrification pathway. We measured N2O and O2 with electrochemical microsensors in 8 freshly expectorated sputum samples from 7 CF patients with chronic P. aeruginosa infection. The concentrations of NO3(-) and NO2(-) in sputum were estimated by the Griess reagent. We found a maximum median concentration of 41...

  7. Garlic blocks quorum sensing and promotes rapid clearing of pulmonary Pseudomonas aeruginosa infections

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas; Jensen, Peter Østrup; Rasmussen, Thomas B;

    2005-01-01

    The opportunistic human pathogen Pseudomonas aeruginosa is the predominant micro-organism of chronic lung infections in cystic fibrosis patients. P. aeruginosa colonizes the lungs by forming biofilm microcolonies throughout the lung. Quorum sensing (QS) renders the biofilm bacteria highly tolerant...

  8. Vaccines for preventing infection with Pseudomonas aeruginosa in cystic fibrosis

    DEFF Research Database (Denmark)

    Johansen, H.K.; Gøtzsche, Peter C.; Johansen, Helle Krogh

    2008-01-01

    BACKGROUND: Chronic pulmonary infection in cystic fibrosis results in progressive lung damage. Once colonisation of the lungs with Pseudomonas aeruginosa occurs, it is almost impossible to eradicate. Vaccines, aimed at reducing infection with Pseudomonas aeruginosa, have been developed. OBJECTIVES......: To assess the effectiveness of vaccination against Pseudomonas aeruginosa in cystic fibrosis. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register using the terms vaccines AND pseudomonas (last search May 2008) and PubMed using the terms vaccin* AND cystic...... fibrosis (last search May 2008). SELECTION CRITERIA: Randomised trials (published or unpublished) comparing Pseudomonas aeruginosa vaccines (oral, parenteral or intranasal) with control vaccines or no intervention in cystic fibrosis. DATA COLLECTION AND ANALYSIS: The authors independently selected trials...

  9. Pseudomonas aeruginosa Biofilm Infections

    DEFF Research Database (Denmark)

    Rybtke, Morten; Hultqvist, Louise Dahl; Givskov, Michael

    2015-01-01

    Studies of biopsies from infectious sites, explanted tissue and medical devises have provided evidence that biofilms are the underlying cause of a variety of tissue-associated and implant-associated recalcitrant human infections. With a need for novel anti-biofilm treatment strategies, research...... in biofilm infection microbiology, biofilm formation mechanisms and biofilm-associated antimicrobial tolerance has become an important area in microbiology. Substantial knowledge about biofilm formation mechanisms, biofilm-associated antimicrobial tolerance and immune evasion mechanisms has been obtained...... through work with biofilms grown in in vitro experimental setups, and the relevance of this information in the context of chronic infections is being investigated by the use of animal models of infection. Because our current in vitro experimental setups and animal models have limitations, new advanced...

  10. Microevolution of Pseudomonas aeruginosa to a chronic pathogen of the cystic fibrosis lung.

    Science.gov (United States)

    Hogardt, Michael; Heesemann, Jürgen

    2013-01-01

    Pseudomonas aeruginosa is the leading pathogen of chronic cystic fibrosis (CF) lung infection. Life-long persistance of P. aeruginosa in the CF lung requires a sophisticated habitat-specific adaptation of this pathogen to the heterogeneous and fluctuating lung environment. Due to the high selective pressure of inflamed CF lungs, P. aeruginosa increasingly experiences complex physiological and morphological changes. Pulmonary adaptation of P. aeruginosa is mediated by genetic variations that are fixed by the repeating interplay of mutation and selection. In this context, the emergence of hypermutable phenotypes (mutator strains) obviously improves the microevolution of P. aeruginosa to the diverse microenvironments of the CF lung. Mutator phenotypes are amplified during CF lung disease and accelerate the intraclonal diversification of P. aeruginosa. The resulting generation of numerous subclonal variants is advantegous to prepare P. aeruginosa population for unpredictable stresses (insurance hypothesis) and thus supports long-term survival of this pathogen. Oxygen restriction within CF lung environment further promotes persistence of P. aeruginosa due to increased antibiotic tolerance, alginate production and biofilm formation. Finally, P. aeruginosa shifts from an acute virulent pathogen of early infection to a host-adapted chronic virulent pathogen of end-stage infection of the CF lung. Common changes that are observed among chronic P. aeruginosa CF isolates include alterations in surface antigens, loss of virulence-associated traits, increasing antibiotic resistances, the overproduction of the exopolysaccharide alginate and the modulation of intermediary and micro-aerobic metabolic pathways (Hogardt and Heesemann, Int J Med Microbiol 300(8):557-562, 2010). Loss-of-function mutations in mucA and lasR genes determine the transition to mucoidity and loss of quorum sensing, which are hallmarks of the chronic virulence potential of P. aeruginosa. Metabolic factors

  11. Relative contribution of Prevotella intermedia and Pseudomonas aeruginosa to lung pathology in airways of patients with cystic fibrosis

    DEFF Research Database (Denmark)

    Ulrich, Martina; Beer, Isabelle; Braitmaier, Peter;

    2010-01-01

    Patients with cystic fibrosis (CF) with Pseudomonas aeruginosa lung infections produce endobronchial mucus plugs allowing growth of obligate anaerobes including Prevotella spp. Whether obligate anaerobes contribute to the pathophysiology of CF lung disease is unknown.......Patients with cystic fibrosis (CF) with Pseudomonas aeruginosa lung infections produce endobronchial mucus plugs allowing growth of obligate anaerobes including Prevotella spp. Whether obligate anaerobes contribute to the pathophysiology of CF lung disease is unknown....

  12. Pseudomonas aeruginosa Quorum-Sensing Systems May Control Virulence Factor Expression in the Lungs of Patients with Cystic Fibrosis

    OpenAIRE

    Erickson, David L.; Endersby, Ryan; Kirkham, Amanda; Stuber, Kent; Vollman, Dolina D.; Rabin, Harvey R; Mitchell, Ian; Storey, Douglas G.

    2002-01-01

    Individuals with cystic fibrosis (CF) are commonly colonized with Pseudomonas aeruginosa. The chronic infections caused by P. aeruginosa are punctuated by acute exacerbations of the lung disease, which lead to significant morbidity and mortality. As regulators of virulence determinants, P. aeruginosa quorum-sensing systems may be active in the chronic lung infections associated with CF. We have examined the levels of autoinducer molecules and transcript accumulation from the bacterial populat...

  13. Pseudomonas aeruginosa alginate is refractory to Th1 immune response and impedes host immune clearance in a mouse model of acute lung infection

    DEFF Research Database (Denmark)

    Song, Zhijun; Wu, Hong; Ciofu, Oana;

    2003-01-01

    Pseudomonas aeruginosa is an opportunistic respiratory pathogen that accounts for most of the morbidity and mortality in cystic fibrosis (CF) patients. In CF-affected lungs, the bacteria undergo conversion from a non-mucoid to a non-tractable mucoid phenotype, due to overproduction of alginate...

  14. Vaccines for preventing infection with Pseudomonas aeruginosa in cystic fibrosis

    DEFF Research Database (Denmark)

    Johansen, Helle Krogh; Gøtzsche, Peter C

    2015-01-01

    BACKGROUND: Chronic pulmonary infection in cystic fibrosis results in progressive lung damage. Once colonisation of the lungs with Pseudomonas aeruginosa occurs, it is almost impossible to eradicate. Vaccines, aimed at reducing infection with Pseudomonas aeruginosa, have been developed...... in the vaccine group and 91 (1 severe) in the control group. In this large trial of a vaccine developed against flagella antigens, antibody titres against the epitopes contained in the vaccine were higher in the vaccine group compared to the placebo group (P Vaccines against....... This is an update of a previously published review. OBJECTIVES: To assess the effectiveness of vaccination against Pseudomonas aeruginosa in cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register using the terms vaccines AND pseudomonas (last search 30...

  15. Pseudomonas aeruginosa Diversification during Infection Development in Cystic Fibrosis Lungs—A Review

    Science.gov (United States)

    Sousa, Ana Margarida; Pereira, Maria Olívia

    2014-01-01

    Pseudomonas aeruginosa is the most prevalent pathogen of cystic fibrosis (CF) lung disease. Its long persistence in CF airways is associated with sophisticated mechanisms of adaptation, including biofilm formation, resistance to antibiotics, hypermutability and customized pathogenicity in which virulence factors are expressed according the infection stage. CF adaptation is triggered by high selective pressure of inflamed CF lungs and by antibiotic treatments. Bacteria undergo genetic, phenotypic, and physiological variations that are fastened by the repeating interplay of mutation and selection. During CF infection development, P. aeruginosa gradually shifts from an acute virulent pathogen of early infection to a host-adapted pathogen of chronic infection. This paper reviews the most common changes undergone by P. aeruginosa at each stage of infection development in CF lungs. The comprehensive understanding of the adaptation process of P. aeruginosa may help to design more effective antimicrobial treatments and to identify new targets for future drugs to prevent the progression of infection to chronic stages. PMID:25438018

  16. Cystic Fibrosis Transmembrane Conductance Regulator is an Epithelial Cell Receptor for Clearance of Pseudomonas aeruginosa from the Lung

    Science.gov (United States)

    Pier, Gerald B.; Grout, Martha; Zaidi, Tanweer S.

    1997-10-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride ion channel, but its relationship to the primary clinical manifestation of CF, chronic Pseudomonas aeruginosa pulmonary infection, is unclear. We report that CFTR is a cellular receptor for binding, endocytosing, and clearing P. aeruginosa from the normal lung. Murine cells expressing recombinant human wild-type CFTR ingested 30-100 times as many P. aeruginosa as cells lacking CFTR or expressing mutant Δ F508 CFTR protein. Purified CFTR inhibited ingestion of P. aeruginosa by human airway epithelial cells. The first extracellular domain of CFTR specifically bound to P. aeruginosa and a synthetic peptide of this region inhibited P. aeruginosa internalization in vivo, leading to increased bacterial lung burdens. CFTR clears P. aeruginosa from the lung, indicating a direct connection between mutations in CFTR and the clinical consequences of CF.

  17. Cytokine and surface receptor diversity of NK cells in resistant C3H/HeN and susceptible BALB/c mice with chronic Pseudomonas aeruginosa lung infection

    DEFF Research Database (Denmark)

    Calum, Henrik; Moser, Claus; Jensen, Peter Østrup;

    2003-01-01

    the infection in cystic fibrosis. Lung cell suspensions were depleted of lymphocytes by magnetic cell sorting. The concentrations of IFN-gamma, IL-1beta and GM-CSF were estimated by ELISA at day 1 and 2 after infection. Non-infected mice were used as controls. Flow cytometry was used to estimate the surface...

  18. 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...

  19. [Clinical features of Pseudomonas aeruginosa infections].

    Science.gov (United States)

    Sarlangue, J; Brissaud, O; Labrèze, C

    2006-10-01

    Pseudomonas aeruginosa is a ubiquitous environmental organism usually considered as opportunistic pathogen in immunocompromised subjects. However it can produce disease in healthy children, mainly on moist body sites. Familial, community and nosocomial outbreaks of cutaneous infections have been reported. Ecthyma gangrenosum is possible without bacteremia. P. aeruginosa is also the most common cause of otitis externa in swimmers and osteomyelitis after puncture wound of the foot.

  20. Lung infection

    Institute of Scientific and Technical Information of China (English)

    1995-01-01

    950304 The diagnosis and treatment of pulmonaryaspergilloma in the aged—a report of 17 cases.LI Di-anqin(李殿清),et al.Henan Provincial Pulmon DisHosp,Zhengzhou,450003.Chin J Geriatr 1994;13(6):338-339.Seventeen cases of pulmonary aspergilloma in theaged were reported.The primary diseases were pul-monary tuberculosis in 14 cases and pulmonary cyst,cancer of lung and pulmonary abscess in one each.In14 cases,the clinical manifestation was frequenthemoptysis;the occurrence rate was 82.4%.Among

  1. Pseudomonas aeruginosa vesicles associate with and are internalized by human lung epithelial cells

    Directory of Open Access Journals (Sweden)

    Kuehn Meta J

    2009-02-01

    Full Text Available Abstract Background Pseudomonas aeruginosa is the major pathogen associated with chronic and ultimately fatal lung infections in patients with cystic fibrosis (CF. To investigate how P. aeruginosa-derived vesicles may contribute to lung disease, we explored their ability to associate with human lung cells. Results Purified vesicles associated with lung cells and were internalized in a time- and dose-dependent manner. Vesicles from a CF isolate exhibited a 3- to 4-fold greater association with lung cells than vesicles from the lab strain PAO1. Vesicle internalization was temperature-dependent and was inhibited by hypertonic sucrose and cyclodextrins. Surface-bound vesicles rarely colocalized with clathrin. Internalized vesicles colocalized with the endoplasmic reticulum (ER marker, TRAPα, as well as with ER-localized pools of cholera toxin and transferrin. CF isolates of P. aeruginosa abundantly secrete PaAP (PA2939, an aminopeptidase that associates with the surface of vesicles. Vesicles from a PaAP knockout strain exhibited a 40% decrease in cell association. Likewise, vesicles from PAO1 overexpressing PaAP displayed a significant increase in cell association. Conclusion These data reveal that PaAP promotes the association of vesicles with lung cells. Taken together, these results suggest that P. aeruginosa vesicles can interact with and be internalized by lung epithelial cells and contribute to the inflammatory response during infection.

  2. Lung infection

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930120 A clinical study of 50 cases of legion-naires disease.WANG Baofa(王保法),et al.Dept Intern Med,2nd Affili Hosp,Hehei MedColl,Shijiazhuang,050000.Chin J Tuberc &Respir Dis 1992;15(5):266-268.The clinical features and X-ray manifesta-tions of 50 cases of legionnaires disease wereanalysed.8 cases might be due to nosocomial in-fection through breathing in flying particles ofthe saliva or phlegm.According to the mainclinical features,this disease could be dividedinto common pneumonia type,acute gastroen-teritis type,encephalopathy type,shock type,and acute renal insufficiency type.The differen-

  3. Expression of PPARγ and paraoxonase 2 correlated with Pseudomonas aeruginosa infection in cystic fibrosis.

    Directory of Open Access Journals (Sweden)

    Phoebe E Griffin

    Full Text Available The Pseudomonas aeruginosa quorum sensing signal molecule N-3-oxododecanoyl-l-homoserine lactone (3OC(12HSL can inhibit function of the mammalian anti-inflammatory transcription factor peroxisome proliferator activated receptor (PPARγ, and can be degraded by human paraoxonase (PON2. Because 3OC(12HSL is detected in lungs of cystic fibrosis (CF patients infected with P. aeruginosa, we investigated the relationship between P. aeruginosa infection and gene expression of PPARγ and PON2 in bronchoalveolar lavage fluid (BALF of children with CF. Total RNA was extracted from cell pellets of BALF from 43 children aged 6 months-5 years and analyzed by reverse transcription-quantitative real time PCR for gene expression of PPARγ, PON2, and P. aeruginosa lasI, the 3OC(12HSL synthase. Patients with culture-confirmed P. aeruginosa infection had significantly lower gene expression of PPARγ and PON2 than patients without P. aeruginosa infection. All samples that were culture-positive for P. aeruginosa were also positive for lasI expression. There was no significant difference in PPARγ or PON2 expression between patients without culture-detectable infection and those with non-Pseudomonal bacterial infection, so reduced expression was specifically associated with P. aeruginosa infection. Expression of both PPARγ and PON2 was inversely correlated with neutrophil counts in BALF, but showed no correlation with other variables evaluated. Thus, lower PPARγ and PON2 gene expression in the BALF of children with CF is associated specifically with P. aeruginosa infection and neutrophilia. We cannot differentiate whether this is a cause or the effect of P. aeruginosa infection, but propose that the level of expression of these genes may be a marker for susceptibility to early acquisition of P. aeruginosa in children with CF.

  4. Recent advances in the treatment of Pseudomonas aeruginosa infections in cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Høiby Niels

    2011-04-01

    Full Text Available Abstract Chronic Pseudomonas aeruginosa lung infection in cystic fibrosis (CF patients is caused by biofilm-growing mucoid strains. Biofilms can be prevented by early aggressive antibiotic prophylaxis or therapy, and they can be treated by chronic suppressive therapy. New results from one small trial suggest that addition of oral ciprofloxacin to inhaled tobramycin may reduce lung inflammation. Clinical trials with new formulations of old antibiotics for inhalation therapy (aztreonam lysine against chronic P. aeruginosa infection improved patient-reported outcome, lung function, time to acute exacerbations and sputum density of P. aeruginosa. Other drugs such as quinolones are currently under investigation for inhalation therapy. A trial of the use of anti-Pseudomonas antibiotics for long-term prophylaxis showed no effect in patients who were not already infected. Use of azithromycin to treat CF patients without P. aeruginosa infection did not improve lung function. Here I review the recent advances in the treatment of P. aeruginosa lung infections with a focus on inhalation treatments targeted at prophylaxis and chronic suppressive therapy.

  5. Impaired upregulation of keratinocyte growth factor in injured lungs induced by Pseudomonas aeruginosa in immunosuppressed rats

    Institute of Scientific and Technical Information of China (English)

    XU Jin-fu; QU Jie-ming; HE Li-xian; OU Zhou-luo

    2006-01-01

    Background The number of immunosupressed patients has increased in the past decades. Among them Pseudomonas aeruginosa (P. aeruginosa) is one of the leading bacteria for pneumonia that are associated with poor prognosis. However, the pathogenesis of P. aeruginosa pneumonia in immunosupressed patients is not understood completely. Previous reports showed keratinocyte growth factor (KGF) is associated with lung injury in immunocompetent hosts. In this study, we investigated the different reactions of lung injury, lung pathology and KGF expressions in P. aeruginosa pneumonia between immunosuppressed and immunocompetent rats.Methods Immunosuppression of male rats was induced by injecting immunosuppressive subcutaneously.Pneumonia was established by instilling P. aeruginous tracheally. The immunocompetent rats were the control group. Survival rate, lung histopathology, pulmonary permeability and oedema, KGF mRNA and protein expressions in lungs of both groups were investigated.Results The survival rate of immunosuppressed group was lower than that of immunocompetent group (33.3%vs 83.3%). After exposure to bacteria, pulmonary permeability and wet/dry ratio in immunosuppressed group were higher than those in immunocompetent group. Pulmonary congestion and haemorrhage were more intensive in immunosuppressed group compared to immunocompetent group. Apoptosis and necrosis were also observed in infected lungs of immunosuppressed rats. Although we detected KGF expressions in lungs of both groups after infection, the expressions of KGF protein and mRNA gene in immunosuppressed group were much lower than in immunocompetent group.Conclusions Compared with immunocompetent group, there was more intensive lung injury in immunosuppressed group. Severe lung injury may contribute to the poor prognosis of pneumonia. KGF expressions of pneumonia in immunosuppressed rats were less than those in immunocompetent ones.

  6. The implication of Pseudomonas aeruginosa biofilms in infections

    DEFF Research Database (Denmark)

    Rybtke, Morten T; Jensen, Peter Østrup; Høiby, Niels

    2011-01-01

    of infection in the lungs of cystic fibrosis patients and in chronic wounds. In this review we address the molecular basis of biofilm development by P. aeruginosa as well as the mechanisms employed by this bacterium in the increased tolerance displayed against antimicrobials. The complex build......-up of the extracellular matrix encasing the biofilm-associated bacteria as well as the elaborate signaling mechanisms employed by the bacterium enables it to withstand the continuous stresses imposed by the immune defense and administered antibiotics resulting in a state of chronic inflammation that damages the host....... The immune response leading to this chronic inflammation is described. Finally, novel treatment strategies against P. aeruginosa are described including, quorum-sensing inhibition and induced biofilm-dispersion. The tolerance towards currently available antimicrobials calls for development of alternative...

  7. Augmented effect of early antibiotic treatment in mice with experimental lung infections due to sequentially adapted mucoid strains of Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    van Gennip, M; Moser, Claus; Christensen, Louise D

    2009-01-01

    : A significant reduction in the number of bacteria was observed when initiating treatment 1 h post-infection compared with initiating treatment after 24 h, although the latest isolate avoided complete clearance. Early antibiotic treatment directed at the mucoid phenotype in mice also reduced the inflammation and...... cystic fibrosis (CF) patient at different time periods during chronic lung infection. Methods: BALB/c mice were challenged with alginate-embedded mucoid clinical isolates isolated in 1988, 1997 or 2003. Mice were euthanized on day 1, 2 or 3 post-infection for estimation of quantitative bacteriology......, histopathology, and measurement of granulocyte colony-stimulating factor (G-CSF) and macrophage inflammatory protein 2 (MIP-2). Results: There was a significant reduction of bacteria when comparing treatment initiated 1 h post-infection with treatment initiated after 24 h for isolates 1997 and 2003. Treatment...

  8. Pseudomonas aeruginosa airway infection recruits and modulates neutrophilic myeloid-derived suppressor cells

    Directory of Open Access Journals (Sweden)

    Hasan Halit Öz

    2016-11-01

    Full Text Available Pseudomonas aeruginosa is an opportunistic pathogen that causes infections mainly in patients with cystic fibrosis (CF lung disease. Despite innate and adaptive immune responses upon infection, P. aeruginosa is capable of efficiently escaping host defenses, but the underlying immune mechanisms remain poorly understood. Myeloid-derived suppressor cells (MDSCs are innate immune cells that are functionally characterized by their potential to suppress T- and natural killer (NK-cell responses. Here we demonstrate, using an airway in vivo infection model, that P. aeruginosa recruits and activates neutrophilic MDSCs, which functionally suppress T-cell responses. We further show that the CF gene defect (cystic fibrosis transmembrane conductance regulator, CFTR modulates the functionality, but not the recruitment or generation of neutrophilic MDSCs. Collectively, we define a mechanism by which P. aeruginosa airway infection undermines host immunity by modulating neutrophilic MDSCs in vivo.

  9. Pseudomonas aeruginosa adapts its iron uptake strategies in function of the type of infections

    Directory of Open Access Journals (Sweden)

    Pierre eCornelis

    2013-11-01

    Full Text Available Pseudomonas aeruginosa is a Gram-negative -Proteobacterium which is known for its capacity to colonize various niches, including some invertebrate and vertebrate hosts, making it one of the most frequent bacteria causing opportunistic infections. P. aeruginosa is able to cause acute as well as chronic infections and it uses different colonization and virulence factors to do so. Infections range from septicemia, urinary infections, burn wound colonization, and chronic colonization of the lungs of cystic fibrosis patients. Like the vast majority of organisms, P. aeruginosa needs iron to sustain growth. P. aeruginosa utilizes different strategies to take up iron, depending on the type of infection it causes. Two siderophores are produced by this bacterium, pyoverdine and pyochelin, characterized by high and low affinities for iron respectively. P. aeruginosa is also able to utilize different siderophores from other microorganisms (siderophore piracy. It can also take up heme from hemoproteins via two different systems. Under microaerobic or anaerobic conditions, P. aeruginosa is also able to take up ferrous iron via its Feo system using redox-cycling phenazines. Depending on the type of infection, P. aeruginosa can therefore adapt by switching from one iron uptake system to another as we will describe in this short review.

  10. Ginseng treatment reduces bacterial load and lung pathology in chronic Pseudomonas aeruginosa pneumonia in rats

    DEFF Research Database (Denmark)

    Song, Z; Johansen, H K; Faber, V

    1997-01-01

    the inflammation and antibody responses could be changed by treatment with the Chinese herbal medicine ginseng. An aqueous extract of ginseng was injected subcutaneously, and cortisone and saline were used as controls. Two weeks after challenge with P. aeruginosa, the ginseng-treated group showed a significantly...... resembling a TH1-like response. On the basis of these results it is suggested that ginseng may have the potential to be a promising natural medicine, in conjunction with other forms of treatment, for CF patients with chronic P. aeruginosa lung infection....

  11. Transcriptional Activation of Mucin by Pseudomonas aeruginosa Lipopolysaccharide in the Pathogenesis of Cystic Fibrosis Lung Disease

    Science.gov (United States)

    Li, Jian-Dong; Dohrman, Austin F.; Gallup, Marianne; Miyata, Susumu; Gum, James R.; Kim, Young S.; Nadel, Jay A.; Prince, Alice; Basbaum, Carol B.

    1997-02-01

    An unresolved question in cystic fibrosis (CF) research is how mutations of the CF transmembrane conductance regulator, a CI ion channel, cause airway mucus obstruction leading to fatal lung disease. Recent evidence has linked the CF transmembrane conductance regulator mutation to the onset and persistence of Pseudomonas aeruginosa infection in the airways, and here we provide evidence directly linking P. aeruginosa infection to mucus overproduction. We show that P. aeruginosa lipopolysaccharide profoundly upregulates transcription of the mucin gene MUC 2 in epithelial cells via inducible enhancer elements and that this effect is blocked by the tyrosine kinase inhibitors genistein and tyrphostin AG 126. These findings improve our understanding of CF pathogenesis and suggest that the attenuation of mucin production by lipopolysaccharide antagonists and tyrosine kinase inhibitors could reduce morbidity and mortality in this disease.

  12. Nosocomial infections due to Pseudomonas aeruginosa: review of recent trends.

    Science.gov (United States)

    Cross, A; Allen, J R; Burke, J; Ducel, G; Harris, A; John, J; Johnson, D; Lew, M; MacMillan, B; Meers, P

    1983-01-01

    The role of Pseudomonas aeruginosa in nosocomial infections occurring since 1975 is reviewed. Data from the National Nosocomial Infections Study conducted by the Centers for Disease Control, from individual medical centers, and from the literature were used to compare the relative frequency of occurrence of nosocomial infection caused by P. aeruginosa with that of infection caused by other gram-negative bacilli. The relative frequency of P. aeruginosa as a nosocomial pathogen has increased, although wide variations are seen among individual medical centers. P. aeruginosa continues to be a major pathogen among patients with immunosuppression, cystic fibrosis, malignancy, and trauma. While Staphylococcus aureus has become the predominant pathogen in some large burn centers, P. aeruginosa is the most important gram-negative pathogen. Periodic review of the epidemiology of P. aeruginosa infection is warranted in view of the changing incidence of infection caused by this organism.

  13. Characterization of JG024, a pseudomonas aeruginosa PB1-like broad host range phage under simulated infection conditions

    Directory of Open Access Journals (Sweden)

    Rohde Manfred

    2010-11-01

    Full Text Available Abstract Background Pseudomonas aeruginosa causes lung infections in patients suffering from the genetic disorder Cystic Fibrosis (CF. Once a chronic lung infection is established, P. aeruginosa cannot be eradicated by antibiotic treatment. Phage therapy is an alternative to treat these chronic P. aeruginosa infections. However, little is known about the factors which influence phage infection of P. aeruginosa under infection conditions and suitable broad host range phages. Results We isolated and characterized a phage, named JG024, which infects a broad range of clinical and environmental P. aeruginosa strains. Sequencing of the phage genome revealed that the phage JG024 is highly related to the ubiquitous and conserved PB1-like phages. The receptor of phage JG024 was determined as lipopolysaccharide. We used an artificial sputum medium to study phage infection under conditions similar to a chronic lung infection. Alginate production was identified as a factor reducing phage infectivity. Conclusions Phage JG024 is a suitable broad host range phage which could be used in phage therapy. Phage infection experiments under simulated chronic lung infection conditions showed that alginate production reduces phage infection efficiency.

  14. Interference of Pseudomonas aeruginosa signalling and biofilm formation for infection control

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas; Tolker-Nielsen, Tim; Høiby, Niels;

    2010-01-01

    Pseudomonas aeruginosa is the best described bacterium with regards to quorum sensing (QS), in vitro biofilm formation and the development of antibiotic tolerance. Biofilms composed of P. aeruginosa are thought to be the underlying cause of many chronic infections, including those in wounds...... and in the lungs of patients with cystic fibrosis. In this review, we provide an overview of the molecular mechanisms involved in QS, QS-enabled virulence, biofilm formation and biofilm-enabled antibiotic tolerance. We now have substantial knowledge of the multicellular behaviour of P. aeruginosa in vitro. A major...

  15. Effects of quorum sensing system lasR/rhlR gene on the expression of Foxp3, TGF-β1 and IL-10 of lung tissue in tracheal intubation model rat with Pseudomonas aeruginosa biofilm infection

    Directory of Open Access Journals (Sweden)

    Qing-qing XIANG

    2016-03-01

    Full Text Available Objective  To investigate the effects of lasR/rhlR gene on Foxp3, TGF-β1 and IL-10 of lung tissue in rat tracheal intubation model with biofilm infection of Pseudomonas aeruginosa (Ps. aer wild strain (PAO1 and quorum sensing (QS deficient strain (ΔlasRΔrhlR. Methods  Twenty-one SD rats were randomly assigned into 3 groups (7 each: ΔlasRΔrhlR-treated group, PAO1-treated group and sterile control group. Biofilms (BF were cultured in vitro, and the BF coated tube (infected respectively with Ps. aer PAO1 strain, ΔlasRΔrhlR strain, or with asepsis was inserted into the trachea to establish the rat model. The rats were sacrificed on the 7th day after intubation. Colony count of lung tissue homogenate (cfu and lung HE staining were performed, and IL-10 content in bronchoalveolar lavage fluid (BALF, TGF-β1 in lung tissue, and the expression of Foxp3 mRNA in lung cells were determined. Results  The bacterial counts were significantly higher in PAO1 and ΔlasRΔrhlR groups than that in sterile control group, and the counts were obviously higher in PAO1 group (10 400.00±6313.70/g lung tissue than that in ΔlasRΔrhlR group (975.00±559.97/g lung tissue, P<0.05. There was no significant pathological changes in lung tissue in sterile control group, while the bronchi and blood vessels in PAO1 group were infiltrated by a large number of inflammatory cells and complicated with alveolar septum thickening and local abscess and necrosis. The pathological changes were milder in ΔlasRΔrhlR group than in PAO1 group; the expression of Foxp3 mRNA was higher in the two Ps. aer infected groups than that in sterile control group (0.65±0.32, and it was significantly higher in PAO1 group (4.62±1.07 than in ΔlasRΔrhlR group (2.15±1.43, P<0.05. The accumulated optical density value of TGF-β1 was significantly higher in the two Ps. aer infected groups than in sterile control group (3721.66±1412.95, and significantly higher in PAO1 group (65 090.56±33

  16. Controlled trial of inhaled budesonide in patients with cystic fibrosis and chronic bronchopulmonary Psuedomonas aeruginosa infection

    DEFF Research Database (Denmark)

    Bisgaard, H; Pedersen, S S; Nielsen, K G;

    1997-01-01

    The efficacy and safety of anti-inflammatory treatment with inhaled glucocorticosteroids in patients with cystic fibrosis (CF) and complicating chronic Pseudomonas aeruginosa (P.a.) lung infection was studied in a placebo-controlled, parallel, double-blind single center trial. Active treatment...

  17. Physiological levels of nitrate support anoxic growth by denitrification of Pseudomonas aeruginosa at growth rates reported in cystic fibrosis lungs and sputum

    DEFF Research Database (Denmark)

    Klitten, Laura Line; Alhede, Morten; Kolpen, Mette;

    2014-01-01

    Chronic Pseudomonas aeruginosa lung infection is the most severe complication in patients with cystic fibrosis (CF). The infection is characterized by the formation of biofilm surrounded by numerous polymorphonuclear leukocytes (PMNs) and strong O2 depletion in the endobronchial mucus. We have...... reported that O2 is mainly consumed by the activated PMNs, while O2 consumption by aerobic respiration is diminutive and nitrous oxide (N2O) is produced in infected CF sputum. This suggests that the reported growth rates of P. aeruginosa in lungs and sputum may result from anaerobic respiration using...... comparable to our reported growth rates in the majority of P. aeruginosa cells in CF lungs and sputum. Thus, we have demonstrated that denitrification is required for P. aeruginosa growth in infected endobronchial CF mucus....

  18. Experimental chronic Pseudomonas aeruginosa lung infection in rats. Non-specific stimulation with LPS reduces lethality as efficiently as specific immunization

    DEFF Research Database (Denmark)

    Lange, K H; Hougen, H P; Høiby, N

    1995-01-01

    stimulation of the non-specific defence mechanisms by Escherichia coli lipopolysaccharide (LPS) or P. aeruginosa sonicate, or the acquired specific immune response by vaccination with the same bacterial antigens. One day prior to challenge with P. aeruginosa embedded in alginate beads, rats were stimulated...... to earlier recruitment of PMNs most likely mediated by either cytokines and other chemotactic factors (stimulated group) or the immune response in concert with the complement cascade (vaccinated group). The results of the present and previous vaccination studies show that it is possible to improve survival...

  19. The implication of Pseudomonas aeruginosa biofilms in infections

    DEFF Research Database (Denmark)

    Rybtke, Morten Theil; Jensen, Peter Ø; Høiby, Niels

    2011-01-01

    of infection in the lungs of cystic fibrosis patients and in chronic wounds. In this review we address the molecular basis of biofilm development by P. aeruginosa as well as the mechanisms employed by this bacterium in the increased tolerance displayed against antimicrobials. The complex build......-up of the extracellular matrix encasing the biofilm-associated bacteria as well as the elaborate signaling mechanisms employed by the bacterium enables it to withstand the continuous stresses imposed by the immune defense and administered antibiotics resulting in a state of chronic inflammation that damages the host...... treatment strategies where the underlying targets are less prone for resistance development as bacteria, in retrospect, have a unique ability to evade the actions of classic antibiotics....

  20. Molecular epidemiology and dynamics of Pseudomonas aeruginosa populations in lungs of cystic fibrosis patients

    DEFF Research Database (Denmark)

    Jelsbak, Lars; Johansen, Helle Krogh; Frost, Anne Louise Viborg;

    2007-01-01

    The ability to establish lifelong persistent infections is a fundamental aspect of the interactions between many pathogenic microorganisms and their mammalian hosts. One example is chronic lung infections by the opportunistic pathogen Pseudomonas aeruginosa in cystic fibrosis (CF) patients...... clones that have evolved into highly successful colonizers of CF patient airways. A significant component of the evolutionary success of these two clones has been their efficient transmissibility among the CF patients. The two clones have been present and transmitted among different CF patients for more...

  1. Sinus surgery can improve quality of life, lung infections, and lung function in patients with primary ciliary dyskinesia

    DEFF Research Database (Denmark)

    Alanin, Mikkel Christian; Aanaes, Kasper; Høiby, Niels;

    2016-01-01

    BACKGROUND: Chronic rhinosinusitis (CRS) and bacterial sinusitis are ubiquitous in patients with primary ciliary dyskinesia (PCD). From the sinuses, Pseudomonas aeruginosa can infect the lungs. METHODS: We studied the effect of endoscopic sinus surgery (ESS) on symptoms of CRS and lower airway...... patients (62%). Four patients with preoperative P. aeruginosa lung colonization (25%) had no regrowth during follow-up; 2 of these had P. aeruginosa sinusitis. Sinonasal symptoms were improved 12 months after ESS and we observed a trend toward better lung function after ESS. CONCLUSION: We demonstrated...

  2. Pseudomonas aeruginosa quorum-sensing systems may control virulence factor expression in the lungs of patients with cystic fibrosis.

    Science.gov (United States)

    Erickson, David L; Endersby, Ryan; Kirkham, Amanda; Stuber, Kent; Vollman, Dolina D; Rabin, Harvey R; Mitchell, Ian; Storey, Douglas G

    2002-04-01

    Individuals with cystic fibrosis (CF) are commonly colonized with Pseudomonas aeruginosa. The chronic infections caused by P. aeruginosa are punctuated by acute exacerbations of the lung disease, which lead to significant morbidity and mortality. As regulators of virulence determinants, P. aeruginosa quorum-sensing systems may be active in the chronic lung infections associated with CF. We have examined the levels of autoinducer molecules and transcript accumulation from the bacterial populations found in the lungs of patients with CF. We detected biologically active levels of N-(3-oxododecanoyl)-L-homoserine (3-oxo-C12-HSL) and N-butyryl-L-homoserine lactone (C4-HSL) in sputum from CF patients. Interestingly, it appears that C4-HSL is less frequently detected than 3-oxo-C12-HSL in the lungs of patients with CF. We also examined the transcription of the autoinducer synthase gene lasI and showed that it is frequently expressed in the lungs of patients with CF. We observed a significant correlation between the expression of lasI and four target genes of the Las quorum-sensing system. Taken together, our results indicate that quorum-sensing systems are active and may control virulence factor expression in the lungs of patients with CF.

  3. Modulation of Pseudomonas aeruginosa lipopolysaccharide-induced lung inflammation by chronic iron overload in rat.

    Science.gov (United States)

    Lê, Bá Vuong; Khorsi-Cauet, Hafida; Bach, Véronique; Gay-Quéheillard, Jérôme

    2012-03-01

    Iron constitutes a critical nutrient source for bacterial growth, so iron overload is a risk factor for bacterial infections. This study aimed at investigating the role of iron overload in modulating bacterial endotoxin-induced lung inflammation. Weaning male Wistar rats were intraperitoneally injected with saline or iron sucrose [15 mg kg(-1) body weight (bw), 3 times per week, 4 weeks]. They were then intratracheally injected with Pseudomonas aeruginosa lipopolysaccharide (LPS) (5 μg kg(-1) bw) or saline. Inflammatory indices were evaluated 4 or 18 h post-LPS/saline injection. At 4 h, LPS-treated groups revealed significant increases in the majority of inflammatory parameters (LPS-binding protein (LBP), immune cell recruitment, inflammatory cytokine synthesis, myeloperoxidase activity, and alteration of alveolar-capillary permeability), as compared with control groups. At 18 h, these parameters reduced strongly with the exception for LBP content and interleukin (IL)-10. In parallel, iron acted as a modulator of immune cell recruitment; LBP, tumor necrosis factor-α, cytokine-induced neutrophil chemoattractant 3, and IL-10 synthesis; and alveolar-capillary permeability. Therefore, P. aeruginosa LPS may only act as an acute lung inflammatory molecule, and iron overload may modulate lung inflammation by enhancing different inflammatory parameters. Thus, therapy for iron overload may be a novel and efficacious approach for the prevention and treatment of bacterial lung inflammations.

  4. Antimicrobial resistance, respiratory tract infections and role of biofilms in lung infections in cystic fibrosis patients

    DEFF Research Database (Denmark)

    Ciofu, Oana; Tolker-Nielsen, Tim; Jensen, Peter Østrup

    2015-01-01

    Lung infection is the main cause of morbidity and mortality in patients with cystic fibrosis and is mainly dominated by Pseudomonas aeruginosa. The biofilm mode of growth makes eradication of the infection impossible, and it causes a chronic inflammation in the airways. The general mechanisms of ...... of adaptive evolution of the persisting bacteria imposes important therapeutic challenges and requires development of new drug delivery systems able to reach the different niches occupied by the bacteria in the lung of cystic fibrosis patients....

  5. Initial Pseudomonas aeruginosa infection in patients with cystic fibrosis: characteristics of eradicated and persistent isolates

    DEFF Research Database (Denmark)

    Tramper-Stranders, G. A.; van der Ent, C. K.; Molin, Søren;

    2012-01-01

    Clin Microbiol Infect 2012; 18: 567574 Abstract Despite intensive eradication therapy, some CF patients with early Pseudomonas aeruginosa infection rapidly develop a chronic infection. To elucidate factors associated with this persistence, bacterial characteristics of early P. aeruginosa isolates...

  6. Challenges with current inhaled treatments for chronic Pseudomonas aeruginosa infection in patients with cystic fibrosis.

    LENUS (Irish Health Repository)

    Greally, Peter

    2012-06-01

    Pseudomonas aeruginosa (Pa) is the predominant pathogen infecting the airways of patients with cystic fibrosis (CF). Initial colonization is usually transient and associated with non-mucoid strains, which can be eradicated if identified early. This strategy can prevent, or at least delay, chronic Pa infection, which eventually develops in the majority of patients by their late teens or early adulthood. This article discusses the management and latest treatment developments of Pa lung infection in patients with CF, with a focus on nebulized antibiotic therapy.

  7. SIV Infection of Lung Macrophages.

    Directory of Open Access Journals (Sweden)

    Yue Li

    Full Text Available HIV-1 depletes CD4+ T cells in the blood, lymphatic tissues, gut and lungs. Here we investigated the relationship between depletion and infection of CD4+ T cells in the lung parenchyma. The lungs of 38 Indian rhesus macaques in early to later stages of SIVmac251 infection were examined, and the numbers of CD4+ T cells and macrophages plus the frequency of SIV RNA+ cells were quantified. We showed that SIV infected macrophages in the lung parenchyma, but only in small numbers except in the setting of interstitial inflammation where large numbers of SIV RNA+ macrophages were detected. However, even in this setting, the number of macrophages was not decreased. By contrast, there were few infected CD4+ T cells in lung parenchyma, but CD4+ T cells were nonetheless depleted by unknown mechanisms. The CD4+ T cells in lung parenchyma were depleted even though they were not productively infected, whereas SIV can infect large numbers of macrophages in the setting of interstitial inflammation without depleting them. These observations point to the need for future investigations into mechanisms of CD4+ T cell depletion at this mucosal site, and into mechanisms by which macrophage populations are maintained despite high levels of infection. The large numbers of SIV RNA+ macrophages in lungs in the setting of interstitial inflammation indicates that lung macrophages can be an important source for SIV persistent infection.

  8. Mucoid Pseudomonas aeruginosa isolates maintain the biofilm formation capacity and the gene expression profiles during the chronic lung infection of CF patients

    DEFF Research Database (Denmark)

    Lee, Bao le ri; Schjerling, Charlotte K.; Kirkby, Nikolai;

    2011-01-01

    Danish CF patients were investigated. The in vitro biofilm formation capacity was studied under static and flow through conditions and the global gene expression profiles were investigated by Affymetrix GeneChip. Regulatory genes of alginate production and quorum sensing (QS) system were sequenced...... and measurements of the alginate production and the detection of the QS signal molecules were performed. Comparisons of mucoid and non-mucoid isolates from early and late stages of the infection showed that the mucoid phenotype maintained over a decade the capacity to form in vitro biofilm and showed an unaltered...

  9. Comparison of culture and qPCR for the detection of Pseudomonas aeruginosa in not chronically infected cystic fibrosis patients

    Directory of Open Access Journals (Sweden)

    Boboli Hedwige

    2010-09-01

    Full Text Available Abstract Background Pseudomonas aeruginosa is the major respiratory pathogen causing severe lung infections among CF patients, leading to high morbidity and mortality. Once infection is established, early antibiotic treatment is able to postpone the transition to chronic lung infection. In order to optimize the early detection, we compared the sensitivity of microbiological culture and quantitative PCR (qPCR for the detection of P. aeruginosa in respiratory samples of not chronically infected CF patients. Results In this national study, we followed CF patients during periods between 1 to 15 months. For a total of 852 samples, 729 (86% remained P. aeruginosa negative by both culture and qPCR, whereas 89 samples (10% were positive by both culture and qPCR. Twenty-six samples were negative by culture but positive by qPCR, and 10 samples were positive by culture but remained negative by qPCR. Five of the 26 patients with a culture negative, qPCR positive sample became later P. aeruginosa positive both by culture and qPCR. Conclusion Based on the results of this study, it can be concluded that qPCR may have a predictive value for impending P. aeruginosa infection for only a limited number of patients.

  10. Host genetic background influences the response to the opportunistic Pseudomonas aeruginosa infection altering cell-mediated immunity and bacterial replication.

    Directory of Open Access Journals (Sweden)

    Maura De Simone

    Full Text Available Pseudomonas aeruginosa is a common cause of healthcare-associated infections including pneumonia, bloodstream, urinary tract, and surgical site infections. The clinical outcome of P. aeruginosa infections may be extremely variable among individuals at risk and patients affected by cystic fibrosis. However, risk factors for P. aeruginosa infection remain largely unknown. To identify and track the host factors influencing P. aeruginosa lung infections, inbred immunocompetent mouse strains were screened in a pneumonia model system. A/J, BALB/cJ, BALB/cAnNCrl, BALB/cByJ, C3H/HeOuJ, C57BL/6J, C57BL/6NCrl, DBA/2J, and 129S2/SvPasCRL mice were infected with P. aeruginosa clinical strain and monitored for body weight and mortality up to seven days. The most deviant survival phenotypes were observed for A/J, 129S2/SvPasCRL and DBA/2J showing high susceptibility while BALB/cAnNCrl and C3H/HeOuJ showing more resistance to P. aeruginosa infection. Next, one of the most susceptible and resistant mouse strains were characterized for their deviant clinical and immunological phenotype by scoring bacterial count, cell-mediated immunity, cytokines and chemokines profile and lung pathology in an early time course. Susceptible A/J mice showed significantly higher bacterial burden, higher cytokines and chemokines levels but lower leukocyte recruitment, particularly neutrophils, when compared to C3H/HeOuJ resistant mice. Pathologic scores showed lower inflammatory severity, reduced intraluminal and interstitial inflammation extent, bronchial and parenchymal involvement and diminished alveolar damage in the lungs of A/J when compared to C3H/HeOuJ. Our findings indicate that during an early phase of infection a prompt inflammatory response in the airways set the conditions for a non-permissive environment to P. aeruginosa replication and lock the spread to other organs. Host gene(s may have a role in the reduction of cell-mediated immunity playing a critical role in

  11. Host genetic background influences the response to the opportunistic Pseudomonas aeruginosa infection altering cell-mediated immunity and bacterial replication.

    Science.gov (United States)

    De Simone, Maura; Spagnuolo, Lorenza; Lorè, Nicola Ivan; Rossi, Giacomo; Cigana, Cristina; De Fino, Ida; Iraqi, Fuad A; Bragonzi, Alessandra

    2014-01-01

    Pseudomonas aeruginosa is a common cause of healthcare-associated infections including pneumonia, bloodstream, urinary tract, and surgical site infections. The clinical outcome of P. aeruginosa infections may be extremely variable among individuals at risk and patients affected by cystic fibrosis. However, risk factors for P. aeruginosa infection remain largely unknown. To identify and track the host factors influencing P. aeruginosa lung infections, inbred immunocompetent mouse strains were screened in a pneumonia model system. A/J, BALB/cJ, BALB/cAnNCrl, BALB/cByJ, C3H/HeOuJ, C57BL/6J, C57BL/6NCrl, DBA/2J, and 129S2/SvPasCRL mice were infected with P. aeruginosa clinical strain and monitored for body weight and mortality up to seven days. The most deviant survival phenotypes were observed for A/J, 129S2/SvPasCRL and DBA/2J showing high susceptibility while BALB/cAnNCrl and C3H/HeOuJ showing more resistance to P. aeruginosa infection. Next, one of the most susceptible and resistant mouse strains were characterized for their deviant clinical and immunological phenotype by scoring bacterial count, cell-mediated immunity, cytokines and chemokines profile and lung pathology in an early time course. Susceptible A/J mice showed significantly higher bacterial burden, higher cytokines and chemokines levels but lower leukocyte recruitment, particularly neutrophils, when compared to C3H/HeOuJ resistant mice. Pathologic scores showed lower inflammatory severity, reduced intraluminal and interstitial inflammation extent, bronchial and parenchymal involvement and diminished alveolar damage in the lungs of A/J when compared to C3H/HeOuJ. Our findings indicate that during an early phase of infection a prompt inflammatory response in the airways set the conditions for a non-permissive environment to P. aeruginosa replication and lock the spread to other organs. Host gene(s) may have a role in the reduction of cell-mediated immunity playing a critical role in the control of P

  12. Phenotypic shift in Pseudomonas aeruginosa populations from cystic fibrosis lungs after 2-week antipseudomonal treatment

    DEFF Research Database (Denmark)

    Fernández-Barat, Laia; Ciofu, Oana; Kragh, Kasper N

    2017-01-01

    BACKGROUND: The influence of suppressive therapy on the different P. aeruginosa phenotypes harbored in the lungs of cystic fibrosis (CF) patients remains unclear. Our aim was to investigate the phenotypic changes (mucoidy, hypermutability, antibiotic resistance, transcriptomic profiles and biofil...

  13. Pseudomonas aeruginosa dose response and bathing water infection.

    Science.gov (United States)

    Roser, D J; van den Akker, B; Boase, S; Haas, C N; Ashbolt, N J; Rice, S A

    2014-03-01

    Pseudomonas aeruginosa is the opportunistic pathogen mostly implicated in folliculitis and acute otitis externa in pools and hot tubs. Nevertheless, infection risks remain poorly quantified. This paper reviews disease aetiologies and bacterial skin colonization science to advance dose-response theory development. Three model forms are identified for predicting disease likelihood from pathogen density. Two are based on Furumoto & Mickey's exponential 'single-hit' model and predict infection likelihood and severity (lesions/m2), respectively. 'Third-generation', mechanistic, dose-response algorithm development is additionally scoped. The proposed formulation integrates dispersion, epidermal interaction, and follicle invasion. The review also details uncertainties needing consideration which pertain to water quality, outbreaks, exposure time, infection sites, biofilms, cerumen, environmental factors (e.g. skin saturation, hydrodynamics), and whether P. aeruginosa is endogenous or exogenous. The review's findings are used to propose a conceptual infection model and identify research priorities including pool dose-response modelling, epidermis ecology and infection likelihood-based hygiene management.

  14. Acute intratracheal Pseudomonas aeruginosa infection in cystic fibrosis mice is age-independent

    Directory of Open Access Journals (Sweden)

    Munder Antje

    2011-11-01

    Full Text Available Abstract Background Since the discovery of the human CFTR gene in 1989 various mouse models for cystic fibrosis (CF have been generated and used as a very suitable and popular tool to approach research on this life-threatening disease. Age related changes regarding the course of disease and susceptibility towards pulmonary infections have been discussed in numerous studies. Methods Here, we investigated CftrTgH(neoimHgu and Cftrtm1Unc-Tg(FABPCFTR1Jaw/J CF mice and their non-CF littermates during an acute lung infection with Pseudomonas aeruginosa for age dependent effects of their lung function and immune response. Mice younger than three or older than six months were intratracheally infected with P. aeruginosa TBCF10839. The infection was monitored by lung function of the animals using non-invasive head-out spirometry and the time course of physiological parameters over 192 hours. Quantitative bacteriology and lung histopathology of a subgroup of animals were used as endpoint parameters. Results Age-dependent changes in lung function and characteristic features for CF like a shallower, faster breathing pattern were observed in both CF mouse models in uninfected state. In contrast infected CF mice did not significantly differ from their non-CF littermates in susceptibility and severity of lung infection in both mouse models and age groups. The transgenic Cftrtm1Unc-Tg(FABPCFTR1Jaw/J and their non-CF littermates showed a milder course of infection than the CftrTgH(neoimHgu CF and their congenic C57Bl/6J non-CF mice suggesting that the genetic background was more important for outcome than Cftr dysfunction. Conclusions Previous investigations of the same mouse lines have shown a higher airway susceptibility of older CF mice to intranasally applied P. aeruginosa. The different outcome of intranasal and intratracheal instillation of bacteria implies that infected CF epithelium is impaired during the initial colonization of upper airways, but not in

  15. Impaired Pulmonary Defense Against Pseudomonas aeruginosa in VEGF Gene Inactivated Mouse Lung

    Science.gov (United States)

    Breen, Ellen C.; Malloy, Jaret L.; Tang, Kechun; Xia, Feng; Fu, Zhenxing; Hancock, Robert E. W.; Overhage, Joerg; Wagner, Peter D.; Spragg, Roger G.

    2012-01-01

    Repeated bacterial and viral infections are known to contribute to worsening lung function in several respiratory diseases, including asthma, cystic fibrosis and chronic obstructive pulmonary disease (COPD). Previous studies have reported alveolar wall cell apoptosis and parenchymal damage in adult pulmonary VEGF gene ablated mice. We hypothesized that VEGF expressed by type II cells is also necessary to provide an effective host defense against bacteria in part by maintaining surfactant homeostasis. Therefore, Pseudomonas aeruginosa (PAO1) levels were evaluated in mice following lung-targeted VEGF gene inactivation, and alterations in VEGF-dependent type II cell function were evaluated by measuring surfactant homeostasis in mouse lungs and isolated type II cells. In VEGF-deficient lungs increased PAO1 levels and pro-inflammatory cytokines, TNFα and IL-6, were detected 24 hours after bacterial instillation compared to control lungs. In vivo lung-targeted VEGF gene deletion (57% decrease in total pulmonary VEGF) did not alter alveolar surfactant or tissue disaturated phosphatidylcholine (DSPC) levels. However, sphingomyelin content, choline phosphate cytidylyltransferase (CCT) mRNA and SP-D expression were decreased. In isolated type II cells an 80% reduction of VEGF protein resulted in decreases in total phospholipids (PL), DSPC, DSPC synthesis, surfactant associated proteins (SP)-B and -D, and the lipid transporters, ABCA1 and Rab3D. TPA-induced DSPC secretion and apoptosis were elevated in VEGF-deficient type II cells. These results suggest a potential protective role for type II cell-expressed VEGF against bacterial initiated infection. PMID:22718316

  16. Imipenem-resistant Pseudomonas aeruginosa: risk factors for nosocomial infections.

    Science.gov (United States)

    Onguru, Pinar; Erbay, Ayse; Bodur, Hurrem; Baran, Gulseren; Akinci, Esragul; Balaban, Neriman; Cevik, Mustafa Aydin

    2008-12-01

    The aim of this study was to determine the risk factors for nosocomial infections of imipenem-resistant Pseudomonas aeruginosa (IRPA). A prospective case-control study was performed at a tertiary care hospital in Ankara from January to December 2004. The patients with nosocomial P. aeruginosa infection were included in the study. The features of the patients with IRPA infections were compared to those with imipenem-sensitive P. aeruginosa (ISPA) infections. Only the first isolation of P. aeruginosa was considered. Nosocomial infections were defined according to Center for Disease Control (CDC) criteria. IRPA was isolated from 75 (44.1%) patients, and ISPA was isolated from 95 (55.9%) patients during the study period. IRPA were most frequently isolated from endotracheal aspirate (19%) cultures (p=0.048), whereas ISPA were most frequently isolated from urine (28%) cultures (p=0.023). In multivariate analysis, a longer duration of hospital stay until P. aeruginosa isolation (odds ratio [OR], 1.027; 95% confidence interval [CI], 1.002-1.054, p=0.034), arterial catheter administration (OR, 2.508; 95% CI, 1.062-5.920, p=0.036), vancomycin (OR, 2.882; 95% CI, 1.130-7.349, p=0.027), piperacillin-tazobactam (OR, 6.425; 95% CI, 2.187-18.875, p=0.001), and imipenem (OR, 3.580; 95% CI, 1.252-10.245, p=0.017) treatment within the 14 days before isolation of IRPA were independently associated with imipenem resistance. It was concluded that treatment with imipenem, vancomycin and piperacillin-tazobactam were major risk factors for IRPA infections in hospitalized patients. The nosocomial occurrence of IRPA was also strongly related to the duration of hospital stay, arterial catheter administration.

  17. Role of IL-1β in experimental cystic fibrosis upon P. aeruginosa infection.

    Directory of Open Access Journals (Sweden)

    Jennifer Palomo

    Full Text Available Cystic fibrosis is associated with increased inflammatory responses to pathogen challenge. Here we revisited the role of IL-1β in lung pathology using the experimental F508del-CFTR murine model on C57BL/6 genetic background (Cftr(tm1eur or d/d, on double deficient for d/d and type 1 interleukin-1 receptor (d/d X IL-1R1-/-, and antibody neutralization. At steady state, young adult d/d mice did not show any signs of spontaneous lung inflammation. However, IL-1R1 deficiency conferred partial protection to repeated P. aeruginosa endotoxins/LPS lung instillation in d/d mice, as 50% of d/d mice succumbed to inflammation, whereas all d/d x IL-1R1-/- double mutants survived with lower initial weight loss and less pulmonary collagen and mucus production, suggesting that the absence of IL-1R1 signaling is protective in d/d mice in LPS-induced lung damage. Using P. aeruginosa acute lung infection we found heightened neutrophil recruitment in d/d mice with higher epithelial damage, increased bacterial load in BALF, and augmented IL-1β and TNF-α in parenchyma as compared to WT mice. Thus, F508del-CFTR mice show enhanced IL-1β signaling in response to P. aeruginosa. IL-1β antibody neutralization had no effect on lung homeostasis in either d/d or WT mice, however P. aeruginosa induced lung inflammation and bacterial load were diminished by IL-1β antibody neutralization. In conclusion, enhanced susceptibility to P. aeruginosa in d/d mice correlates with an excessive inflammation and with increased IL-1β production and reduced bacterial clearance. Further, we show that neutralization of IL-1β in d/d mice through the double mutation d/d x IL-1R1-/- and in WT via antibody neutralization attenuates inflammation. This supports the notion that intervention in the IL-1R1/IL-1β pathway may be detrimental in CF patients.

  18. Pseudomonas aeruginosa adaptation to lungs of cystic fibrosis patients leads to lowered resistance to phage and protist enemies.

    Directory of Open Access Journals (Sweden)

    Ville-Petri Friman

    Full Text Available Pathogenic life styles can lead to highly specialized interactions with host species, potentially resulting in fitness trade-offs in other ecological contexts. Here we studied how adaptation of the environmentally transmitted bacterial pathogen, Pseudomonas aeruginosa, to cystic fibrosis (CF patients affects its survival in the presence of natural phage (14/1, ΦKZ, PNM and PT7 and protist (Tetrahymena thermophila and Acanthamoebae polyphaga enemies. We found that most of the bacteria isolated from relatively recently intermittently colonised patients (1-25 months, were innately phage-resistant and highly toxic for protists. In contrast, bacteria isolated from long time chronically infected patients (2-23 years, were less efficient in both resisting phages and killing protists. Moreover, chronic isolates showed reduced killing of wax moth larvae (Galleria mellonella probably due to weaker in vitro growth and protease expression. These results suggest that P. aeruginosa long-term adaptation to CF-lungs could trade off with its survival in aquatic environmental reservoirs in the presence of microbial enemies, while lowered virulence could reduce pathogen opportunities to infect insect vectors; factors that are both likely to result in poorer environmental transmission. From an applied perspective, phage therapy could be useful against chronic P. aeruginosa lung infections that are often characterized by multidrug resistance: chronic isolates were least resistant to phages and their poor growth will likely slow down the emergence of beneficial resistance mutations.

  19. Pseudomonas aeruginosa adaptation to lungs of cystic fibrosis patients leads to lowered resistance to phage and protist enemies.

    Science.gov (United States)

    Friman, Ville-Petri; Ghoul, Melanie; Molin, Søren; Johansen, Helle Krogh; Buckling, Angus

    2013-01-01

    Pathogenic life styles can lead to highly specialized interactions with host species, potentially resulting in fitness trade-offs in other ecological contexts. Here we studied how adaptation of the environmentally transmitted bacterial pathogen, Pseudomonas aeruginosa, to cystic fibrosis (CF) patients affects its survival in the presence of natural phage (14/1, ΦKZ, PNM and PT7) and protist (Tetrahymena thermophila and Acanthamoebae polyphaga) enemies. We found that most of the bacteria isolated from relatively recently intermittently colonised patients (1-25 months), were innately phage-resistant and highly toxic for protists. In contrast, bacteria isolated from long time chronically infected patients (2-23 years), were less efficient in both resisting phages and killing protists. Moreover, chronic isolates showed reduced killing of wax moth larvae (Galleria mellonella) probably due to weaker in vitro growth and protease expression. These results suggest that P. aeruginosa long-term adaptation to CF-lungs could trade off with its survival in aquatic environmental reservoirs in the presence of microbial enemies, while lowered virulence could reduce pathogen opportunities to infect insect vectors; factors that are both likely to result in poorer environmental transmission. From an applied perspective, phage therapy could be useful against chronic P. aeruginosa lung infections that are often characterized by multidrug resistance: chronic isolates were least resistant to phages and their poor growth will likely slow down the emergence of beneficial resistance mutations.

  20. The evolution and adaptation of clinical Pseudomonas aeruginosa isolates from early cystic fibrosis infections

    DEFF Research Database (Denmark)

    Lindegaard, Mikkel

    Pseudomonas aeruginosa is a major cause of morbidity and mortality in cystic fibrosis (CF) patients. P. aeruginosa infects the CF airways and establishes chronic infections that can last for a lifetime during which P.aeruginosa evolves in order to adapt to the environment.In this PhD thesis, we...

  1. Garlic blocks quorum sensing and promotes rapid clearing of pulmonary Pseudomonas aeruginosa infections

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas; Jensen, Peter Østrup; Rasmussen, Thomas B

    2005-01-01

    to otherwise lethal doses of antibiotics, and protects against the bactericidal activity of polymorphonuclear leukocytes (PMNs). It has been previously demonstrated that QS is inhibited by garlic extract. In this study, the synergistic effects of garlic and tobramycin, and PMNs activities have been evaluated....... P. aeruginosa was grown in vitro in continuous-culture once-through flow chambers with and without garlic extract. The garlic-treated biofilms were susceptible to both tobramycin and PMN grazing. Furthermore, the PMNs showed an increase in respiratory burst activation, when incubated with the garlic......-treated biofilm. Garlic extract was administered as treatment for a mouse pulmonary infection model. Mice were treated with garlic extract or placebo for 7 days, with the initial 2 days being prophylactic before P. aeruginosa was instilled in the left lung of the mice. Bacteriology, mortality, histopathology...

  2. PFGE and antibiotic susceptibility phenotype analysis of Pseudomonas aeruginosa strain chronically infecting Cystic Fibrosis patients

    Directory of Open Access Journals (Sweden)

    Giovanna Pulcrano

    2008-09-01

    Full Text Available Pseudomonas aeruginosa is the leading cause of chronic lung infection and following pulmonary worsening of cystic fibrosis patients. To verify whether bacterial modifications regarding motility, mucoidy, and serum susceptibility proceeded from an adaptation to chronic infection or a replacement with a new strain, sequential P. aeruginosa isolates of known phenotype collected from 5 cystic fibrosis patients were typed by pulsed-field gel electophoresis (PFGE. Antimicrobial susceptibility testing of all isolates was performed by the disc diffusion method. PFGE typing demonstrated that strains dissimilar in colony morphotype and of different antibiotic susceptibility patterns could be of the same genotype. Some patients were colonized with a rather constant P. aeruginosa flora, with strains of different phenotypes but of one genotype. Instead, some patients may be colonized by more than one genotype. Secretion of mucoid exopolysaccharide and acquisition of a new antibiotic susceptibility phenotype in these strain appear to evolve during chronic colonization in cystic fibrosis patients from specific adaptation to infection rather than from acquisition of new bacterial strains.

  3. Fitness of isogenic colony morphology variants of Pseudomonas aeruginosa in murine airway infection.

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    Elza Rakhimova

    Full Text Available Chronic lung infections with Pseudomonas aeruginosa are associated with the diversification of the persisting clone into niche specialists and morphotypes, a phenomenon called 'dissociative behaviour'. To explore the potential of P. aeruginosa to change its morphotype by single step loss-of-function mutagenesis, a signature-tagged mini-Tn5 plasposon library of the cystic fibrosis airway isolate TBCF10839 was screened for colony morphology variants under nine different conditions in vitro. Transposon insertion into 1% of the genome changed colony morphology into eight discernable morphotypes. Half of the 55 targets encode features of primary or secondary metabolism whereby quinolone production was frequently affected. In the other half the transposon had inserted into genes of the functional categories transport, regulation or motility/chemotaxis. To mimic dissociative behaviour of isogenic strains in lungs, pools of 25 colony morphology variants were tested for competitive fitness in an acute murine airway infection model. Six of the 55 mutants either grew better or worse in vivo than in vitro, respectively. Metabolic proficiency of the colony morphology variant was a key determinant for survival in murine airways. The most common morphotype of self-destructive autolysis did unexpectedly not impair fitness. Transposon insertions into homologous genes of strain PAO1 did not reproduce the TBCF10839 mutant morphotypes for 16 of 19 examined loci pointing to an important role of the genetic background on colony morphology. Depending on the chosen P. aeruginosa strain, functional genome scans will explore other areas of the evolutionary landscape. Based on our discordant findings of mutant phenotypes in P. aeruginosa strains PAO1, PA14 and TBCF10839, we conclude that the current focus on few reference strains may miss modes of niche adaptation and dissociative behaviour that are relevant for the microevolution of complex traits in the wild.

  4. Chronic Pseudomonas aeruginosa infection definition: EuroCareCF Working Group report

    DEFF Research Database (Denmark)

    Pressler, T; Bohmova, C; Conway, S;

    2011-01-01

    Chronic pulmonary infection with P. aeruginosa develops in most patients with cystic fibrosis (CF); by adulthood 80% of patients are infected and chronic P. aeruginosa infection is the primary cause of increased morbidity and mortality in CF. Chronic infection is preceded by an intermittent stage...

  5. 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.

  6. The Role of Exoenzyme S in Pseudomonas aeruginosa Infections

    Science.gov (United States)

    1988-12-20

    I1T-To FrIE MNP AD______ I. 10 00 THE ROLE OF EXOENZYME S IN PSEUDOMONAS AERUGINOSA INFECTIONS Ln 0 CNFINAL REPORT I BARBARA H. IGLEWSKI DARA W...well to the enzyme neutralization titers. Second, healthy individuals or patients infected with species other than P. aeruglnosa had either no/or low...fusions, a total of 8 stable clones were isolated and recloned. All 8 monoclonal antibodies reacted with S in Western blots, and 5 neutralized S enzyme

  7. Bacteriophages for the treatment of Pseudomonas aeruginosa infections.

    Science.gov (United States)

    Harper, D R; Enright, M C

    2011-07-01

    Bacteriophages were first identified in 1915 and were used as antimicrobial agents from 1919 onwards. Despite apparent successes and widespread application, early users did not understand the nature of these agents and their efficacy remained controversial. As a result, they were replaced in the west by chemical antibiotics once these became available. However, bacteriophages remained a common therapeutic approach in parts of Eastern Europe where they are still in use. Increasing levels of antibiotic-resistant bacterial infections are now driving demand for novel therapeutic approaches. In cases where antibiotic options are limited or nonexistent, the pressure for new agents is greatest. One of the most prominent areas of concern is multidrug-resistant Gram-negative bacteria. Pseudomonas aeruginosa is a prominent member of this class and is the cause of damaging infections that can be resistant to successful treatment with conventional antibiotics. At the same time, it exhibits a number of properties that make it a suitable target for bacteriophage-based approaches, including growth in biofilms that can hydrolyse following phage infection. Pseudomonas aeruginosa provides a striking example of an infection where clinical need and the availability of a practical therapy coincide.

  8. Pseudomonas aeruginosa forms Biofilms in Acute InfectionIndependent of Cell-to-Cell Signaling

    Energy Technology Data Exchange (ETDEWEB)

    Schaber, J. Andy; Triffo, W.J.; Suh, Sang J.; Oliver, Jeffrey W.; Hastert, Mary C.; Griswold, John A.; Auer, Manfred; Hamood, Abdul N.; Rumbaugh, Kendra P.

    2006-09-20

    Biofilms are bacterial communities residing within a polysaccharide matrix that are associated with persistence and antibiotic resistance in chronic infections. We show that the opportunistic pathogen Pseudomonas aeruginosa forms biofilms within 8 hours of infection in thermally-injured mice, demonstrating that biofilms contribute to bacterial colonization in acute infections. P. aeruginosa biofilms were visualized within burned tissue surrounding blood vessels and adipose cells. Although quorum sensing (QS), a bacterial signaling mechanism, coordinates differentiation of biofilms in vitro, wild type and QS-deficient P. aeruginosa formed similar biofilms in vivo. Our findings demonstrate that P. aeruginosa forms biofilms on specific host tissues independent of QS.

  9. Pseudomonas aeruginosa Alginate Overproduction Promotes Coexistence with Staphylococcus aureus in a Model of Cystic Fibrosis Respiratory Infection

    Science.gov (United States)

    Limoli, Dominique H.; Whitfield, Gregory B.; Kitao, Tomoe; Ivey, Melissa L.; Davis, Michael R.; Grahl, Nora; Hogan, Deborah A.; Rahme, Laurence G.; Howell, P. Lynne

    2017-01-01

    ABSTRACT While complex intra- and interspecies microbial community dynamics are apparent during chronic infections and likely alter patient health outcomes, our understanding of these interactions is currently limited. For example, Pseudomonas aeruginosa and Staphylococcus aureus are often found to coinfect the lungs of patients with cystic fibrosis (CF), yet these organisms compete under laboratory conditions. Recent observations that coinfection correlates with decreased health outcomes necessitate we develop a greater understanding of these interbacterial interactions. In this study, we tested the hypothesis that P. aeruginosa and/or S. aureus adopts phenotypes that allow coexistence during infection. We compared competitive interactions of P. aeruginosa and S. aureus isolates from mono- or coinfected CF patients employing in vitro coculture models. P. aeruginosa isolates from monoinfected patients were more competitive toward S. aureus than P. aeruginosa isolates from coinfected patients. We also observed that the least competitive P. aeruginosa isolates possessed a mucoid phenotype. Mucoidy occurs upon constitutive activation of the sigma factor AlgT/U, which regulates synthesis of the polysaccharide alginate and dozens of other secreted factors, including some previously described to kill S. aureus. Here, we show that production of alginate in mucoid strains is sufficient to inhibit anti-S. aureus activity independent of activation of the AlgT regulon. Alginate reduces production of siderophores, 2-heptyl-4-hydroxyquinolone-N-oxide (HQNO), and rhamnolipids—each required for efficient killing of S. aureus. These studies demonstrate alginate overproduction may be an important factor driving P. aeruginosa coinfection with S. aureus. PMID:28325763

  10. Clinical and Morphological Studies on Spontaneous Cases of Pseudomonas aeruginosa Infections in Birds

    Directory of Open Access Journals (Sweden)

    I Dinev1, S Denev2* and G Beev2

    2013-07-01

    Full Text Available Clinical, pathoanatomical, histological, and bacteriological studies were performed on broiler chickens, growing broiler parents, and growing egg layers, in three different poultry farms, after an outbreak of Pseudomonas aeruginosa infections. The method of contamination of the birds was established. Several local and systemic clinico-morphological forms of spontaneous P. aeruginosa infections in various categories of stock birds were described: cases of P. aeruginosa infection resulting from injection of contaminated vaccines; case of P. aeruginosa infections through contaminated aerosol vaccine and cases of pododermatitis, periarthritis and arthritis in broiler chickens associated with P. aeruginosa infection. In different cases mortality range between 0.5 and 50%. The results showed that apart from embryonic mortality in hatcheries, and septicemic infections in newly hatched chickens, the pathogenicity of P. aeruginosa was associated with localized and systemic lesions in this category, as well as in young and growing birds. On one hand, these results have a theoretical significance, contributing for the confirmation and expansion of the wide array of clinico-morphological forms of P. aeruginosa infections in birds. On the other hand, the knowledge on these forms has a purely practical significance in the diagnostics of P. aeruginosa infections by poultry pathologists and veterinary practitioners.

  11. Pseudomonas aeruginosa biofilm infections in cystic fibrosis: insights into pathogenic processes and treatment strategies

    DEFF Research Database (Denmark)

    Hassett, Daniel J; Korfhagen, Thomas R; Irvin, Randall T;

    2010-01-01

    CF airway mucus can be infected by opportunistic microorganisms, notably Pseudomonas aeruginosa. Once organisms are established as biofilms, even the most potent antibiotics have little effect on their viability, especially during late-stage chronic infections. Better understanding of the mechani...... of the mechanisms used by P. aeruginosa to circumvent host defenses and therapeutic intervention strategies is critical for advancing novel treatment strategies....

  12. Respiratory syncytial virus infection facilitates acute colonization of Pseudomonas aeruginosa in mice

    DEFF Research Database (Denmark)

    de Vrankrijker, Angélica M M; Wolfs, Tom F W; Ciofu, Oana;

    2009-01-01

    Pseudomonas aeruginosa causes opportunistic infections in immunocompromised individuals and patients ventilated mechanically and is the major pathogen in patients with cystic fibrosis, in which it causes chronic infections. Epidemiological, in vitro and animal data suggest a role for respiratory ...

  13. Pseudomonas aeruginosa Alginate Overproduction Promotes Coexistence with Staphylococcus aureus in a Model of Cystic Fibrosis Respiratory Infection.

    Science.gov (United States)

    Limoli, Dominique H; Whitfield, Gregory B; Kitao, Tomoe; Ivey, Melissa L; Davis, Michael R; Grahl, Nora; Hogan, Deborah A; Rahme, Laurence G; Howell, P Lynne; O'Toole, George A; Goldberg, Joanna B

    2017-03-21

    While complex intra- and interspecies microbial community dynamics are apparent during chronic infections and likely alter patient health outcomes, our understanding of these interactions is currently limited. For example, Pseudomonas aeruginosa and Staphylococcus aureus are often found to coinfect the lungs of patients with cystic fibrosis (CF), yet these organisms compete under laboratory conditions. Recent observations that coinfection correlates with decreased health outcomes necessitate we develop a greater understanding of these interbacterial interactions. In this study, we tested the hypothesis that P. aeruginosa and/or S. aureus adopts phenotypes that allow coexistence during infection. We compared competitive interactions of P. aeruginosa and S. aureus isolates from mono- or coinfected CF patients employing in vitro coculture models. P. aeruginosa isolates from monoinfected patients were more competitive toward S. aureus than P. aeruginosa isolates from coinfected patients. We also observed that the least competitive P. aeruginosa isolates possessed a mucoid phenotype. Mucoidy occurs upon constitutive activation of the sigma factor AlgT/U, which regulates synthesis of the polysaccharide alginate and dozens of other secreted factors, including some previously described to kill S. aureus Here, we show that production of alginate in mucoid strains is sufficient to inhibit anti-S. aureus activity independent of activation of the AlgT regulon. Alginate reduces production of siderophores, 2-heptyl-4-hydroxyquinolone-N-oxide (HQNO), and rhamnolipids-each required for efficient killing of S. aureus These studies demonstrate alginate overproduction may be an important factor driving P. aeruginosa coinfection with S. aureusIMPORTANCE Numerous deep-sequencing studies have revealed the microbial communities present during respiratory infections in cystic fibrosis (CF) patients are diverse, complex, and dynamic. We now face the challenge of determining

  14. Pseudomonas aeruginosa Dose-Response and Bathing Water Infection

    Science.gov (United States)

    Pseudomonas aeruginosa is the most commonly identified opportunistic pathogen associated with pool acquired bather disease. To better understand why this microorganism poses this protracted problem we recently appraised P. aeruginosa pool risk management. Much is known about the ...

  15. Redundant and cooperative interactions between TLR5 and NLRC4 in protective lung mucosal immunity against Pseudomonas aeruginosa.

    Science.gov (United States)

    Tolle, Leslie; Yu, Fu-shin; Kovach, Melissa A; Ballinger, Megan N; Newstead, Michael W; Zeng, Xianying; Nunez, Gabriel; Standiford, Theodore J

    2015-01-01

    Flagellin is the major structural component of flagella expressed by Pseudomonas aeruginosa (PA) and other bacteria. This protein has been shown to activate the Toll-like receptor TLR5 and the Nod-like receptor Nlrc4/Ipaf, culminating in the expression of innate cytokines and antimicrobial molecules. In this study, we tested the hypothesis that TLR5 and Nlrc4 in combination are required for maximal protective lung innate mucosal immunity against PA. To test this hypothesis, we compared innate immune responses in wild-type (WT) C57B6 mice challenged with PA intratracheally to those observed in mice genetically deficient in TLR5 (TLR5(-/-)) or Nlrc4 (Nlrc4(-/-)) alone or in combination (TLR5/Nlrc4(-/-)). As compared to WT, TLR5(-/-) and Nlrc4(-/-) mice, we observed a significant increase in mortality in TLR5/Nlrc4(-/-) mice, which was associated with a >5,000-fold increase in lung PA colony-forming units and systemic bacterial dissemination. The increased mortality observed in double-deficient mice was not attributable to differences in lung leukocyte influx or lung injury responses. Levels of biologically active IL-1β and IL-18 were reduced in the bronchoalveolar lavage fluid from PA-infected Nlrc4(-/-) and TLR5/Nlrc4(-/-) but not TLR5(-/-) mice, indicating the requirement for Nlrc4-dependent caspase-1 activation. Similarly, decreased production of biologically active IL-1β and activation of caspase-1 was observed in PA-stimulated pulmonary macrophages isolated from Nlrc4(-/-) and TLR5/Nlrc4(-/-) but not TLR5(-/-) mice, whereas the expression of iNOS and the production of NO were significantly reduced in cells from double-mutant but not single-mutant mice. Collectively, our findings indicate that TLR5 and Nlrc4 have both unique and redundant roles in lung antibacterial mucosal immunity, and the absence of both pathogen recognition receptors results in an increase in susceptibility to invasive lung infection.

  16. Multiple roles of Pseudomonas aeruginosa TBCF10839 PilY1 in motility, transport and infection

    DEFF Research Database (Denmark)

    Bohn, Yu-Sing Tammy; Brandes, Gudrun; Rakhimova, Elza

    2009-01-01

    Polymorphonuclear neutrophils are the most important mammalian host defence cells against infections with Pseudomonas aeruginosa. Screening of a signature tagged mutagenesis library of the non-piliated P. aeruginosa strain TBCF10839 uncovered that transposon inactivation of its pilY1 gene rendere...

  17. Complete Genome Sequence of Pseudomonas aeruginosa Podophage MPK7, Which Requires Type IV Pili for Infection.

    Science.gov (United States)

    Bae, Hee-Won; Cho, You-Hee

    2013-10-10

    We report the complete genome sequence of Pseudomonas aeruginosa podophage MPK7. It displays synteny to the P. aeruginosa phages of the Phikmvlikevirus genus, which includes phiKMV and LKA1. MPK7 requires type IV pili (TFP) for infection, suggesting the role of functional TFP as the receptor for this phage genus.

  18. Selective eicosanoid-generating capacity of cytoplasmic phospholipase A2 in Pseudomonas aeruginosa-infected epithelial cells.

    Science.gov (United States)

    Hurley, Bryan P; Pirzai, Waheed; Mumy, Karen L; Gronert, Karsten; McCormick, Beth A

    2011-02-01

    Airway neutrophil infiltration is a pathological hallmark observed in multiple lung diseases including pneumonia and cystic fibrosis. Bacterial pathogens such as Pseudomonas aeruginosa instigate neutrophil recruitment to the air space. Excessive accumulation of neutrophils in the lung often contributes to tissue destruction. Previous studies have unveiled hepoxilin A(3) as the key molecular signal driving neutrophils across epithelial barriers. The eicosanoid hepoxilin A(3) is a potent neutrophil chemoattractant produced by epithelial cells in response to infection with P. aeruginosa. The enzyme phospholipase A(2) liberates arachidonic acid from membrane phospholipids, the rate-limiting step in the synthesis of all eicosanoids, including hepoxilin A(3). Once generated, aracidonic acid is acted upon by multiple cyclooxygenases and lipoxygenases producing an array of functionally diverse eicosanoids. Although there are numerous phospholipase A(2) isoforms capable of generating arachidonic acid, the isoform most often associated with eicosanoid generation is cytoplasmic phospholipase A(2)α. In the current study, we observed that the cytoplasmic phospholipase A(2)α isoform is required for mediating P. aeruginosa-induced production of certain eicosanoids such as prostaglandin E(2). However, we found that neutrophil transepithelial migration induced by P. aeruginosa does not require cytoplasmic phospholipase A(2)α. Furthermore, P. aeruginosa-induced hepoxilin A(3) production persists despite cytoplasmic phospholipase A(2)α suppression and generation of the 12-lipoxygenase metabolite 12-HETE is actually enhanced in this context. These results suggest that alterative phospholipase A(2) isoforms are utilized to synthesize 12-lipoxygenase metabolites. The therapeutic implications of these findings are significant when considering anti-inflammatory therapies based on targeting eicosanoid synthesis pathways.

  19. Granulocyte-macrophage colony stimulatory factor enhances the pro-inflammatory response of interferon-γ-treated macrophages to Pseudomonas aeruginosa infection.

    Directory of Open Access Journals (Sweden)

    Sonali Singh

    Full Text Available Pseudomonas aeruginosa is an opportunistic pathogen that can cause severe infections at compromised epithelial surfaces, such those found in burns, wounds, and in lungs damaged by mechanical ventilation or recurrent infections, particularly in cystic fibrosis (CF patients. CF patients have been proposed to have a Th2 and Th17-biased immune response suggesting that the lack of Th1 and/or over exuberant Th17 responses could contribute to the establishment of chronic P. aeruginosa infection and deterioration of lung function. Accordingly, we have observed that interferon (IFN-γ production by peripheral blood mononuclear cells from CF patients positively correlated with lung function, particularly in patients chronically infected with P. aeruginosa. In contrast, IL-17A levels tended to correlate negatively with lung function with this trend becoming significant in patients chronically infected with P. aeruginosa. These results are in agreement with IFN-γ and IL-17A playing protective and detrimental roles, respectively, in CF. In order to explore the protective effect of IFN-γ in CF, the effect of IFN-γ alone or in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF, on the ability of human macrophages to control P. aeruginosa growth, resist the cytotoxicity induced by this bacterium or promote inflammation was investigated. Treatment of macrophages with IFN-γ, in the presence and absence of GM-CSF, failed to alter bacterial growth or macrophage survival upon P. aeruginosa infection, but changed the inflammatory potential of macrophages. IFN-γ caused up-regulation of monocyte chemoattractant protein-1 (MCP-1 and TNF-α and down-regulation of IL-10 expression by infected macrophages. GM-CSF in combination with IFN-γ promoted IL-6 production and further reduction of IL-10 synthesis. Comparison of TNF-α vs. IL-10 and IL-6 vs. IL-10 ratios revealed the following hierarchy in regard to the pro-inflammatory potential of human

  20. Onset of persistent pseudomonas aeruginosa infection in children with cystic fibrosis with interval censored data

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    Wenjie Wang

    2016-09-01

    Full Text Available Abstract Background Persistent Pseudomonas aeruginosa (PPA infection promotes lung function deterioration in children with cystic fibrosis (CF. Although early CF diagnosis through newborn screening (NBS has been shown to provide nutritional/growth benefit, it is unclear whether NBS lowers the risk of PPA infection and how the effect of NBS vary with age. Modeling the onset age of PPA infection is challenging because 1 the onset age of PPA infection is interval censored in patient registry data; and 2 some risk factors such as NBS may have time-varying effects. Methods This problem fits into the framework of a recently developed Bayesian dynamic Cox model for interval censored data, where each regression coefficient is allowed to be time-varying to an extent determined by the data. Results Application of the methodology to data from the CF Foundation Patient Registry revealed interesting findings. Compared with patients with meconium ileus or diagnosed through signs or symptoms, patients diagnosed through NBS had significantly lower risks of acquiring PPA infection between age 1 and 2 years, and the benefit in survival rate was found to last up to age 4 years. Two cohorts of five years apart were compared. Patients born in cohort 2003–2004 had significantly lower risks of the PPA infections at any age up to 4 years than those born in 1998–1999. Conclusions The study supports benefits of NBS on PPA infection in early childhood. In addition, our analyses demonstrate that patients in the more recent cohort had significantly lower risks of acquiring PPA infection up to age 4 years, which suggests improved CF treatment and care over time.

  1. Pseudo-outbreak of pseudomonas aeruginosa in HIV-infected patients undergoing fiberoptic bronchoscopy

    DEFF Research Database (Denmark)

    Kolmos, H J; Lerche, A; Kristoffersen, Kirsten Lydia;

    1994-01-01

    Pseudomonas aeruginosa was isolated from bronchoalveolar lavage fluid from 8 consecutive patients undergoing bronchoscopy at an infectious diseases unit. None of the patients developed signs of respiratory tract infection that could be ascribed to the organism. The source of contamination...

  2. Mucoid conversion of Pseudomonas aeruginosa by hydrogen peroxide: a mechanism for virulence activation in the cystic fibrosis lung

    DEFF Research Database (Denmark)

    Mathee, K; Ciofu, O; Sternberg, C

    1999-01-01

    The leading cause of mortality in patients with cystic fibrosis (CF) is respiratory failure due in large part to chronic lung infection with Pseudomonas aeruginosa strains that undergo mucoid conversion, display a biofilm mode of growth in vivo and resist the infiltration of polymorphonuclear...... of alginate, (ii) exhibited no detectable differences in growth rate, (iii) showed an unaltered LPS profile, (iv) were approximately 72% reduced in the amount of inducible-beta-lactamase and (v) secreted little or no LasA protease and only showed 44% elastase activity. A characteristic approximately 54 k....... These findings indicate that gene activation in bacteria by toxic oxygen radicals, similar to that found in plants and mammalian cells, may serve as a defence mechanism for the bacteria. This suggests that mucoid conversion is a response to oxygen radical exposure and that this response is a mechanism of defence...

  3. Mucoid conversion of Pseudomonas aeruginosa by hydrogen peroxide: a mechanism for virulence activation in the cystic fibrosis lung

    DEFF Research Database (Denmark)

    Mathee, Kalai; Ciofu, Oana; Sternberg, Claus

    1999-01-01

    The leading cause of mortality in patients with cystic fibrosis (CF) is respiratory failure due in large part to chronic lung infection with Pseudomonas aeruginosa strains that undergo mucoid conversion, display a biofilm mode of growth in vivo and resist the infiltration of polymorphonuclear......) exhibited no detectable differences in growth rate, (iii) showed an unaltered LPS profile, (iv) were similar to 72% reduced in the amount of inducible-beta-lactamase and (v) secreted little or Department of Clinical no LasA protease and only showed 44% elastase activity. A characteristic similar to 54 k....... These findings indicate that gene activation in bacteria by toxic oxygen radicals, similar to that found in plants and mammalian cells, may serve as a defence mechanism for the bacteria. This suggests that mucoid conversion is a response to oxygen radical exposure and that this response is a mechanism of defence...

  4. Secretory IgA as a diagnostic tool for Pseudomonas aeruginosa respiratory colonization

    DEFF Research Database (Denmark)

    Aanaes, Kasper; Johansen, Helle Krogh; Poulsen, Steen Seier;

    2012-01-01

    BACKGROUND: Pseudomonas aeruginosa sinusitis may be the focus for intermittent lung colonization in patients with cystic fibrosis (CF). The sinusitis may induce elevated IgA levels in nasal secretion and saliva against P. aeruginosa. METHODS: 120 CF patients chronically infected, intermittently...... secretions and saliva than those without P. aeruginosa in the lungs, indicating that P. aeruginosa sinusitis may precede intermittent colonization and chronic infection of the lungs. CONCLUSIONS: Specific IgA against P. aeruginosa in nasal secretions and saliva can contribute to differentiation between...

  5. Pseudomonas aeruginosa in a neonatal intensive care unit: molecular epidemiology and infection control measures

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    Triassi Maria

    2009-05-01

    Full Text Available Abstract Background Pseudomonas aeruginosa, a non-fermentative, gram-negative rod, is responsible for a wide variety of clinical syndromes in NICU patients, including sepsis, pneumonia, meningitis, diarrhea, conjunctivitis and skin infections. An increased number of infections and colonisations by P. aeruginosa has been observed in the neonatal intensive care unit (NICU of our university hospital between 2005 and 2007. Methods Hand disinfection compliance before and after an educational programme on hand hygiene was evaluated. Identification of microrganisms was performed using conventional methods. Antibiotic susceptibility was evaluated by MIC microdilution. Genotyping was performed by PFGE analysis. Results The molecular epidemiology of Pseudomonas aeruginosa in the NICU of the Federico II University hospital (Naples, Italy and the infection control measures adopted to stop the spreading of P. aeruginosa in the ward were described. From July 2005 to June 2007, P. aeruginosa was isolated from 135 neonates and caused severe infections in 11 of them. Macrorestriction analysis of clinical isolates from 90 neonates identified 20 distinct genotypes, one major PFGE type (A being isolated from 48 patients and responsible for 4 infections in 4 of them, four other distinct recurrent genotypes being isolated in 6 to 4 patients. Seven environmental strains were isolated from the hand of a nurse and from three sinks on two occasions, two of these showing PFGE profiles A and G identical to two clinical isolates responsible for infection. The successful control of the outbreak was achieved through implementation of active surveillance of healthcare-associated infections in the ward together with environmental microbiological sampling and an intense educational programme on hand disinfection among the staff members. Conclusion P. aeruginosa infections in the NICU were caused by the cross-transmission of an epidemic clone in 4 neonates, and by the selection

  6. Cathelicidin host defence peptide augments clearance of pulmonary Pseudomonas aeruginosa infection by its influence on neutrophil function in vivo.

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    Paula E Beaumont

    Full Text Available Cathelicidins are multifunctional cationic host-defence peptides (CHDP; also known as antimicrobial peptides and an important component of innate host defence against infection. In addition to microbicidal potential, these peptides have properties with the capacity to modulate inflammation and immunity. However, the extent to which such properties play a significant role during infection in vivo has remained unclear. A murine model of acute P. aeruginosa lung infection was utilised, demonstrating cathelicidin-mediated enhancement of bacterial clearance in vivo. The delivery of exogenous synthetic human cathelicidin LL-37 was found to enhance a protective pro-inflammatory response to infection, effectively promoting bacterial clearance from the lung in the absence of direct microbicidal activity, with an enhanced early neutrophil response that required both infection and peptide exposure and was independent of native cathelicidin production. Furthermore, although cathelicidin-deficient mice had an intact early cellular inflammatory response, later phase neutrophil response to infection was absent in these animals, with significantly impaired clearance of P. aeruginosa. These findings demonstrate the importance of the modulatory properties of cathelicidins in pulmonary infection in vivo and highlight a key role for cathelicidins in the induction of protective pulmonary neutrophil responses, specific to the infectious milieu. In additional to their physiological roles, CHDP have been proposed as future antimicrobial therapeutics. Elucidating and utilising the modulatory properties of cathelicidins has the potential to inform the development of synthetic peptide analogues and novel therapeutic approaches based on enhancing innate host defence against infection with or without direct microbicidal targeting of pathogens.

  7. Role of ppGpp in Pseudomonas aeruginosa acute pulmonary infection and virulence regulation.

    Science.gov (United States)

    Xu, Xiaohui; Yu, Hua; Zhang, Di; Xiong, Junzhi; Qiu, Jing; Xin, Rong; He, Xiaomei; Sheng, Halei; Cai, Wenqiang; Jiang, Lu; Zhang, Kebin; Hu, Xiaomei

    2016-11-01

    During infection, bacteria might generate adaptive responses to facilitate their survival and colonization in the host environment. The alarmone guanosine 5'-triphosphate-3'-diphosphate (ppGpp), the levels of which are regulated by the RelA and SpoT enzymes, plays a critical role in mediating bacterial adaptive responses and virulence. However, the mechanism by which ppGpp regulates virulence-associated traits in Pseudomonas aeruginosa is poorly understood. To investigate the regulatory role of ppGpp, the ppGpp-deficient strain ΔRS (relA and spoT gene double mutant) and the complemented strain ΔRS(++) (complemented with relA and spoT genes) were constructed. Herein, we reported that the ΔRS strain showed decreased cytotoxicity towards A549 human alveolar adenocarcinoma cell lines and led to reduced mortality, lung edema and inflammatory cell infiltration in a mouse model of acute pneumonia compared to wild-type PAO1 and the complemented strain ΔRS(++). Subsequent analyses demonstrated that the ΔRS strain displayed reduced T3SS expression, decreased levels of elastase activity, pyocyanin, pyoverdin and alginate, and inhibited swarming and biofilm formation compared to PAO1 and the complemented strain ΔRS(++). In addition, the results demonstrate that ppGpp-mediated regulation of T3SS, virulence factor production, and swarming occurs in a quinolone quorum-sensing system-dependent manner. Taken together, these results suggest that ppGpp is required for virulence regulation in P. aeruginosa, providing new clues for the development of interference strategies against bacterial infection.

  8. Protective effect of DNA vaccine encoding pseudomonas exotoxin A and PcrV against acute pulmonary P. aeruginosa Infection.

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    Mingzi Jiang

    Full Text Available Infections with Pseudomonas aeruginosa have been a long-standing challenge for clinical therapy because of complex pathogenesis and resistance to antibiotics, thus attaching importance to explore effective vaccines for prevention and treatment. In the present study, we constructed a novel DNA vaccine by inserting mutated gene toxAm encoding Pseudomonas Exotoxin A and gene pcrV encoding tip protein of the type III secretion system into respective sites of a eukaryotic plasmid pIRES, named pIRES-toxAm-pcrV, and next evaluated the efficacy of the vaccine in murine acute Pseudomonas pneumonia models. Compared to DNA vaccines encoding single antigen, mice vaccinated with pIRES-toxAm-pcrV elicited higher levels of antigen-specific serum immunoglobulin G (IgG, enhanced splenic cell proliferation and cytokine secretion in response to Pseudomonas aeruginosa antigens, additionally PAO1 challenge in mice airway resulted in reduced bacteria burden and milder pathologic changes in lungs. Besides, it was observed that immunogenicity and protection could be promoted by the CpG ODN 1826 adjuvant. Taken together, it's revealed that recombinant DNA vaccine pIRES-toxAm-pcrV was a potential candidate for immunotherapy of Pseudomonas aeruginosa infection and the CpG ODN 1826 a potent stimulatory adjuvant for DNA vaccination.

  9. Polymorphonuclear leukocytes restrict growth of Pseudomonas aeruginosa in the lungs of cystic fibrosis patients

    DEFF Research Database (Denmark)

    Kragh, Kasper Nørskov; Alhede, Morten; Jensen, Peter Ø.;

    2014-01-01

    in a mouse model. The growth rate of P. aeruginosa within CF lungs did not correlate with the dimensions of bacterial aggregates but showed an inverse correlation to the concentration of polymorphonuclear leukocytes (PMNs) surrounding the bacteria. A growth-limiting effect on P. aeruginosa by PMNs was also...... PMNs slow the growth of the bacteria and render them less susceptible to antibiotic treatment while enabling them to persist by anaerobic respiration....

  10. Drosophila melanogaster as an animal model for the study of Pseudomonas aeruginosa biofilm infections in vivo.

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    Heidi Mulcahy

    2011-10-01

    Full Text Available Pseudomonas aeruginosa is an opportunistic pathogen capable of causing both acute and chronic infections in susceptible hosts. Chronic P. aeruginosa infections are thought to be caused by bacterial biofilms. Biofilms are highly structured, multicellular, microbial communities encased in an extracellular matrix that enable long-term survival in the host. The aim of this research was to develop an animal model that would allow an in vivo study of P. aeruginosa biofilm infections in a Drosophila melanogaster host. At 24 h post oral infection of Drosophila, P. aeruginosa biofilms localized to and were visualized in dissected Drosophila crops. These biofilms had a characteristic aggregate structure and an extracellular matrix composed of DNA and exopolysaccharide. P. aeruginosa cells recovered from in vivo grown biofilms had increased antibiotic resistance relative to planktonically grown cells. In vivo, biofilm formation was dependent on expression of the pel exopolysaccharide genes, as a pelB::lux mutant failed to form biofilms. The pelB::lux mutant was significantly more virulent than PAO1, while a hyperbiofilm strain (PAZHI3 demonstrated significantly less virulence than PAO1, as indicated by survival of infected flies at day 14 postinfection. Biofilm formation, by strains PAO1 and PAZHI3, in the crop was associated with induction of diptericin, cecropin A1 and drosomycin antimicrobial peptide gene expression 24 h postinfection. In contrast, infection with the non-biofilm forming strain pelB::lux resulted in decreased AMP gene expression in the fly. In summary, these results provide novel insights into host-pathogen interactions during P. aeruginosa oral infection of Drosophila and highlight the use of Drosophila as an infection model that permits the study of P. aeruginosa biofilms in vivo.

  11. Pseudomonas aeruginosa Ventilator-Associated Pneumonia Induces Lung Injury through TNF-α/c-Jun NH2-Terminal Kinase Pathways

    Science.gov (United States)

    Hsu, Ching-Mei

    2017-01-01

    Ventilator-associated pneumonia (VAP) is a common nosocomial infection among intensive care unit (ICU) patients. Pseudomonas aeruginosa (PA) is the most common multidrug-resistant Gram-negative pathogen and VAP caused by PA carries a high rate of morbidity and mortality. This study examined the molecular mechanism of PA VAP-induced lung injury. C57BL/6 wild-type (WT) mice and JNK1 knockout (JNK1-/-) mice received mechanical ventilation (MV) for 3 h at 2 days after receiving nasal instillation of PA. The WT and JNK1-/- mice also received MV after the induction of lung injury by instillation of supernatants from PA-stimulated alveolar macrophages (AMs). AMs isolated from WT, IκB-kinase (IKK)βΔMye (IKKβ was selectively deleted in macrophages), and JNK1-/- mice were ex vivo stimulated with live PA and supernatants were collected for cytokine assay. Intranasal instillation of 106 PA enhanced MV-induced NF-κB DNA binding activity in the lungs and nitrite levels in BALF. MV after PA instillation significantly increased the expression of ICAM and VCAM in the lungs and TNF-α, IL-1β, and IL-6 levels in bronchoalveolar lavage fluid (BALF) of WT mice, but not in JNK1-/- mice. MV after supernatant instillation induced more total protein concentration in BALF and neutrophil sequestration in the lungs in WT mice than JNK1-/- mice and cytokine assay of supernatants indicated that TNF-α is a critical regulator of PA VAP-induced lung injury. Ex vivo PA stimulation induced TNF-α production by AMs from WT as well as JNK1-/- mice but not IKKβΔMye mice. In summary, PA colonization plays an important role in PA VAP-induced lung injury through the induction of JNK1-mediated inflammation. These results suggest that the pathogenesis mechanism of PA VAP involves production of TNF-α through activation of IKK/NF-κB pathways in AMs and JNK signaling pathway in the lungs. PMID:28060857

  12. Effects of ginseng on Pseudomonas aeruginosa motility and biofilm formation

    DEFF Research Database (Denmark)

    Wu, Hong; Lee, Baoleri; Yang, Liang

    2011-01-01

    Biofilm-associated chronic Pseudomonas aeruginosa lung infections in patients with cystic fibrosis are virtually impossible to eradicate with antibiotics because biofilm-growing bacteria are highly tolerant to antibiotics and host defense mechanisms. Previously, we found that ginseng treatments......-associated chronic infections caused by P. aeruginosa....

  13. In vivo fluorescence imaging of bacteriogenic cyanide in the lungs of live mice infected with cystic fibrosis pathogens.

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    Seong-Won Nam

    Full Text Available BACKGROUND: Pseudomonas aeruginosa (PA and Burkholderia cepacia complex (Bcc, commonly found in the lungs of cystic fibrosis (CF patients, often produce cyanide (CN, which inhibits cellular respiration. CN in sputa is a potential biomarker for lung infection by CF pathogens. However, its actual concentration in the infected lungs is unknown. METHODS AND FINDINGS: This work reports observation of CN in the lungs of mice infected with cyanogenic PA or Bcc strains using a CN fluorescent chemosensor (4',5'-fluorescein dicarboxaldehyde with a whole animal imaging system. When the CN chemosensor was injected into the lungs of mice intratracheally infected with either PA or B. cepacia strains embedded in agar beads, CN was detected in the millimolar range (1.8 to 4 mM in the infected lungs. CN concentration in PA-infected lungs rapidly increased within 24 hours but gradually decreased over the following days, while CN concentration in B. cepacia-infected lungs slowly increased, reaching a maximum at 5 days. CN concentrations correlated with the bacterial loads in the lungs. In vivo efficacy of antimicrobial treatments was tested in live mice by monitoring bacteriogenic CN in the lungs. CONCLUSIONS: The in vivo imaging method was also found suitable for minimally invasive testing the efficacy of antibiotic compounds as well as for aiding the understanding of bacterial cyanogenesis in CF lungs.

  14. Characterization of bacteriophages infecting clinical isolates of Pseudomonas aeruginosa stored in a culture collection

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    C.C.S. Zanetti

    2013-08-01

    Full Text Available Some clinical isolates of Pseudomonas aeruginosa stored in our culture collection did not grow or grew poorly and showed lysis on the culture plates when removed from the collection and inoculated on MacConkey agar. One hypothesis was that bacteriophages had infected and killed those clinical isolates. To check the best storage conditions to maintain viable P. aeruginosa for a longer time, clinical isolates were stored at various temperatures and were grown monthly. We investigated the presence of phage in 10 clinical isolates of P. aeruginosa stored in our culture collection. Four strains of P. aeruginosa were infected by phages that were characterized by electron microscopy and isolated to assess their ability to infect. The best condition to maintain the viability of the strains during storage was in water at room temperature. Three Siphoviridae and two Myoviridae phages were visualized and characterized by morphology. We confirmed the presence of bacteriophages infecting clinical isolates, and their ability to infect and lyse alternative hosts. Strain PAO1, however, did not show lysis to any phage. Mucoid and multidrug resistant strains of P. aeruginosa showed lysis to 50% of the phages tested.

  15. Screening of Molecular Virulence Markers in Staphylococcus aureus and Pseudomonas aeruginosa Strains Isolated from Clinical Infections

    Science.gov (United States)

    Cotar, Ani-Ioana; Chifiriuc, Mariana-Carmen; Dinu, Sorin; Bucur, Marcela; Iordache, Carmen; Banu, Otilia; Dracea, Olguta; Larion, Cristina; Lazar, Veronica

    2010-01-01

    Staphylococcus (S.) aureus and Pseudomonas (Ps.) aeruginosa are two of the most frequently opportunistic pathogens isolated in nosocomial infections, responsible for severe infections in immunocompromised hosts. The frequent emergence of antibiotic-resistant S. aureus and Ps. aeruginosa strains has determined the development of new strategies in order to elucidate the different mechanisms used by these bacteria at different stages of the infectious process, providing the scientists with new procedures for preventing, or at least improving, the control of S. aureus and Ps. aeruginosa infections. The purpose of this study was to characterize the molecular markers of virulence in S. aureus and Ps. aeruginosa strains isolated from different clinical specimens. We used multiplex and uniplex PCR assays to detect the genes encoding different cell-wall associated and extracellular virulence factors, in order to evaluate potential associations between the presence of putative virulence genes and the outcome of infections caused by these bacteria. Our results demonstrate that all the studied S. aureus and Ps. aeruginosa strains synthesize the majority of the investigated virulence determinants, probably responsible for different types of infections. PMID:21614207

  16. Screening of Molecular Virulence Markers in Staphylococcus aureus and Pseudomonas aeruginosa Strains Isolated from Clinical Infections

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    Veronica Lazar

    2010-12-01

    Full Text Available Staphylococcus (S. aureus and Pseudomonas (Ps. aeruginosa are two of the most frequently opportunistic pathogens isolated in nosocomial infections, responsible for severe infections in immunocompromised hosts. The frequent emergence of antibiotic-resistant S. aureus and Ps. aeruginosa strains has determined the development of new strategies in order to elucidate the different mechanisms used by these bacteria at different stages of the infectious process, providing the scientists with new procedures for preventing, or at least improving, the control of S. aureus and Ps. aeruginosa infections. The purpose of this study was to characterize the molecular markers of virulence in S. aureus and Ps. aeruginosa strains isolated from different clinical specimens. We used multiplex and uniplex PCR assays to detect the genes encoding different cell-wall associated and extracellular virulence factors, in order to evaluate potential associations between the presence of putative virulence genes and the outcome of infections caused by these bacteria. Our results demonstrate that all the studied S. aureus and Ps. aeruginosa strains synthesize the majority of the investigated virulence determinants, probably responsible for different types of infections.

  17. Bactericidal antibody response to Pseudomonas aeruginosa by adults with urinary tract infections.

    Science.gov (United States)

    Smalley, D L; Ourth, D D

    1979-01-01

    In this investigation we found that adults with upper urinary tract infections caused by Pseudomonas aeruginosa produced serum antibodies with bactericidal activity against the bacterium. Seventeen of 20 infected adults showed bactericidal activity with a titer range of 1:10 to 1:10,000. PMID:117024

  18. Serum concentrations of GM-CSF and G-CSF correlate with the Th1/Th2 cytokine response in cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infection

    DEFF Research Database (Denmark)

    Moser, Claus; Jensen, Peter Ø; Pressler, Tacjana;

    2005-01-01

    mobilizing monocytes and PMNs from the bone marrow, GM-CSF, G-CSF and IL-3 select subsets of dendritic cells, which subsequently induce distinct Th responses. Therefore, the present study examines the correlation between the mobilizing cytokines in serum and the Th responses. The IFN-gamma and IL-4...... lung function. In addition, an inverse correlation between IL-3 and IFN-gamma was observed. The results indicate involvement of endogenous GM-CSF, G-CSF and IL-3 in the skewed Th response in CF, and change to a Th1-dominated response might be achieved with GM-CSF treatment....

  19. Tobramycin Inhalation Powder (TIP): An Efficient Treatment Strategy for the Management of Chronic Pseudomonas Aeruginosa Infection in Cystic Fibrosis.

    Science.gov (United States)

    Lam, John; Vaughan, Steven; Parkins, Michael D

    2013-11-13

    Repeated bouts of acute and chronic lung infections are responsible for progressive pulmonary function decline in individuals with cystic fibrosis (CF), ultimately leading to respiratory failure and death. Pseudomonas aeruginosa is the archetypical CF pathogen, causes chronic infection in 70% of individuals, and is associated with an accelerated clinical decline. The management of P. aeruginosa in CF has been revolutionized with the development and widespread use of inhaled antibiotics. Aerosol delivery of antimicrobial compounds in CF enables extremely high concentrations of antibiotics to be reached directly at the site of infection potentially overcoming adaptive resistance and avoiding the potential for cumulative systemic toxicities. Tobramycin inhalation powder (TIP) represents the first dry powder inhaled (DPI) antibiotic available for use in CF. DPIs are notable for a markedly reduced time for administration, ease of portability, and increased compliance. TIP has been developed as a therapeutic alternative to tobramycin inhalation solution (TIS), the standard of care for the past 20 years within CF. Relative to TIS 300 mg nebulized twice daily in on-and-off cycles of 28 days duration, TIP 112 mg twice daily via the T-326 inhaler administered on the same schedule is associated with marked time savings, increased patient satisfaction, and comparable clinical end points. TIP represents an innovative treatment strategy for those individuals with CF and holds the promise of increased patient compliance and thus the potential for improved clinical outcomes.

  20. Multidrug resistant Pseudomonas aeruginosa infection in children undergoing chemotherapy and hematopoietic stem cell transplantation.

    Science.gov (United States)

    Caselli, Désirée; Cesaro, Simone; Ziino, Ottavio; Zanazzo, Giulio; Manicone, Rosaria; Livadiotti, Susanna; Cellini, Monica; Frenos, Stefano; Milano, Giuseppe M; Cappelli, Barbara; Licciardello, Maria; Beretta, Chiara; Aricò, Maurizio; Castagnola, Elio

    2010-09-01

    Pseudomonas aeruginosa is one leading gram-negative organism associated with nosocomial infections. Bacteremia is life-threatening in the immunocompromised host. Increasing frequency of multi-drug-resistant (MDRPA) strains is concerning. We started a retrospective survey in the pediatric hematology oncology Italian network. Between 2000 and 2008, 127 patients with Pseudomonas aeruginosa bacteremia were reported from 12 centers; 31.4% of isolates were MDRPA. Death within 30 days of a positive blood culture occurred in 19.6% (25/127) of total patients; in patients with MDRPA infection it occurred in 35.8% (14/39). In the multivariate analysis, only MDRPA had significant association with infection-related death. This is the largest series of Pseudomonas aeruginosa bacteremia cases from pediatric hematology oncology centers. Monitoring local bacterial isolates epidemiology is mandatory and will allow empiric antibiotic therapy to be tailored to reduce fatalities.

  1. Adherence of Pseudomonas aeruginosa to tracheal cells injured by influenza infection or by endotracheal intubation.

    Science.gov (United States)

    Ramphal, R; Small, P M; Shands, J W; Fischlschweiger, W; Small, P A

    1980-02-01

    Adherence of Pseudomonas aeruginosa to normal, injured, and regenerating tracheal mucosa was examined by scanning electron microscopy. Uninfected and influenza-infected murine tracheas were exposed to six strains of P. aeruginosa isolated from human sources and one strain of platn origin. All of the strains tested adhered to desquamating cells of the infected tracheas, but not to normal mucosa, the basal cell layer, or the regenerating epithelium. Adherence increased when the incubation time of the bacteria with the trachea was prolonged. Strains isolated from human tracheas appeared to adhere better than strains derived from the urinary tract. After endotracheal intubation of ferrets, P. aeruginosa adhered only to the injured cells and to areas of exposed basement membrane. We call this phenomenon "opportunistic adherence" and propose that alteration of the cell surfaces or cell injury facilitates the adherence of this bacterium and that adherence to injured cells may be a key to the pathogenesis of opportunistic Pseudomonas infections.

  2. Impact of new water systems on healthcare-associated colonization or infection with Pseudomonas aeruginosa

    Science.gov (United States)

    Lefebvre, Annick; Quantin, Catherine; Vanhems, Philippe; Lucet, Jean-Christophe; Bertrand, Xavier; Astruc, Karine; Chavanet, Pascal; Aho-Glélé, Ludwig S.

    2016-01-01

    Aim: We aimed to study the impact of new water systems, which were less contaminated with P. aeruginosa, on the incidence of healthcare-associated P. aeruginosa cases (colonizations or infections) in care units that moved to a different building between 2005 and 2014. Methods: Generalized Estimated Equations were used to compare the incidence of P. aeruginosa healthcare-associated cases according to the building. Results: Twenty-nine units moved during the study period and 2,759 cases occurred in these units. No difference was observed when the new building was compared with older buildings overall. Conclusion: Our results did not support our hypothesis of a positive association between water system contamination and the incidence of healthcare-associated P. aeruginosa cases. These results must be confirmed by linking results of water samples and patients’ data. PMID:27274443

  3. Tobramycin Inhalation Powder™: a novel drug delivery system for treating chronic Pseudomonas aeruginosa infection in cystic fibrosis.

    Science.gov (United States)

    Parkins, Michael D; Elborn, J Stuart

    2011-10-01

    Lung disease in cystic fibrosis (CF) is typified by the development of chronic airways infection culminating in bronchiectasis and progression to end-stage respiratory disease. Pseudomonas aeruginosa, a ubiquitous gram-negative bacteria, is the archetypical CF pathogen and is associated with an accelerated clinical decline. The development and widespread use of chronic suppressive aerosolized antibacterial therapies, in particular Tobramycin Inhalation Solution (TIS), in CF has contributed to reduced lung function decline and improved survival. However, the requirement for the aerosolization of these agents through nebulizers has been associated with increased treatment burden, reduced quality of life and remain a barrier to broader uptake. Tobramycin Inhalation Powder (TIP™) has been developed by Novartis with the express purpose of delivering the same benefits as TIS in a time-effective manner. Administered via the T-326™ (Novartis) Inhaler in four individual 28-mg capsules, TIP can be administered in a quarter of the time of traditional nebulizers and is inherently portable. In clinical studies, TIP has been shown to be safe, result in equivalent or superior reductions in P. aeruginosa sputum density and produce similar improvements in pulmonary function. TIP offers significant advantages in time saving, portability and convenience over traditional nebulized TIS with comparable clinical outcomes for individuals with CF.

  4. Pseudomonas aeruginosa bacteriophage PA1Ø requires type IV pili for infection and shows broad bactericidal and biofilm removal activities.

    Science.gov (United States)

    Kim, Shukho; Rahman, Marzia; Seol, Sung Yong; Yoon, Sang Sun; Kim, Jungmin

    2012-09-01

    We isolated a new lytic Pseudomonas aeruginosa phage that requires type IV pili for infection. PA1Ø has a broad bactericidal spectrum, covering Gram-positive and Gram-negative bacteria, and can eradicate biofilm cells. PA1Ø may be developed as a therapeutic agent for biofilm-related mixed infections with P. aeruginosa and Staphylococcus aureus.

  5. Tobramycin inhalation powder (TOBI Podhaler) for the treatment of lung infection in patients with cystic fibrosis.

    Science.gov (United States)

    Vazquez-Espinosa, E; Marcos, C; Alonso, T; Giron, R M; Gomez-Punter, R M; Garcia-Castillo, E; Zamora, E; Cisneros, C; Garcia, J; Valenzuela, C; Ancochea, J

    2016-01-01

    Cystic fibrosis (CF) is an autosomal recessive inherited disease secondary to a defect in the CF transmembrane conductance regulator gene (CFTR). Mortality in CF is associated with impairment of lung function in which bacterial infection plays a fundamental role. The microorganism Pseudomonas aeruginosa (P. aeruginosa) is a marker of poor prognosis. Tobramycin was the first parenteral antibiotic to be used as inhaled medication in CF. Owing to its beneficial effects; it was subsequently used in designed inhaled formulations. The first formulation was the inhalation solution, which improved lung function, lowered hospitalization rates, and reduced the courses of intravenous antibiotic. However, the high associated costs and time necessary to administer the medication negatively affected quality of life. The recent development of tobramycin inhalation powder has optimized treatment. The dry powder inhaler is a simple device that reduces administration time and improves adherence. As there is no risk of bacterial contamination, disinfection is unnecessary.

  6. A case of orbital apex syndrome due to Pseudomonas aeruginosa infection

    Directory of Open Access Journals (Sweden)

    Takeshi Kusunoki

    2011-11-01

    Full Text Available Orbital apex syndrome is commonly been thought to have a poor prognosis. Many cases of this syndrome have been reported to be caused by paranasal sinus mycosis. We encountered a very rare case (60-year-old woman of sinusitis with orbital apex syndrome due to Pseudomonas aeruginosa infection. She had received insulin and dialysis for diabtes and diabetic nephropathy, moreover anticoagulants after heart by-pass surgery. She underwent endoscopic sinus operation and was treated with antibiotics, but her loss of left vision did not improve. Recently, sinusitis cases due to Pseudomonas aeruginosa were reported to be a increasing. Therefore, we should consider the possibility of Pseudomonas aeruginosa as well as mycosis as infections of the sinus, especially inpatients who are immunocompromised body.

  7. A case of orbital apex syndrome due to Pseudomonas aeruginosa infection.

    Science.gov (United States)

    Kusunoki, Takeshi; Kase, Kaori; Ikeda, Katsuhisa

    2011-09-28

    Orbital apex syndrome is commonly been thought to have a poor prognosis. Many cases of this syndrome have been reported to be caused by paranasal sinus mycosis. We encountered a very rare case (60-year-old woman) of sinusitis with orbital apex syndrome due to Pseudomonas aeruginosa infection. She had received insulin and dialysis for diabtes and diabetic nephropathy, moreover anticoagulants after heart by-pass surgery. She underwent endoscopic sinus operation and was treated with antibiotics, but her loss of left vision did not improve. Recently, sinusitis cases due to Pseudomonas aeruginosa were reported to be a increasing. Therefore, we should consider the possibility of Pseudomonas aeruginosa as well as mycosis as infections of the sinus, especially inpatients who are immunocompromised body.

  8. Recent advances in the treatment of Pseudomonas aeruginosa infections in cystic fibrosis

    DEFF Research Database (Denmark)

    Høiby, Niels

    2011-01-01

    exacerbations and sputum density of P. aeruginosa. Other drugs such as quinolones are currently under investigation for inhalation therapy. A trial of the use of anti-Pseudomonas antibiotics for long-term prophylaxis showed no effect in patients who were not already infected. Use of azithromycin to treat CF...

  9. In vivo pharmacokinetics/pharmacodynamics of colistin and imipenem in Pseudomonas aeruginosa biofilm infection

    DEFF Research Database (Denmark)

    Hengzhuang, Wang; Wu, Hong; Ciofu, Oana;

    2012-01-01

    Many Pseudomonas aeruginosa isolates from the airways of patients with cystic fibrosis (CF) are sensitive to antibiotics in susceptibility testing, but eradication of the infection is difficult. The main reason is the biofilm formation in the airways of patients with CF. The pharmacokinetics (PKs...

  10. Evaluation of Risk Factors for Antibiotic Resistance in Patients with Nosocomial Infections Caused by Pseudomonas aeruginosa.

    Science.gov (United States)

    Sonmezer, Meliha Cagla; Ertem, Gunay; Erdinc, Fatma Sebnem; Kaya Kilic, Esra; Tulek, Necla; Adiloglu, Ali; Hatipoglu, Cigdem

    2016-01-01

    Background. Pseudomonas aeruginosa (P. aeruginosa) is resistant to various antibiotics and can cause serious nosocomial infections with high morbidity and mortality. In this clinical study, we investigated the risk factors in patients who were diagnosed with P. aeruginosa-related nosocomial infection. Methods. A retrospective case control study including patients with P. aeruginosa-related nosocomial infection. Patients who were resistant to any of the six antibiotics (imipenem, meropenem, piperacillin-tazobactam, ciprofloxacin, amikacin, and ceftazidime) constituted the study group. Results. One hundred and twenty isolates were isolated. Various risk factors were detected for each antibiotic in the univariate analysis. In the multivariate analysis, previous cefazolin use was found as an independent risk factor for the development of imipenem resistance (OR = 3.33; CI 95% [1.11-10.0]; p = 0.03), whereas previous cerebrovascular attack (OR = 3.57; CI 95% [1.31-9.76]; p = 0.01) and previous meropenem use (OR = 4.13; CI 95% [1.21-14.07]; p = 0.02) were independent factors for the development of meropenem resistance. For the development of resistance to ciprofloxacin, hospitalization in the neurology intensive care unit (OR = 4.24; CI 95% [1.5-11.98]; p = 0.006) and mechanical ventilator application (OR = 11.7; CI 95% [2.24-61.45]; p = 0.004) were independent risk factors. Conclusion. The meticulous application of contact measures can decrease the rate of nosocomial infections.

  11. Molecular epidemiology of chronic Pseudomonas aeruginosa airway infections in cystic fibrosis

    DEFF Research Database (Denmark)

    Cramer, Nina; Wiehlmann, Lutz; Ciofu, Oana

    2012-01-01

    The molecular epidemiology of the chronic airway infections with Pseudomonas aeruginosa in individuals with cystic fibrosis (CF) was investigated by cross-sectional analysis of bacterial isolates from 51 CF centers and by longitudinal analysis of serial isolates which had been collected at the CF...

  12. Pseudomonas aeruginosa tolerance to tobramycin, hydrogen peroxide and polymorphonuclear leukocytes is quorum-sensing dependent

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas; Jensen, Peter Østrup; Burmølle, Mette;

    2005-01-01

    The opportunistic human pathogen Pseudomonas aeruginosa is the predominant micro-organism of chronic lung infections in cystic fibrosis (CF) patients. P. aeruginosa colonizes the CF lungs by forming biofilm structures in the alveoli. In the biofilm mode of growth the bacteria are highly tolerant...

  13. Pseudomonas aeruginosa biofilms in the respiratory tract of cystic fibrosis patients

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas; Jensen, Peter Østrup; Fiandaca, Mark J;

    2009-01-01

    The present study was undertaken to investigate the appearance and location of Pseudomonas aeruginosa in the cystic fibrosis (CF) lung and in sputum. Samples include preserved tissues of CF patients who died due to chronic P. aeruginosa lung infection prior to the advent of intensive antibiotic...

  14. Pseudomonas aeruginosa and the in vitro and in vivo biofilm mode of growth

    DEFF Research Database (Denmark)

    Høiby, N; Krogh Johansen, H; Moser, C

    2001-01-01

    The biofilm mode of growth is the survival strategy of environmental bacteria like Pseudomonas aeruginosa. Such P. aeruginosa biofilms also occur in the lungs of chronically infected cystic fibrosis patients, where they protect the bacteria against antibiotics and the immune response. The lung...

  15. Avidity of anti-P aeruginosa antibodies during chronic infection in patients with cystic fibrosis

    DEFF Research Database (Denmark)

    Ciofu, O; Petersen, T D; Jensen, P;

    1999-01-01

    BACKGROUND: In order to study the impact on the lung function of patients with cystic fibrosis of the avidity of antipseudomonal antibodies, the avidity of antibodies against the chromosomal beta-lactamase of Pseudomonas aeruginosa (a beta ab) and against the 60-65 kDa heat shock protein of P...... function the avidity of a beta ab was higher than in patients with poor lung function (p = 0.018). No significant difference in the avidity of the anti-GroEL antibodies was observed between the two groups of patients. CONCLUSION: In patients with cystic fibrosis a high avidity of a beta ab could contribute...

  16. Fungal infections of the lung in children

    Energy Technology Data Exchange (ETDEWEB)

    Toma, Paolo; Colafati, Giovanna Stefania; D' Andrea, Maria Luisa [IRCCS Bambino Gesu Children' s Hospital, Department of Imaging, Rome (Italy); Bertaina, Alice; Mastronuzzi, Angela [IRCCS Bambino Gesu Children' s Hospital, Department of Pediatric Hematology/Oncology and Transfusion Medicine, Rome (Italy); Castagnola, Elio [IRCCS Istituto Giannina Gaslini, Department of Infective Diseases, Genoa (Italy); Finocchi, Andrea [IRCCS Bambino Gesu Children' s Hospital, Department of Pediatrics, Rome (Italy); Lucidi, Vincenzina [IRCCS Bambino Gesu Children' s Hospital, Cystic Fibrosis Center, Rome (Italy); Granata, Claudio [IRCCS Istituto Giannina Gaslini, Department of Pediatric Radiology, Genoa (Italy)

    2016-12-15

    Fungal infections of the lungs are relatively common and potentially life-threatening conditions in immunocompromised children. The role of imaging in children with lung mycosis is to delineate the extension of pulmonary involvement, to assess response to therapy, and to monitor for adverse sequelae such as bronchiectasis and cavitation. The aim of this paper is to show imaging findings in a series of patients with fungal pneumonia from two tertiary children's hospitals, to discuss differential diagnoses and to show how imaging findings can vary depending on the host immune response. (orig.)

  17. Lactic acid bacteria protect human intestinal epithelial cells from Staphylococcus aureus and Pseudomonas aeruginosa infections.

    Science.gov (United States)

    Affhan, S; Dachang, W; Xin, Y; Shang, D

    2015-12-16

    Staphylococcus aureus and Pseudomonas aeruginosa are opportunistic pathogens that cause nosocomial and food-borne infections. They promote intestinal diseases. Gastrointestinal colonization by S. aureus and P. aeruginosa has rarely been researched. These organisms spread to extra gastrointestinal niches, resulting in increasingly progressive infections. Lactic acid bacteria are Gram-positive bacteria that produce lactic acid as the major end-product of carbohydrate fermentation. These bacteria inhibit pathogen colonization and modulate the host immune response. This study aimed to investigate the effects of Lactobacillus acidophilus and Lactobacillus rhamnosus on enteric infections caused by the paradigmatic human pathogens S. aureus ATCC25923 and P. aeruginosa ATCC27853. The effect of whole cells and neutralized cell-free supernatant (CFS) of the lactobacilli on LoVo human carcinoma enterocyte (ATCC CCL-229) infection was analyzed by co-exposure, pre-exposure, and post-exposure studies. Simultaneous application of whole cells and CFS of the lactobacilli significantly eradicated enterocyte infection (P cells and CFS were added after or prior to the infection (P > 0.05). This result could be attributed to interference by extracellular polymeric substances and cell surface hydrophobicity, which resulted in the development of a pathogen that did not form colonies. Furthermore, results of the plate count and LIVE/ DEAD BacLight bacterial viability staining attributed this inhibition to a non-bacteriocin-like substance, which acted independently of organic acid and H2O2 production. Based on these results, the cell-free supernatant derived from lactobacilli was concluded to restrain the development of S. aureus and P. aeruginosa enteric infections.

  18. Homogentisate 1-2-Dioxygenase Downregulation in the Chronic Persistence of Pseudomonas aeruginosa Australian Epidemic Strain-1 in the CF Lung.

    Directory of Open Access Journals (Sweden)

    Christopher J Harmer

    Full Text Available Some Pseudomonas aeruginosa strains including Australian Epidemic Strain-1 (AES-1 or AUS-01 cause persistent chronic infection in cystic fibrosis (CF patients, with greater morbidity and mortality. Factors conferring persistence are largely unknown. Previously we analysed the transcriptomes of AES-1 grown in Luria broth, nematode growth medium for Caenorhabditis elegans assay (both aerobic and artificial sputum medium (mainly hypoxic. Transcriptional comparisons included chronic AES-1 strains against PAO1 and acute AES-1 (AES-1R against its chronic isogen (AES-1M, isolated 10.5 years apart from a CF patient and not eradicated in the meantime. Prominent amongst genes downregulated in AES-1M in all comparisons was homogentisate-1-2-dioxygenase (hmgA; an oxygen-dependent gene known to be mutationally deactivated in many chronic infection strains of P. aeruginosa. To investigate if hmgA downregulation and deactivation gave similar virulence persistence profiles, a hmgA mutant made in UCBPP-PA14 utilising RedS-recombinase and AES-1M were assessed in the C. elegans virulence assay, and the C57BL/6 mouse for pulmonary colonisation and TNF-α response. In C. elegans, hmgA deactivation resulted in significantly increased PA14 virulence while hmgA downregulation reduced AES-1M virulence. AES-1M was significantly more persistent in mouse lung and showed a significant increase in TNF-α (p<0.0001, sustained even with no detectable bacteria. PA14ΔhmgA did not show increased TNF-α. This study suggests that hmgA may have a role in P. aeruginosa persistence in chronic infection and the results provide a starting point for clarifying the role of hmgA in chronic AES-1.

  19. Cellular responses of A549 alveolar epithelial cells to serially collected Pseudomonas aeruginosa from cystic fibrosis patients at different stages of pulmonary infection

    DEFF Research Database (Denmark)

    Hawdon, Nicole A; Aval, Pouya Sadeghi; Barnes, Rebecca J;

    2010-01-01

    Pseudomonas aeruginosa is the major cause of chronic pulmonary disease in cystic fibrosis (CF) patients. During chronic infection, P. aeruginosa lose certain virulence factors, transform into a mucoid phenotype, and develop antibiotic resistance. We hypothesized that these genetic and phenotypic ...

  20. Isolated Candida infection of the lung

    Directory of Open Access Journals (Sweden)

    Yousef Shweihat

    2015-01-01

    Full Text Available Candida pneumonia is a rare infection of the lungs, with the majority of cases occurring secondary to hematological dissemination of Candida organisms from a distant site, usually the gastrointestinal tract or skin. We report a case of a 77-year-old male who is life-long smoker with a history of rheumatoid arthritis and polymyalgia rheumatica, but did not take immunosuppressants for those conditions. Here, we present an extremely rare case of isolated pulmonary parenchymal Candida infection in the form pulmonary nodules without evidence of systemic disease which has only been described in a few previous reports.

  1. High-Sensitivity Monoclonal Antibodies Specific for Homoserine Lactones Protect Mice from Lethal Pseudomonas aeruginosa Infections

    Science.gov (United States)

    Downham, Christina; Broadbent, Ian; Charlton, Keith; Porter, Andrew J.

    2014-01-01

    A number of bacteria, including pathogens like Pseudomonas aeruginosa, utilize homoserine lactones (HSLs) as quorum sensing (QS) signaling compounds and engage in cell-to-cell communication to coordinate their behavior. Blocking this bacterial communication may be an attractive strategy for infection control as QS takes a central role in P. aeruginosa biology. In this study, immunomodulation of HSL molecules by monoclonal antibodies (MAbs) was used as a novel approach to prevent P. aeruginosa infections and as tools to detect HSLs in bodily fluids as a possible first clue to an undiagnosed Gram-negative infection. Using sheep immunization and recombinant antibody technology, a panel of sheep-mouse chimeric MAbs were generated which recognized HSL compounds with high sensitivity (nanomolar range) and cross-reactivity. These MAbs retained their nanomolar sensitivity in complex matrices and were able to recognize HSLs in P. aeruginosa cultures grown in the presence of urine. In a nematode slow-killing assay, HSL MAbs significantly increased the survival of worms fed on the antibiotic-resistant strain PA058. The therapeutic benefit of these MAbs was further studied using a mouse model of Pseudomonas infection in which groups of mice treated with HSL-2 and HSL-4 MAbs survived, 7 days after pathogen challenge, in significantly greater numbers (83 and 67%, respectively) compared with the control groups. This body of work has provided early proof-of-concept data to demonstrate the potential of HSL-specific, monoclonal antibodies as theranostic clinical leads suitable for the diagnosis, prevention, and treatment of life-threatening bacterial infections. PMID:24185854

  2. Heterogeneity of biofilms formed by nonmucoid Pseudomonas aeruginosa isolates from patients with cystic fibrosis

    DEFF Research Database (Denmark)

    Lee, Baoleri; Haagensen, Janus Anders Juul; Ciofu, O.;

    2005-01-01

    Biofilms are thought to play a key role in the occurrence of lung infections by Pseudomonas aeruginosa in patients with cystic fibrosis (CF). In this study, 20 nonmucoid P. aeruginosa isolates collected during different periods of chronic infection from eight CF patients were assessed with respect...

  3. In vivo activity of ceftobiprole in murine skin infections due to Staphylococcus aureus and Pseudomonas aeruginosa.

    Science.gov (United States)

    Fernandez, Jeffrey; Hilliard, Jamese J; Abbanat, Darren; Zhang, Wenyan; Melton, John L; Santoro, Colleen M; Flamm, Robert K; Bush, Karen

    2010-01-01

    Ceftobiprole, a broad-spectrum cephalosporin with activity against methicillin-resistant Staphylococcus aureus (MRSA) (P. Hebeisen et al., Antimicrob. Agents Chemother. 45:825-836, 2001), was evaluated in a subcutaneous skin infection model with Staphylococcus aureus Smith OC 4172 (methicillin-susceptible S. aureus [MSSA]), S. aureus OC 8525 (MRSA), Pseudomonas aeruginosa OC 4351 (having an inducible AmpC beta-lactamase), and P. aeruginosa OC 4354 (overproducing AmpC beta-lactamase). In the MSSA and MRSA infection models, ceftobiprole, administered as the prodrug ceftobiprole medocaril, was more effective in reducing CFU/g skin (P ceftobiprole were 19 to 29% lower than those for cefazolin-, vancomycin-, or linezolid-treated animals (P ceftobiprole-treated mice was 34% less than that with cefazolin or linezolid treatment (P ceftobiprole at similar doses was as effective as meropenem-cilastatin in reductions of CFU/g skin, despite 8- and 32-fold-lower MICs for meropenem; both treatments were more effective than was cefepime (P Ceftobiprole was similar to meropenem-cilastatin and 47 to 54% more effective than cefepime (P ceftobiprole is effective in reducing both bacterial load and lesion volume associated with infections due to MSSA, MRSA, and P. aeruginosa in this murine model of skin and soft tissue infection.

  4. Systemic Inflammatory Responses and Lung Injury following Hip Fracture Surgery Increases Susceptibility to Infection in Aged Rats

    Directory of Open Access Journals (Sweden)

    Hao Zhang

    2013-01-01

    Full Text Available Pulmonary infections frequently occur following hip fracture surgery in aged patients. However, the underlying reasons are not fully understood. The present study investigates the systemic inflammatory response and pulmonary conditions following hip fracture surgery as a means of identifying risk factors for lung infections using an aged rodent model. Aged, male Sprague-Dawley rats (8 animals per group underwent a sham procedure or hip fracture plus femoral intramedullary pinning. Animals were sacrificed 1, 3, and 7 days after the injury. Markers of systemic inflammation and pulmonary injury were analyzed. Both sham-operated and injured/surgical group animals underwent intratracheal inoculation with Pseudomonas aeruginosa 1, 3, and 7 days after surgery. P. aeruginosa counts in blood and bronchoalveolar lavage (BAL fluid and survival rates were recorded. Serum TNF-α, IL-6, IL-1β, and IL-10 levels and markers of pulmonary injury were significantly increased at 1 and 3 days following hip fracture and surgery. Animals challenged with P. aeruginosa at 1 and 3 days after injury had a significantly decreased survival rate and more P. aeruginosa recovered from blood and BAL fluid. This study shows that hip fracture and surgery in aged rats induced a systemic inflammatory response and lung injury associated with increased susceptibility to infection during the acute phase after injury and surgery.

  5. Study on antimicrobial potential of neem oil nanoemulsion against Pseudomonas aeruginosa infection in Labeo rohita.

    Science.gov (United States)

    Mishra, Prabhakar; R S, Suresh Kumar; Jerobin, Jayakumar; Thomas, John; Mukherjee, Amitava; Chandrasekaran, Natarajan

    2014-01-01

    Presence of several biochemical constituents in neem makes it an efficient antimicrobial agent for pathogenic diseases. The current investigation was aimed to assess the therapeutic potential of neem nanoemulsion as a control measure for Pseudomonas aeruginosa infection in freshwater fish Labeo rohita. The median lethal concentration (LC50) for the neem oil and neem nanoemulsion was 73.9 and 160.3 mg/L, respectively. The biomarker enzymes of treated fish tissues showed a significant difference in the level of glutathione reductase, catalase, and lipid peroxidation in neem oil-treated samples than in neem nanoemulsion-treated samples at Pneem nanoemulsion was more effective in both in vitro and in vivo methods. Present findings suggest that neem-based nanoemulsion has negligible toxicity to Rohu fishes. This makes neem-based nanoemulsion as an efficient therapeutic agent against P. aeruginosa infection, leading to its possible usage in the aquaculture industry.

  6. Les infections à Pseudomonas aeruginosa au service des maladies infectieuses du CHU YO, Burkina Faso: à propos deux cas

    Science.gov (United States)

    Mamoudou, Savadogo; Lassina, Dao; Fla, Koueta

    2015-01-01

    Nous rapportons deux cas d'infection à Pseudomonas aeruginosa: un cas de méningite et un cas d'infection urinaire. Les auteurs rappellent qu’à côté des étiologies classiques des méningites et des infections urinaires, des germes résistants comme Pseudomonas aeruginosa peuvent être responsables d'infections à localisation méningées et urinaires et dont il faut connaître pour une bonne prise en charge. Le traitement de ces infections requiert un antibiogramme au regard de la grande capacité de résistance de Pseudomonas aeruginosa en milieu hospitalier. La limitation des gestes invasifs et l'application rigoureuse des mesures de prévention des infections en milieu hospitalier contribueront à lutter efficacement contre ces infections en milieu de soins. PMID:26491521

  7. Pseudomonas aeruginosa tolerance to tobramycin, hydrogen peroxide and polymorphonuclear leukocytes is quorum-sensing dependent

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas; Jensen, Peter Østrup; Burmølle, Mette;

    2005-01-01

    The opportunistic human pathogen Pseudomonas aeruginosa is the predominant micro-organism of chronic lung infections in cystic fibrosis (CF) patients. P. aeruginosa colonizes the CF lungs by forming biofilm structures in the alveoli. In the biofilm mode of growth the bacteria are highly tolerant...

  8. Evaluation of Risk Factors for Antibiotic Resistance in Patients with Nosocomial Infections Caused by Pseudomonas aeruginosa

    Science.gov (United States)

    Ertem, Gunay; Erdinc, Fatma Sebnem; Kaya Kilic, Esra; Adiloglu, Ali; Hatipoglu, Cigdem

    2016-01-01

    Background. Pseudomonas aeruginosa (P. aeruginosa) is resistant to various antibiotics and can cause serious nosocomial infections with high morbidity and mortality. In this clinical study, we investigated the risk factors in patients who were diagnosed with P. aeruginosa-related nosocomial infection. Methods. A retrospective case control study including patients with P. aeruginosa-related nosocomial infection. Patients who were resistant to any of the six antibiotics (imipenem, meropenem, piperacillin-tazobactam, ciprofloxacin, amikacin, and ceftazidime) constituted the study group. Results. One hundred and twenty isolates were isolated. Various risk factors were detected for each antibiotic in the univariate analysis. In the multivariate analysis, previous cefazolin use was found as an independent risk factor for the development of imipenem resistance (OR = 3.33; CI 95% [1.11–10.0]; p = 0.03), whereas previous cerebrovascular attack (OR = 3.57; CI 95% [1.31–9.76]; p = 0.01) and previous meropenem use (OR = 4.13; CI 95% [1.21–14.07]; p = 0.02) were independent factors for the development of meropenem resistance. For the development of resistance to ciprofloxacin, hospitalization in the neurology intensive care unit (OR = 4.24; CI 95% [1.5–11.98]; p = 0.006) and mechanical ventilator application (OR = 11.7; CI 95% [2.24–61.45]; p = 0.004) were independent risk factors. Conclusion. The meticulous application of contact measures can decrease the rate of nosocomial infections. PMID:27656220

  9. Comparison of the systemic inflammatory response syndrome between monomicrobial and polymicrobial Pseudomonas aeruginosa nosocomial bloodstream infections

    Directory of Open Access Journals (Sweden)

    Wenzel Richard P

    2005-10-01

    Full Text Available Abstract Background Some studies of nosocomial bloodstream infection (nBSI have demonstrated a higher mortality for polymicrobial bacteremia when compared to monomicrobial nBSI. The purpose of this study was to compare differences in systemic inflammatory response and mortality between monomicrobial and polymicrobial nBSI with Pseudomonas aeruginosa. Methods We performed a historical cohort study on 98 adults with P. aeruginosa (Pa nBSI. SIRS scores were determined 2 days prior to the first positive blood culture through 14 days afterwards. Monomicrobial (n = 77 and polymicrobial BSIs (n = 21 were compared. Results 78.6% of BSIs were caused by monomicrobial P. aeruginosa infection (MPa and 21.4% by polymicrobial P. aeruginosa infection (PPa. Median APACHE II score on the day of BSI was 22 for MPa and 23 for PPa BSIs. Septic shock occurred in 33.3% of PPa and in 39.0% of MPa (p = 0.64. Progression to septic shock was associated with death more frequently in PPa (OR 38.5, CI95 2.9–508.5 than MPa (OR 4.5, CI95 1.7–12.1. Maximal SIR (severe sepsis, septic shock or death was seen on day 0 for PPa BSI vs. day 1 for MPa. No significant difference was noted in the incidence of organ failure, 7-day or overall mortality between the two groups. Univariate analysis revealed that APACHE II score ≥20 at BSI onset, Charlson weighted comorbidity index ≥3, burn injury and respiratory, cardiovascular, renal and hematologic failure were associated with death, while age, malignant disease, diabetes mellitus, hepatic failure, gastrointestinal complications, inappropriate antimicrobial therapy, infection with imipenem resistant P. aeruginosa and polymicrobial nBSI were not. Multivariate analysis revealed that hematologic failure (p Conclusion In this historical cohort study of nBSI with P. aeruginosa, the incidence of septic shock and organ failure was high in both groups. Additionally, patients with PPa BSI were not more acutely ill, as judged by APACHE II

  10. Annexin A2 Regulates Autophagy in Pseudomonas aeruginosa Infection through the Akt1-mTOR-ULK1/2 Signaling Pathway.

    Science.gov (United States)

    Li, Rongpeng; Tan, Shirui; Yu, Min; Jundt, Michael C; Zhang, Shuang; Wu, Min

    2015-10-15

    Earlier studies reported that a cell membrane protein, Annexin A2 (AnxA2), plays multiple roles in the development, invasion, and metastasis of cancer. Recent studies demonstrated that AnxA2 also functions in immunity against infection, but the underlying mechanism remains largely elusive. Using a mouse infection model, we reveal a crucial role for AnxA2 in host defense against Pseudomonas aeruginosa, as anxa2(-/-) mice manifested severe lung injury, systemic dissemination, and increased mortality compared with wild-type littermates. In addition, anxa2(-/-) mice exhibited elevated inflammatory cytokines (TNF-α, IL-6, IL-1β, and IFN-γ), decreased bacterial clearance by macrophages, and increased superoxide release in the lung. We further identified an unexpected molecular interaction between AnxA2 and Fam13A, which activated Rho GTPase. P. aeruginosa infection induced autophagosome formation by inhibiting Akt1 and mTOR. Our results indicate that AnxA2 regulates autophagy, thereby contributing to host immunity against bacteria through the Akt1-mTOR-ULK1/2 signaling pathway.

  11. Lung cancer in HIV-infected patients

    Directory of Open Access Journals (Sweden)

    R Palacios

    2012-11-01

    Full Text Available Purpose: Several studies have shown that HIV patients are at higher risk of lung cancer. Our aim is to analyse the prevalence and features of lung cancer in HIV-infected patients. Methods: The clinical charts of 4,721 HIV-infected patients seen in three hospitals of southeast Spain (study period 1992–2012 were reviewed, and all patients with a lung cancer were analysed. Results: There were 61 lung cancers, giving a prevalence of 1.2%. There was a predominance of men (82.0%, and smokers (96.6%; mean pack-years 35.2, with a median age of 48.0 (41.7–52.9 years, and their distribution according to risk group for HIV was: intravenous drug use 58.3%, homosexual 20.0%, and heterosexual 16.7%. Thirty-four (56.7% patients were Aids cases, and 29 (47.5% had prior pulmonar events: tuberculosis 16, bacterial pneumonia 9, and P. jiroveci pneumonia 4. The median nadir CD4 count was 149/mm3 (42–232, the median CD4 count at the time of diagnosis of the lung cancer was 237/mm3 (85–397, and 66.1%<350/mm3. 66.7% were on ART, and 70% of them had undetectable HIV viral load. The most common histological types of lung cancer were adenocarcinoma and epidermoid, with 24 (40.0% and 23 (38.3% cases, respectively. There were 49 (80.3% cases with advanced stages (III and IV at diagnosis. The distribution of treatments was: only palliative 23 (39.7%, chemotherapy 14 (24.1%, surgery and chemotherapy 8 (13.8%, radiotherapy 7 (12.1%, surgery 4 (6.9%, and other combined treatments 2 (3.4%. Forty-six (76.7% patients died, with a median survival time of 3 months. The Kaplan-Meier survival rate at 6 months was 42.7% (at 12 months 28.5%. Conclusions: The prevalence of lung cancer in this cohort of HIV-patients is high. People affected are mainly men, smokers, with transmission of HIV by intravenous drug use, and around half of them with prior opportunistic pulmonary events. Most patients had low nadir CD4 count, and were immunosuppressed at the time of diagnosis

  12. Immunogenic efficacy of differently produced recombinant vaccines candidates against Pseudomonas aeruginosa infections

    Institute of Scientific and Technical Information of China (English)

    1998-01-01

    Objective: To describe the expression and immunogenic efficacy of differently produced recombinant vaccines candidates against Pseudomonas aeruginosa infections. Methods: The hybrid protein OprF (aa 190-342)-Opr I (aa 21-83) was modified N-terminally, either with a minimal histidine tag or with a homologous sequence of OprF. Both recombinant proteins were purified by nickel chelate affinity chromatography under native and denaturing conditions. Results :This produced three suitable candidates for a vaccination trial: protein His-F- I , which was purified in its native as well as in its refolded form,and the native purified N-terminally extended protein ex-F- I . In mice, significantly higher antibody titers and survival rates after challenge with P. aeruginosa were observed, following immunization with protein His-F- I purified under native conditions. Conclusion: A hybrid OprF-Opr I molecule was cloned and a purification method which yields a protective vaccine against P. aeruginosa infections was established.

  13. Pseudomonas infection and mucociliary and absorptive clearance in the cystic fibrosis lung.

    Science.gov (United States)

    Locke, Landon W; Myerburg, Michael M; Weiner, Daniel J; Markovetz, Matthew R; Parker, Robert S; Muthukrishnan, Ashok; Weber, Lawrence; Czachowski, Michael R; Lacy, Ryan T; Pilewski, Joseph M; Corcoran, Timothy E

    2016-05-01

    Airway surface liquid hyperabsorption and mucus accumulation are key elements of cystic fibrosis lung disease that can be assessed in vivo using functional imaging methods. In this study we evaluated experimental factors affecting measurements of mucociliary clearance (MCC) and small-molecule absorption (ABS) and patient factors associated with abnormal absorption and mucus clearance.Our imaging technique utilises two radiopharmaceutical probes delivered by inhalation. Measurement repeatability was assessed in 10 adult cystic fibrosis subjects. Experimental factors were assessed in 29 adult and paediatric cystic fibrosis subjects (51 scans). Patient factors were assessed in a subgroup with optimal aerosol deposition (37 scans; 24 subjects). Paediatric subjects (n=9) underwent initial and 2-year follow-up scans. Control subjects from a previously reported study are included for comparison.High rates of central aerosol deposition influenced measurements of ABS and, to a lesser extent, MCC. Depressed MCC in cystic fibrosis was only detectable in subjects with previous Pseudomonas aeruginosa infection. Cystic fibrosis subjects without P. aeruginosa had similar MCC to control subjects. Cystic fibrosis subjects had consistently higher ABS rates.We conclude that the primary experimental factor affecting MCC/ABS measurements is central deposition percentage. Depressed MCC in cystic fibrosis is associated with P. aeruginosa infection. ABS is consistently increased in cystic fibrosis.

  14. Prevalence of Pseudomonas aeruginosa and Acinetobacter spp. in subgingival biofilm and saliva of subjects with chronic periodontal infection

    Directory of Open Access Journals (Sweden)

    Renata Souto

    2014-06-01

    Full Text Available P. aeruginosa and Acinetobacter spp. are important pathogens associated with late nosocomial pneumonia in hospitalized and institutionalized individuals. The oral cavity may be a major source of these respiratory pathogens, particularly in the presence of poor oral hygiene and periodontal infection. This study investigated the prevalence of P. aeruginosa and Acinetobacter spp. in subgingival biofilm and saliva of subjects with periodontal disease or health. Samples were obtained from 55 periodontally healthy (PH and 169 chronic periodontitis (CP patients. DNA was obtained from the samples and detection of P. aeruginosa and Acinetobacter spp. was carried out by multiplex and nested PCR. P. aeruginosa and Acinetobacter spp. were detected in 40% and 45% of all samples, respectively. No significant differences in the distribution of these microorganisms between men and women, subgingival biofilm and saliva samples, patients 35 years of age, and smokers and non-smokers were observed regardless periodontal status (p > 0.05. In contrast, the frequencies of P. aeruginosa and Acinetobacter spp. in saliva and biofilm samples were significantly greater in CP than PH patients (p < 0.01. Smokers presenting P. aeruginosa and high frequencies of supragingival plaque were more likely to present CP than PH. P. aeruginosa and Acinetobacter spp. are frequently detected in the oral microbiota of CP. Poor oral hygiene, smoking and the presence of P. aeruginosa are strongly associated with periodontitis.

  15. Mobile genetic elements of Pseudomonas aeruginosa isolates from hydrotherapy facility and respiratory infections.

    Science.gov (United States)

    Pereira, S G; Cardoso, O

    2014-03-01

    The content of mobile genetic elements in Pseudomonas aeruginosa isolates of a pristine natural mineral water system associated with healthcare was compared with clinical isolates from respiratory infections. One isolate, from the therapy pool circuit, presented a class 1 integron, with 100% similarity to a class 1 integron contained in plasmid p4800 of the Klebsiella pneumoniae Kp4800 strain, which is the first time it has been reported in P. aeruginosa. Class 1 integrons were found in 25.6% of the clinical isolates. PAGI1 orf3 was more prevalent in environmental isolates, while PAGI2 c105 and PAGI3 sg100 were more prevalent in clinical isolates. Plasmids were not observed in either population.

  16. Systems Biology Investigations of Pseudomonas aeruginosa Evolution in Association with Human Airway Infections

    DEFF Research Database (Denmark)

    Pedersen, Søren Damkiær

    Most knowledge about evolutionary adaptation has been gained from experimental evolution studies, in which organisms have been allowed to evolve under simple, well-defined conditions in the laboratory. While these studies have provided novel insight into the fundamental processes of evolutionary...... environments. The model system used for these investigations has been long-term chronic airway infections in Cystic fibrosis (CF) patients caused by the opportunistic pathogen Pseudomonas aeruginosa. Using a systems biology approach, we have monitored the adaptive development of the clinically important P....... aeruginosa DK2 clone lineage during 200,000 generations of evolution in the CF airways from its entrance in the clinic in the 1970’ies until the end of 2010. Genetic analysis showed that the DK2 lineage between 1973 and 2007 accumulated mutations in a near-linear manner with an overall genomic signature...

  17. Evaluation of Mannosidase and Trypsin Enzymes Effects on Biofilm Production of Pseudomonas aeruginosa Isolated from Burn Wound Infections

    Science.gov (United States)

    Banar, Maryam; Emaneini, Mohammad; Satarzadeh, Mhboubeh; Abdellahi, Nafiseh; Beigverdi, Reza; van Leeuwen, Willem B.; Jabalameli, Fereshteh

    2016-01-01

    Biofilm is an important virulence factor in Pseudomonas aeruginosa and has a substantial role in antibiotic resistance and chronic burn wound infections. New therapeutic agents against P. aeruginosa, degrading biofilms in burn wounds and improving the efficacy of current antimicrobial agents, are required. In this study, the effects of α-mannosidase, β-mannosidase and trypsin enzymes on the degradation of P. aeruginosa biofilms and on the reduction of ceftazidime minimum biofilm eliminating concentrations (MBEC) were evaluated. All tested enzymes, destroyed the biofilms and reduced the ceftazidime MBECs. However, only trypsin had no cytotoxic effect on A-431 human epidermoid carcinoma cell lines. In conclusion, since trypsin had better features than mannosidase enzymes, it can be a promising agent in combatting P. aeruginosa burn wound infections. PMID:27736961

  18. Impact of Pseudomonas aeruginosa quorum sensing on biofilm persistence in an in vivo intraperitoneal foreign-body infection model

    DEFF Research Database (Denmark)

    Christensen, Louise D; Moser, Claus; Jensen, Peter Ø

    2007-01-01

    Pseudomonas aeruginosa is an opportunistic human pathogen that causes chronic biofilm-based infections in host organisms. P. aeruginosa employs quorum sensing (QS) to control expression of its virulence, and to establish and maintain chronic infections. Under such conditions, the biofilm mode....... aeruginosa are cleared more rapidly from silicone implants as compared to their wild-type counterparts. Concurrently, treatment with the QS inhibitor furanone C-30 of mice harbouring implants colonized with the wild-type P. aeruginosa resulted in a significantly faster clearing of the implants as compared...... to the placebo-treated group. These results were obtained with both an inbred (BALB/c) and an outbred (NMRI) mouse strain. The present results support a model by which functional QS systems play a pivotal role in the ability of bacteria to resist clearing by the innate immune system and strongly suggest...

  19. Experimental Protection of Diabetic Mice against Lethal P. aeruginosa Infection by Bacteriophage

    Directory of Open Access Journals (Sweden)

    Nagaveni Shivshetty

    2014-01-01

    Full Text Available The emergence of antibiotic-resistant bacterial strains has become a global crisis and is vulnerable for the exploration of alternative antibacterial therapies. The present study emphasizes the use of bacteriophage for the treatment of multidrug resistant P. aeruginosa. P. aeruginosa was used to induce septicemia in streptozotocin (STZ induced diabetic and nondiabetic mice by intraperitoneal (i.p. injection of 3 × 108 CFU, resulting in a fatal bacteremia within 48 hrs. A single i.p. injection of 3 × 109 PFU phage GNCP showed efficient protection in both diabetic (90% and nondiabetic (100% bacteremic mice. It was further noted that the protection rate was reduced in diabetic mice when phage GNCP was administered after 4 h and 6 h of lethal bacterial challenge. In contrast, nondiabetic bacteremic mice were rescued even when treatment was delayed up to 20 h after lethal bacterial challenge. Evaluation of results confirmed that a single intraperitoneal injection of the phage dose (3 × 109 PFU/mL was more effective than the multiple doses of imipenem. These results uphold the efficacy of phage therapy against pernicious P. aeruginosa infections, especially in cases of immunocompromised host.

  20. Polysaccharides serve as scaffold of biofilms formed by mucoid Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Yang, Liang; Hengzhuang, Wang; Wu, Hong

    2012-01-01

    Chronic lung infection by mucoid Pseudomonas aeruginosa is one of the major pathologic features in patients with cystic fibrosis. Mucoid P. aeruginosa is notorious for its biofilm forming capability and resistance to immune attacks. In this study, the roles of extracellular polymeric substances...... from biofilms formed by mucoid P. aeruginosa were investigated. Alginate is not an essential structure component for mucoid P. aeruginosa biofilms. Genetic studies revealed that Pel and Psl polysaccharides serve as essential scaffold and mediate macrocolony formation in mucoid P. aeruginosa biofilms...

  1. Effect of ozone water rinse on wound healing in rats withPseudomonas aeruginosa infection

    Institute of Scientific and Technical Information of China (English)

    Ju-Hua Ye; Jun-Wu Huang; Hong-Yun Shi

    2016-01-01

    Objective:To study the promoting effect of ozone water rinse on wound healing in rats with Pseudomonas aeruginosa infection.Methods:Wistar male rats were selected as experimental animals and randomly divided into control group, chlorhexidine group and ozone water group,Pseudomonas aeruginosa-infected wounds were made and cleaned with normal saline, chlorhexidine and ozone water respectively; would healing of three groups was observed, wound tissue was collected and contents of inflammatory factors, apoptosis molecules and autophagy markers were detected.Results:Wound healing rates of chlorhexidine group and ozone water group were higher than that of control group and wound healing time was shorter than that of control group, wound healing rate of ozone water group was higher than that of chlorhexidine group and wound healing time was shorter than that of chlorhexidine group; TNF-α, IL-1, IL-2, Fas, FasL and Beclin-1 contents and LC3Ⅱ/LC3Ⅰ ratios in wound tissue of chlorhexidine group and ozone water group were lower than those of control group, and TNF-α, IL-1, IL-2, Fas, FasL and Beclin-1 contents and LC3Ⅱ/LC3Ⅰ ratios in wound tissue of ozone water group were lower than those of chlorhexidine group.Conclusions:Compared with normal saline and chlorhexidine, ozone water rinse helps to promote wound healing, improve wound healing rate and shorten wound healing time in rats withPseudomonas aeruginosa infection, and meanwhile it can inhibit cell apoptosis and autophagy in the wounds.

  2. Characterization of corneal damage from Pseudomonas aeruginosa infection by the use of multiphoton microscopy

    Science.gov (United States)

    Chang, Yu-Lin; Chen, Wei-Liang; Lo, Wen; Chen, Shean-Jen; Tan, Hsin-Yuan; Dong, Chen-Yuan

    2010-11-01

    Using multiphoton autofluorescence (MAF) and second harmonic generation (SHG) microscopy, we investigate the morphology and the structure of the corneal epithelium and stroma collagen of bovine cornea following injection of Pseudomonas aeruginosa. We found that corneal epithelial cells are damaged and stromal collagen becoming increasingly autofluorescent with time. We also characterized infected cornea cultured for 0, 6, 12, and 24 h by quantitative ratiometric MAF to SHG index (MAFSI) analysis. MAFSI results show that the destruction of the stromal collagen corresponds to a decrease in SHG intensity and increase of MAF signal with time.

  3. Outbreak of severe Pseudomonas aeruginosa infections caused by a contaminated drain in a whirlpool bathtub.

    Science.gov (United States)

    Berrouane, Y F; McNutt, L A; Buschelman, B J; Rhomberg, P R; Sanford, M D; Hollis, R J; Pfaller, M A; Herwaldt, L A

    2000-12-01

    During a 14-month period, 7 patients with hematological malignancies acquired serious infections caused by a single strain of multiply resistant Pseudomonas aeruginosa. A case-control study, culture surveys, and pulsed-field gel electrophoresis implicated a whirlpool bathtub on the unit as the reservoir. All case patients and 32% of control patients used this bathtub (P=.003). The epidemic strain was found only in cultures of samples taken from the bathtub. The drain of the whirlpool bathtub, which was contaminated with the epidemic strain, closed approximately 2.54 cm below the drain's strainer. Water from the faucet, which was not contaminated, became contaminated with P. aeruginosa from the drain when the tub was filled. The design of the drain allowed the epidemic strain to be transmitted to immunocompromised patients who used the whirlpool bathtub. Such tubs are used in many hospitals, and they may be an unrecognized source of nosocomial infections. This potential source of infection could be eliminated by using whirlpool bathtubs with drains that seal at the top.

  4. Pseudomonas aeruginosa biofilms in cystic fibrosis

    DEFF Research Database (Denmark)

    Høiby, Niels; Ciofu, Oana; Bjarnsholt, Thomas

    2010-01-01

    The persistence of chronic Pseudomonas aeruginosa lung infections in cystic fibrosis (CF) patients is due to biofilm-growing mucoid (alginate-producing) strains. A biofilm is a structured consortium of bacteria, embedded in a self-produced polymer matrix consisting of polysaccharide, protein...... and DNA. In CF lungs, the polysaccharide alginate is the major part of the P. aeruginosa biofilm matrix. Bacterial biofilms cause chronic infections because they show increased tolerance to antibiotics and resist phagocytosis, as well as other components of the innate and the adaptive immune system....... As a consequence, a pronounced antibody response develops, leading to immune complex-mediated chronic inflammation, dominated by polymorphonuclear leukocytes. The chronic inflammation is the major cause of the lung tissue damage in CF. Biofilm growth in CF lungs is associated with an increased frequency...

  5. Complement activation by Pseudomonas aeruginosa biofilms

    DEFF Research Database (Denmark)

    Jensen, E T; Kharazmi, A; Garred, P

    1993-01-01

    In chronic infections, such as the bronchopulmonary Pseudomonas aeruginosa infection in cystic fibrosis (CF) patients, bacteria persist despite an intact host immune defense and frequent antibiotic treatment. An important reason for the persistence of the bacteria is their capacity for the biofilm...... immuno-electrophoresis, C5a generation tested by a PMN chemotactic assay, and terminal complement complex formation measured by ELISA. Two of the four assays showed that P. aeruginosa grown in biofilm activated complement less than planktonic bacteria, and all assays showed that activation by intact...... influx of neutrophils are known to cause inflammatory changes in the lungs. P. aeruginosa persisting in biofilms may contribute to the constant inflammation taking place in the lungs of CF patients....

  6. Effect of bacteriophage infection in combination with tobramycin on the emergence of resistance in Escherichia coli and Pseudomonas aeruginosa biofilms.

    Science.gov (United States)

    Coulter, Lindsey B; McLean, Robert J C; Rohde, Rodney E; Aron, Gary M

    2014-10-03

    Bacteriophage infection and antibiotics used individually to reduce biofilm mass often result in the emergence of significant levels of phage and antibiotic resistant cells. In contrast, combination therapy in Escherichia coli biofilms employing T4 phage and tobramycin resulted in greater than 99% and 39% reduction in antibiotic and phage resistant cells, respectively. In P. aeruginosa biofilms, combination therapy resulted in a 60% and 99% reduction in antibiotic and PB-1 phage resistant cells, respectively. Although the combined treatment resulted in greater reduction of E. coli CFUs compared to the use of antibiotic alone, infection of P. aeruginosa biofilms with PB-1 in the presence of tobramycin was only as effective in the reduction of CFUs as the use of antibiotic alone. The study demonstrated phage infection in combination with tobramycin can significantly reduce the emergence of antibiotic and phage resistant cells in both E. coli and P. aeruginosa biofilms, however, a reduction in biomass was dependent on the phage-host system.

  7. Profile of Virulence Factors in the Multi-Drug Resistant Pseudomonas aeruginosa Strains of Human Urinary Tract Infections (UTI)

    Science.gov (United States)

    Habibi, Asghar; Honarmand, Ramin

    2015-01-01

    Background: Putative virulence factors are responsible for the pathogenicity of UTIs caused by Pseudomonas aeruginosa (P. aeruginosa). Resistance of P. aeruginosa to commonly used antibiotics is caused by the extreme overprescription of those antibiotics. Objectives: The goal of the present study was to investigate the prevalence of virulence factors and the antibiotic resistance patterns of P. aeruginosa isolates in UTI cases in Iran. Patients and Methods: Two hundred and fifty urine samples were collected from patients who suffered from UTIs. Samples were cultured immediately, and those that were P. aeruginosa-positive were analyzed for the presence of virulence genes using polymerase chain reaction (PCR) testing. Antimicrobial susceptibility testing (AST) was performed using the disk diffusion method. Results: Of the 250 urine samples analyzed, 8 samples (3.2%) were positive for P. aeruginosa. The prevalence of P. aeruginosa in male and female patients was 2.7% and 3.5%, respectively, (P = 0.035). In patients less than 10 years old, it was 4.2%, and in patients more than 55 years old, it was 4.2%. These were the most commonly infected groups. The highest levels of resistance were seen against ampicillin (87.5%), norfloxacin (62.5%), gentamycin (62.5%), amikacin (62.5%), and aztreonam (62.5%), while the lowest were seen for meropenem (0%), imipenem (12.5%), and polymyxin B (12.5%). LasB (87.5%), pclH (75%), pilB (75%), and exoS (75%) were the most commonly detected virulence factors in the P. aeruginosa isolates. Conclusions: It is logical to first prescribe meropenem, imipenem, and polymyxin B in cases of UTIs caused by P. aeruginosa. Medical practitioners should be aware of the presence of levels of antibiotic resistance in hospitalized UTI patients in Iran. PMID:26756017

  8. Glycerol metabolism promotes biofilm formation by Pseudomonas aeruginosa.

    Science.gov (United States)

    Scoffield, Jessica; Silo-Suh, Laura

    2016-08-01

    Pseudomonas aeruginosa causes persistent infections in the airways of cystic fibrosis (CF) patients. Airway sputum contains various host-derived nutrients that can be utilized by P. aeruginosa, including phosphotidylcholine, a major component of host cell membranes. Phosphotidylcholine can be degraded by P. aeruginosa to glycerol and fatty acids to increase the availability of glycerol in the CF lung. In this study, we explored the role that glycerol metabolism plays in biofilm formation by P. aeruginosa. We report that glycerol metabolism promotes biofilm formation by both a chronic CF isolate (FRD1) and a wound isolate (PAO1) of P. aeruginosa. Moreover, loss of the GlpR regulator, which represses the expression of genes involved in glycerol metabolism, enhances biofilm formation in FRD1 through the upregulation of Pel polysaccharide. Taken together, our results suggest that glycerol metabolism may be a key factor that contributes to P. aeruginosa persistence by promoting biofilm formation.

  9. Draft Genome Sequence of Extremely Drug-Resistant Pseudomonas aeruginosa (ST357) Strain CMC_VB_PA_B22862 Isolated from a Community-Acquired Bloodstream Infection

    Science.gov (United States)

    Pragasam, Agila Kumari; Yesurajan, Francis; Doss C, George Priya; George, Biju; Devanga Ragupathi, Naveen Kumar; Walia, Kamini

    2016-01-01

    Extremely drug-resistant Pseudomonas aeruginosa strains causing severe infections have become a serious concern across the world. Here, we report draft genome sequence of P. aeruginosa with an extremely drug-resistant profile isolated from a patient with community-acquired bloodstream infection in India.

  10. Increased serum concentration of G-CSF in cystic fibrosis patients with chronic Pseudomonas aeruginosa pneumonia

    DEFF Research Database (Denmark)

    Jensen, P Ø; Moser, C; Kharazmi, A;

    2006-01-01

    Chronic Pseudomonas aeruginosa lung infection is the major reason for premature death in patients with cystic fibrosis (CF). Infected patients experience a progressive deterioration of the lung tissue caused by a persistent accumulation of PMNs. We investigated if the pulmonary accumulation of PMNs...

  11. Typing of Pseudomonas aeruginosa strains in Norwegian cystic fibrosis patients

    DEFF Research Database (Denmark)

    Fluge, G; Ojeniyi, B; Høiby, N;

    2001-01-01

    OBJECTIVES: Typing of Pseudomonas aeruginosa isolates from Norwegian cystic fibrosis (CF) patients with chronic Pseudomonas lung infection in order to see whether cross-infection might have occurred. METHODS: Isolates from 60 patients were collected during the years 1994-98, and typed by pulsed...

  12. Preventing Pseudomonas aeruginosa and Chromobacterium violaceum infections by anti-adhesion-active components of edible seeds

    Directory of Open Access Journals (Sweden)

    Rachmaninov Ofra

    2012-02-01

    Full Text Available Abstract Background Pseudomonas aeruginosa adhesion to animal/human cells for infection establishment involves adhesive proteins, including its galactose- and fucose-binding lectins PA-IL (LecA and PA-IIL (LecB. The lectin binding to the target-cell receptors may be blocked by compatible glycans that compete with those of the receptors, functioning as anti-adhesion glycodecoys. The anti-adhesion treatment is of the utmost importance for abrogating devastating antibiotic-resistant P. aeruginosa infections in immunodeficient and cystic fibrosis (CF patients. This strategy functions in nature in protecting embryos and neonates. We have shown that PA-IL, PA-IIL, and also CV-IIL (a PA-IIL homolog produced in the related pathogen Chromobacterium violaceum are highly useful for revealing natural glycodecoys that surround embryos in diverse avian eggs and are supplied to neonates in milks and royal jelly. In the present study, these lectins were used as probes to search for seed embryo-protecting glycodecoys. Methods The lectin-blocking glycodecoy activities were shown by the hemagglutination-inhibition test. Lectin-binding glycoproteins were detected by Western blotting with peroxidase-labeled lectins. Results The present work reports the finding - by using PA-IL, PA-IIL, and CV-IIL - of rich glycodecoy activities of low ( 10 kDa compounds (including glycoproteins in extracts of cashew, cocoa, coffee, pumpkin, and tomato seeds, resembling those of avian egg whites, mammal milks, and royal jelly. Conclusions Edible seed extracts possess lectin-blocking glycodecoys that might protect their embryos from infections and also might be useful for hampering human and animal infections.

  13. Prevalence of Pseudomonas aeruginosa and Acinetobacter spp. in subgingival biofilm and saliva of subjects with chronic periodontal infection.

    Science.gov (United States)

    Souto, Renata; Silva-Boghossian, Carina M; Colombo, Ana Paula Vieira

    2014-01-01

    P. aeruginosa and Acinetobacter spp. are important pathogens associated with late nosocomial pneumonia in hospitalized and institutionalized individuals. The oral cavity may be a major source of these respiratory pathogens, particularly in the presence of poor oral hygiene and periodontal infection. This study investigated the prevalence of P. aeruginosa and Acinetobacter spp. in subgingival biofilm and saliva of subjects with periodontal disease or health. Samples were obtained from 55 periodontally healthy (PH) and 169 chronic periodontitis (CP) patients. DNA was obtained from the samples and detection of P. aeruginosa and Acinetobacter spp. was carried out by multiplex and nested PCR. P. aeruginosa and Acinetobacter spp. were detected in 40% and 45% of all samples, respectively. No significant differences in the distribution of these microorganisms between men and women, subgingival biofilm and saliva samples, patients ≤ 35 and > 35 years of age, and smokers and non-smokers were observed regardless periodontal status (p > 0.05). In contrast, the frequencies of P. aeruginosa and Acinetobacter spp. in saliva and biofilm samples were significantly greater in CP than PH patients (p Acinetobacter spp. are frequently detected in the oral microbiota of CP. Poor oral hygiene, smoking and the presence of P. aeruginosa are strongly associated with periodontitis.

  14. Pseudomonas aeruginosa suppresses interferon response to rhinovirus infection in cystic fibrosis but not in normal bronchial epithelial cells.

    Science.gov (United States)

    Chattoraj, Sangbrita S; Ganesan, Shyamala; Faris, Andrea; Comstock, Adam; Lee, Wai-Ming; Sajjan, Umadevi S

    2011-10-01

    Despite increased morbidity associated with secondary respiratory viral infections in cystic fibrosis (CF) patients with chronic Pseudomonas aeruginosa infection, the underlying mechanisms are not well understood. Here, we investigated the effect of P. aeruginosa infection on the innate immune responses of bronchial epithelial cells to rhinovirus (RV) infection. CF cells sequentially infected with mucoid P. aeruginosa (MPA) and RV showed lower levels of interferons (IFNs) and higher viral loads than those of RV-infected cells. Unlike results for CF cells, normal bronchial epithelial cells coinfected with MPA/RV showed higher IFN expression than RV-infected cells. In both CF and normal cells, the RV-stimulated IFN response requires phosphorylation of Akt and interferon response factor 3 (IRF3). Preinfection with MPA inhibited RV-stimulated Akt phosphorylation and decreased IRF3 phosphorylation in CF cells but not in normal cells. Compared to normal, unstimulated CF cells or normal cells treated with CFTR inhibitor showed increased reactive oxygen species (ROS) production. Treatment of CF cells with antioxidants prior to MPA infection partially reversed the suppressive effect of MPA on the RV-stimulated IFN response. Together, these results suggest that MPA preinfection inhibits viral clearance by suppressing the antiviral response particularly in CF cells but not in normal cells. Further, increased oxidative stress in CF cells appears to modulate the innate immune responses to coinfection.

  15. Multidrug resistant Psudomonas aeruginosa infections complicating surgical wounds and the potential challenges in managing post-operative wound infections:University of Calabar Teaching Hospital experience

    Institute of Scientific and Technical Information of China (English)

    Jombo GT; Akpan S; Epoke J; Denen Akaa P; Odey F

    2010-01-01

    Objective:To ascertain the antimicrobial susceptibility profile of Pseudomonas aeruginosa (P. aeruginosa) recovered from surgical site infections (SSIs). Methods:The study was retrospective in nature and was compiled for a period of five years (1st February, 2004-31st January, 2009). Data were generated from the culture of post-operative wound swab specimens by the microbiology laboratory of University of Calabar Teaching Hospital. Relevant information from the patients’ records was compiled, such as age, gender, type of surgical procedure, microorganisms recovered and their antibiotic sensitivity patterns. Obtained data was analysed by using Epi Info 6 statistical software. Results:Of the 4 533 wound swab specimens processed, 673 were culture positive and P. aeruginosa was recovered from 13.1%of the culture positive specimens with its rate of recovery decreasing with age progression (P0.05). Most of the P. aeruginosa isolates were from general surgery wards and least from orthopaedic wards. Ofloxacin, ceftriaxone and augmentin were the most active antibiotics while ampicillin, tetracycline and co-trimoxazole were the least active antibiotics, with no antibiotic having a 100%activity against the organism. Conclusions:In view of the high resistance displayed by P. aeruginosa recovered from SSIs, adequate antiseptic procedures should be entrenched to avoid colonization of surgical wounds by this microorganism as well as others with similar sensitivity profile. Ofloxacin, ceftriaxone and augmentin may be considered for prevention of P.aeruginosa infection.

  16. Effects of phosphate supplementation on Pseudomonas aeruginosa invasive behavior in burn wound infections: A simple approach to a big problem.

    Science.gov (United States)

    Mohammadi-Samani, Soliman; Kouroshfard, Shahriyar; Azarpira, Negar

    2016-03-01

    This study was designed to investigate the effect of inorganic phosphate supplementation on invasive behavior of Pseudomonas aeruginosa in burn wound infections. An emulsion-based lotion containing sodium dihydrogen phosphate was formulated and then 50 female Sprague-Dawley rats with burn wounds were used to assess the effect of phosphate supplementation on swarming motility of P. aeruginosa. On the second day after burn, four groups of rats were inoculated with P. aeruginosa and one group was left as negative control. The treatment was started on day 3 and the animals were followed up for 4 weeks. Significant improvement in wound healing was observed in the phosphate-receiving group after the 4-week follow-up, compared to the negative control, positive control, and silver sulfadiazine-receiving groups. Histopathological assessment of the tissue samples also indicated the healing process in phosphate-enriched lotion receiving group. The results showed that inorganic phosphate supplementation results in alteration of the virulence behavior of P. aeruginosa and improvement in the wound healing process. In conclusion, phosphate supplementation would be a rational strategy in the eradication of P. aeruginosa wound infection.

  17. Aloe vera Gel: Effective Therapeutic Agent against Multidrug-Resistant Pseudomonas aeruginosa Isolates Recovered from Burn Wound Infections

    Directory of Open Access Journals (Sweden)

    Mehdi Goudarzi

    2015-01-01

    Full Text Available Objective. Aloe vera is an herbal medicinal plant with biological activities, such as antimicrobial, anticancer, anti-inflammatory, and antidiabetic ones, and immunomodulatory properties. The purpose of this study was investigation of in vitro antimicrobial activity of A. vera gel against multidrug-resistant (MDR Pseudomonas aeruginosa isolated from patients with burn wound infections. Methods. During a 6-month study, 140 clinical isolates of P. aeruginosa were collected from patients admitted to the burn wards of a hospital in Tehran, Iran. Antimicrobial susceptibility test was carried out against the pathogens using the A. vera gel and antibiotics (imipenem, gentamicin, and ciprofloxacin. Results. The antibiogram revealed that 47 (33.6% of all isolates were MDR P. aeruginosa. The extract isolated from A. vera has antibacterial activity against all of isolates. Also, 42 (89.4% isolates were inhibited by A. vera gel extract at minimum inhibitory concentration (MIC ≤ 200 µg/mL. MIC value of A. vera gel for other isolates (10.6% was 800 µg/mL. All of MDR P. aeruginosa strains were inhibited by A. vera at similar MIC50 and MIC90 200 µg/mL. Conclusion. Based on our results, A. vera gel at various concentrations can be used as an effective antibacterial agent in order to prevent wound infection caused by P. aeruginosa.

  18. Aloe vera Gel: Effective Therapeutic Agent against Multidrug-Resistant Pseudomonas aeruginosa Isolates Recovered from Burn Wound Infections.

    Science.gov (United States)

    Goudarzi, Mehdi; Fazeli, Maryam; Azad, Mehdi; Seyedjavadi, Sima Sadat; Mousavi, Reza

    2015-01-01

    Objective. Aloe vera is an herbal medicinal plant with biological activities, such as antimicrobial, anticancer, anti-inflammatory, and antidiabetic ones, and immunomodulatory properties. The purpose of this study was investigation of in vitro antimicrobial activity of A. vera gel against multidrug-resistant (MDR) Pseudomonas aeruginosa isolated from patients with burn wound infections. Methods. During a 6-month study, 140 clinical isolates of P. aeruginosa were collected from patients admitted to the burn wards of a hospital in Tehran, Iran. Antimicrobial susceptibility test was carried out against the pathogens using the A. vera gel and antibiotics (imipenem, gentamicin, and ciprofloxacin). Results. The antibiogram revealed that 47 (33.6%) of all isolates were MDR P. aeruginosa. The extract isolated from A. vera has antibacterial activity against all of isolates. Also, 42 (89.4%) isolates were inhibited by A. vera gel extract at minimum inhibitory concentration (MIC) ≤ 200 µg/mL. MIC value of A. vera gel for other isolates (10.6%) was 800 µg/mL. All of MDR P. aeruginosa strains were inhibited by A. vera at similar MIC50 and MIC90 200 µg/mL. Conclusion. Based on our results, A. vera gel at various concentrations can be used as an effective antibacterial agent in order to prevent wound infection caused by P. aeruginosa.

  19. Impact of Pseudomonas aeruginosa quorum sensing on biofilm persistence in an in vivo intraperitoneal foreign-body infection model

    DEFF Research Database (Denmark)

    Christensen, Louise Dahl; Moser, Claus; Jensen, Peter Ø;

    2007-01-01

    of growth contributes significantly to P. aeruginosa tolerance to the action of the innate and adaptive defence system and numerous antibiotics. In the present study, an in vivo foreign-body infection model was established in the peritoneal cavity of mice. Experimental data showed that QS-deficient P...

  20. Large-area burns with pandrug-resistant Pseudomonas aeruginosa infection and respiratory failure

    Institute of Scientific and Technical Information of China (English)

    NING Fang-gang; ZHAO Xiao-zhuo; BIAN Jing; ZHANG Guo-an

    2011-01-01

    Background Infection due to pandrug-resistant Pseudomonas aeruginosa (PDRPA) has become a challenge in clinical practice. The aim of this research was to summarize the treatment of large-area burns (60%-80%) with PDRPA infection and respiratory failure in our hospital over the last two years, and to explore a feasible treatment protocol for such patients.Methods We retrospectively analyzed the treatment of five patients with large-area burns accompanied by PDRPA infection and respiratory failure transferred to our hospital from burn units in hospitals in other Chinese cities from January 2008 to February 2010. Before PDRPA infection occurred, all five patients had open wounds with large areas of granulation because of the failure of surgery and dissolving of scar tissue; they had also undergone long-term administration of carbapenems. This therapy included ventilatory support, rigorous repair of wounds, and combined antibiotic therapy targeted at drug-resistance mechanisms, including carbapenems, ciprofloxacin, macrolide antibiotics and β-lactamase inhibitors.Results Four patients recovered from bums and one died after therapy.Conclusions First, compromised immunity caused by delayed healing of burn wounds in patients with large-area bums and long-term administration of carbapenems may be the important factors in the initiation and progression of PDRPA infection. Second, if targeted at drug-resistance mechanisms, combined antibiotic therapy using carbapenems,ciprofloxacin, macrolide antibiotics and β-lactamase inhibitors could effectively control PDRPA infection. Third, although patients with large-area burns suffered respiratory failure and had high risks from anesthesia and surgery, only aggressive skin grafting with ventilatory support could control the infection and save lives. Patients may not be able to tolerate a long surgical procedure, so the duration of surgery should be minimized, and the frequency of surgery increased.

  1. Selection of phages and conditions for the safe phage therapy against Pseudomonas aeruginosa infections

    Institute of Scientific and Technical Information of China (English)

    Victor; Krylov; Olga; Shaburova; Elena; Pleteneva; Sergey; Krylov; Alla; Kaplan; Maria; Burkaltseva; Olga; Polygach; Elena; Chesnokova

    2015-01-01

    The emergence of multidrug-resistant bacterial pathogens forced us to consider the phage therapy as one of the possible alternative approaches to treatment. The purpose of this paper is to consider the conditions for the safe, long-term use of phage therapy against various infections caused by Pseudomonas aeruginosa. We describe the selection of the most suitable phages, their most effective combinations and some approaches for the rapid recognition of phages unsuitable for use in therapy. The benefi ts and disadvantages of the various different approaches to the preparation of phage mixtures are considered, together with the specifi c conditions that are required for the safe application of phage therapy in general hospitals and the possibilities for the development of personalized phage therapy.

  2. Selection of phages and conditions for the safe phage therapy against Pseudomonas aeruginosa infections.

    Science.gov (United States)

    Krylov, Victor; Shaburova, Olga; Pleteneva, Elena; Krylov, Sergey; Kaplan, Alla; Burkaltseva, Maria; Polygach, Olga; Chesnokova, Elena

    2015-02-01

    The emergence of multidrug-resistant bacterial pathogens forced us to consider the phage therapy as one of the possible alternative approaches to treatment. The purpose of this paper is to consider the conditions for the safe, long-term use of phage therapy against various infections caused by Pseudomonas aeruginosa. We describe the selection of the most suitable phages, their most effective combinations and some approaches for the rapid recognition of phages unsuitable for use in therapy. The benefits and disadvantages of the various different approaches to the preparation of phage mixtures are considered, together with the specific conditions that are required for the safe application of phage therapy in general hospitals and the possibilities for the development of personalized phage therapy.

  3. Nosocomial urinary tract infection in the intensive care unit: when should Pseudomonas aeruginosa be suspected? Experience of the French national surveillance of nosocomial infections in the intensive care unit, Rea-Raisin.

    Science.gov (United States)

    Venier, A-G; Lavigne, T; Jarno, P; L'heriteau, F; Coignard, B; Savey, A; Rogues, A-M

    2012-01-01

    Individual and ward risk factors for P. aeruginosa-induced urinary tract infection in the case of nosocomial urinary tract infection in the intensive care unit were determined with hierarchical (multilevel) logistic regression. The 2004-2006 prospective French national intensive care unit nosocomial infection surveillance dataset was used and 3252 patients with urinary tract infection were included; 16% were infected by P. aeruginosa. Individual risk factors were male sex, duration of stay, antibiotics at admission and transfer from another intensive care unit. Ward risk factors were patient turnover and incidence of P. aeruginosa-infected patients.

  4. Cyanophage infection in the bloom-forming cyanobacteria Microcystis aeruginosa in surface freshwater.

    Science.gov (United States)

    Yoshida-Takashima, Yukari; Yoshida, Mitsuhiro; Ogata, Hiroyuki; Nagasaki, Keizo; Hiroishi, Shingo; Yoshida, Takashi

    2012-01-01

    Host-like genes are often found in viral genomes. To date, multiple host-like genes involved in photosynthesis and the pentose phosphate pathway have been found in phages of marine cyanobacteria Synechococcus and Prochlorococcus. These gene products are predicted to redirect host metabolism to deoxynucleotide biosynthesis for phage replication while maintaining photosynthesis. A cyanophage, Ma-LMM01, infecting the toxic cyanobacterium Microcystis aeruginosa, was isolated from a eutrophic freshwater lake and assigned as a member of a new lineage of the Myoviridae family. The genome encodes a host-like NblA. Cyanobacterial NblA is known to be involved in the degradation of the major light harvesting complex, the phycobilisomes. Ma-LMM01 nblA gene showed an early expression pattern and was highly transcribed during phage infection. We speculate that the co-option of nblA into Microcystis phages provides a significant fitness advantage to phages by preventing photoinhibition during infection and possibly represents an important part of the co-evolutionary interactions between cyanobacteria and their phages.

  5. A peptide of heparin cofactor II inhibits endotoxin-mediated shock and invasive Pseudomonas aeruginosa infection.

    Directory of Open Access Journals (Sweden)

    Martina Kalle

    Full Text Available Sepsis and septic shock remain important medical problems with high mortality rates. Today's treatment is based mainly on using antibiotics to target the bacteria, without addressing the systemic inflammatory response, which is a major contributor to mortality in sepsis. Therefore, novel treatment options are urgently needed to counteract these complex sepsis pathologies. Heparin cofactor II (HCII has recently been shown to be protective against Gram-negative infections. The antimicrobial effects were mapped to helices A and D of the molecule. Here we show that KYE28, a 28 amino acid long peptide representing helix D of HCII, is antimicrobial against the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, the Gram-positive Bacillus subtilis and Staphylococcus aureus, as well as the fungus Candida albicans. Moreover, KYE28 binds to LPS and thereby reduces LPS-induced pro-inflammatory responses by decreasing NF-κB/AP-1 activation in vitro. In mouse models of LPS-induced shock, KYE28 significantly enhanced survival by dampening the pro-inflammatory cytokine response. Finally, in an invasive Pseudomonas infection model, the peptide inhibited bacterial growth and reduced the pro-inflammatory response, which lead to a significant reduction of mortality. In summary, the peptide KYE28, by simultaneously targeting bacteria and LPS-induced pro-inflammatory responses represents a novel therapeutic candidate for invasive infections.

  6. Baicalein attenuates the quorum sensing-controlled virulence factors of Pseudomonas aeruginosa and relieves the inflammatory response in P. aeruginosa-infected macrophages by downregulating the MAPK and NFκB signal-transduction pathways

    Directory of Open Access Journals (Sweden)

    Luo J

    2016-01-01

    Full Text Available Jing Luo,* Jin-liang Kong,* Bi-ying Dong, Hong Huang, Ke Wang, Li-hong Wu, Chang-chun Hou, Yue Liang, Bing Li, Yi-qiang Chen Department of Respiratory Disease, First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China *These authors contributed equally to this work Abstract: Burgeoning antibiotic resistance and unfavorable outcomes of inflammatory injury after Pseudomonas aeruginosa infection have necessitated the development of novel agents that not only target quorum sensing (QS but also combat inflammatory injury with the least risk of resistance. This study aimed to assess the anti-QS and anti-inflammatory activities of baicalein, a traditional herbal medicine that is widely used in the People’s Republic of China, against P. aeruginosa infection. We found that subminimum inhibitory concentrations of baicalein efficiently interfered with the QS-signaling pathway of P. aeruginosa via downregulation of the transcription of QS-regulated genes and the translation of QS-signaling molecules. This interference resulted in the global attenuation of QS-controlled virulence factors, such as motility and biofilm formation, and the secretion into the culture supernatant of extracellular virulence factors, including pyocyanin, LasA protease, LasB elastase, and rhamnolipids. Moreover, we examined the anti-inflammatory activity of baicalein and its mode of action via a P. aeruginosa-infected macrophage model to address its therapeutic effect. Baicalein reduced the P. aeruginosa-induced secretion of the inflammatory cytokines IL-1β, IL-6, IL-8, and TNFα. In addition, baicalein suppressed P. aeruginosa-induced activation of the MAPK and NFκB signal-transduction pathways in cocultured macrophages; this may be the mechanism by which baicalein inhibits the production of proinflammatory cytokines. Therefore, our study demonstrates that baicalein represents a potential treatment for P. aeruginosa infection because it

  7. Insights into the respiratory tract microbiota of patients with cystic fibrosis during early Pseudomonas aeruginosa colonization

    Energy Technology Data Exchange (ETDEWEB)

    Keravec, Marlene; Mounier, Jerome; Prestat , Emmanuel; Vallet, Sophie; Jansson, Janet K.; Bergaud , Gaetaqn; Rosec, Silvain; Gourious, Stephanie; Rault, Gilles; Coton, Emmanuel; Barbier, George; Hery-Arnaud, Geneveieve

    2015-08-09

    Abstract Pseudomonas aeruginosa plays a major role in cystic fibrosis (CF) progression. Therefore, it is important to understand the initial steps of P. aeruginosa infection. The structure and dynamics of CF respiratory tract microbial communities during the early stages of P. aeruginosa colonization were characterized by pyrosequencing and cloning-sequencing. The respiratory microbiota showed high diversity, related to the young age of the CF cohort (mean age 10 years). Wide inter- and intra-individual variations were revealed. A common core microbiota of 5 phyla and 13 predominant genera was found, the majority of which were obligate anaerobes. A few genera were significantly more prevalent in patients never infected by P. aeruginosa. Persistence of an anaerobic core microbiota regardless of P. aeruginosa status suggests a major role of certain anaerobes in the pathophysiology of lung infections in CF. Some genera may be potential biomarkers of pulmonary infection state.

  8. Development of Liposomal Ciprofloxacin to Treat Lung Infections

    Directory of Open Access Journals (Sweden)

    David Cipolla

    2016-03-01

    Full Text Available Except for management of Pseudomonas aeruginosa (PA in cystic fibrosis, there are no approved inhaled antibiotic treatments for any other diseases or for infections from other pathogenic microorganisms such as tuberculosis, non-tuberculous mycobacteria, fungal infections or potential inhaled biowarfare agents including Francisella tularensis, Yersinia pestis and Coxiella burnetii (which cause pneumonic tularemia, plague and Q fever, respectively. Delivery of an antibiotic formulation via the inhalation route has the potential to provide high concentrations at the site of infection with reduced systemic exposure to limit side effects. A liposomal formulation may improve tolerability, increase compliance by reducing the dosing frequency, and enhance penetration of biofilms and treatment of intracellular infections. Two liposomal ciprofloxacin formulations (Lipoquin® and Pulmaquin® that are in development by Aradigm Corporation are described here.

  9. Rapid Necrotic Killing of Polymorphonuclear Leukocytes Is Caused by Quorum-Sensing-Controlled Production of Rhamnolipid by Pseudomonas Aeruginosa

    DEFF Research Database (Denmark)

    Jensen, P. Ø.; Bjarnsholt, Thomas; Phipps, Richard Kerry

    2007-01-01

    a QS-regulated tolerance of biofilm bacteria to the antimicrobial properties of polymorphonuclear leukocytes (PMNs). The precise QS-regulated effect on the PMNs is, however, unknown. Incubation of human PMNs with supernatants from dense P. aeruginosa cultures showed that the QS-competent P. aeruginosa...... induced rapid necrosis of the PMNs. This mechanism was also observed in mouse lungs infected with P. aeruginosa, and in sputum obtained from P.-aeruginosa-infected patients with cystic fibrosis. Evidence is presented that the necrotic effect was caused by rhamnolipids, production of which is QS controlled...

  10. Antibiotic Resistance Pattern of Pseudomonas Aeruginosa, Isolated from Patient with Burn Wound Infection in Guilan,Iran

    Directory of Open Access Journals (Sweden)

    Iraj Nikokar

    2013-03-01

    Full Text Available Background and Objectives: Antibiotic resistance of Pseudomonas aeruginosa remains a major problem in burn patients. The main objective of this study was to determine the antibiotic resistance pattern and frequency of class 1 integrons among P. aeruginosa strains isolated from patients with burn wound infections in a new Burn Centre in Guilan, Iran.Materials and Methods: The bacterial isolates were collected from 182 patients with burn wound infections and P. aeruginosa species were identified by standard bacteriological methods. The drug susceptibility test, using 11 antimicrobial agents, was performed for all the isolates via agar disk diffusion method. PCR was carried out for the detection of integrons.Results: Out of a total of 182 hospitalized patients in the burn center assessed, 86 (47% found to have P. aeruginosa in their isolates. Resistance rates to various antibiotics were as follows: cloxacillin (91.8%, cotrimoxazole (86%, cephazolin (83.7%, carbenicillin (74.4%, piperacillin (69.9%, ceftazidime (68.8%, ciprofloxacin (66.3%, tobramycin (58.2%, amikacin (48.8% and gentamicin (37.2%, while the most effective antibiotic was imipenem with a resistance rate of 23.3%. Thirty nine (45.3% isolates were detected as multi-drug resistant. The PCR results showed that 37 (43% P. aeruginosa isolates and 27 (69.2% multi-drug resistant strains harbored class 1 integrons. A significant correlation was obtained between the presence of integrons and resistance against imipenem, ceftazidime, piperacillin and ciprofloxacin (P < 0.001.Conclusion: Optimization of using antimicrobial agents and control of infection is recommended to prevent the increasing population of drug resistant organisms in the new burn centre setting in this study. Furthermore, the high frequency of class 1 integrons among multi-drug resistant strains might be responsible for dissemination of antibiotic resistance gene.

  11. Pseudomonas aeruginosa Infection in a Group of Captive Humboldt Penguins ( Spheniscus humboldti ).

    Science.gov (United States)

    Widmer, Dimitri; Ziemssen, Eva; Schade, Benjamin; Kappe, Eva; Schmitt, Ferdinand; Kempf, Hermann; Wibbelt, Gudrun

    2016-06-01

    Nine Humboldt penguins ( Spheniscus humboldti ), between 1 and 1.5 years old and kept at Zoo Dresden, developed local and systemic infections with various opportunistic pathogens within a period of 4 months. Affected birds died peracutely without preceding symptoms or showed various clinical signs, including separation from conspecifics, reduced food intake, lethargy, dyspnea, swelling of the salt glands, and ocular discharge. One bird showed central nervous signs, including seizures. Pathologic examination of deceased birds revealed severe necrotizing inflammation of the mucous membranes and deep structures of the glottis, trachea, nasal sinus, and conchae and granulomatous inflammation of the salt glands. Further findings were airsacculitis, pneumonia, hepatitis, conjunctivitis, and myositis. Pseudomonas aeruginosa was the predominant pathogen in 7 cases. Six penguins died or were euthanatized, whereas 3 penguins that received systemic antibiotic treatment with tobramycin (10 mg/kg IM q24h for 10 days) showed rapid clinical improvement. Insufficient turnover rate of the filtration system, biofilm formation on pipe surfaces, and other factors are assumed to have promoted pathogen buildup in the pool water and subsequent infection.

  12. Coexistence and Within-Host Evolution of Diversified Lineages of Hypermutable Pseudomonas aeruginosa in Long-term Cystic Fibrosis Infections

    DEFF Research Database (Denmark)

    Feliziani, Sofia; Marvig, Rasmus Lykke; Lujan, Adela M.;

    2014-01-01

    The advent of high-throughput sequencing techniques has made it possible to follow the genomic evolution of pathogenic bacteria by comparing longitudinally collected bacteria sampled from human hosts. Such studies in the context of chronic airway infections by Pseudomonas aeruginosa in cystic...... to investigate within-host population diversity or long-term evolution of mutators in CF airways. We sequenced the genomes of 13 and 14 isolates of P. aeruginosa mutator populations from an Argentinian and a Danish CF patient, respectively. Our collection of isolates spanned 6 and 20 years of patient infection...... of the patient. Analysis of the mutations identified genes that underwent convergent evolution across lineages and sub-lineages, suggesting that the genes were targeted by mutation to optimize pathogenic fitness. Parallel evolution was observed in reduction of overall catabolic capacity of the populations...

  13. Prevalence and risk factors associated with colonization and infection of extensively drug-resistant Pseudomonas aeruginosa: a systematic review.

    Science.gov (United States)

    Buhl, Michael; Peter, Silke; Willmann, Matthias

    2015-01-01

    Pseudomonas aeruginosa is a Gram-negative human pathogen with extensively drug-resistant (XDR) strains emerging in hospitals across the globe. This systematic review is focused on the worldwide prevalence of XDR P. aeruginosa (XDR-PA) and on the risk factors associated with its colonization and infection, based on literature available through PubMed, Web of Science and BioMed Central databases. An overview of surveillance systems is provided as well as a synopsis on the prevalence of XDR-PA, showing an increase in recent reports. Risk factors independently associated with XDR-PA colonization or infections are described in four groups with reference to antimicrobial therapy, medical devices as well as patient- and hospital environment-related factors.

  14. Relationship between Ceftolozane-Tazobactam Exposure and Selection for Pseudomonas aeruginosa Resistance in a Hollow-Fiber Infection Model

    OpenAIRE

    VanScoy, Brian D.; Mendes, Rodrigo E.; Castanheira, Mariana; McCauley, Jennifer; Bhavnani, Sujata M.; Jones, Ronald N.; Friedrich, Lawrence V.; Steenbergen, Judith N.; Ambrose, Paul G.

    2014-01-01

    It is important to understand the relationship between antibiotic exposure and the selection of drug resistance in the context of therapy exposure. We sought to identify the ceftolozane-tazobactam exposure necessary to prevent the amplification of drug-resistant bacterial subpopulations in a hollow-fiber infection model. Two Pseudomonas aeruginosa challenge isolates were selected for study, a wild-type ATCC strain (ceftolozane-tazobactam MIC, 0.5 mg/liter) and a clinical isolate (ceftolozane-...

  15. Investigation of the presence of human or bovine respiratory syncytial virus in the lungs of mink (Neovison vison) with hemorrhagic pneumonia due to Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Salomonsen, Charlotte Mark; Breum, Solvej Østergaard; Larsen, Lars Erik;

    2012-01-01

    Background Hemorrhagic pneumonia is a disease of farmed mink (Neovison vison) caused by Pseudomonas aeruginosa. The disease is highly seasonal in Danish mink with outbreaks occurring almost exclusively in the autumn. Human respiratory syncytial virus (RSV) has been shown to augment infection with...

  16. Necrotizing Lung Infection Caused by the Protozoan Balantidium coli

    Directory of Open Access Journals (Sweden)

    Sat Sharma

    2003-01-01

    Full Text Available Balantidium coli, a ciliated protozoan, is well known to cause intestinal infection in humans. Extraintestinal spread to the peritoneal cavity and genitourinary tract has rarely been reported. There have also been a few cases of lung involvement from this parasite. A case of B coli causing a thick-walled right upper lobe cavity in an organic farmer who had contact with aerosolized pig manure is reported. Bronchoalveolar lavage fluid examined for ova and parasite revealed trophozoites of B coli in large numbers. Treatment with doxycycline hyclate led to marked improvement. Necrotizing lung infection caused by the protozoan B coli should be considered in individuals who report contact with pigs.

  17. Paragonimus kellicotti: A Lung Infection in Our Own Backyard

    Directory of Open Access Journals (Sweden)

    Eric Johannesen

    2016-01-01

    Full Text Available Paragonimiasis is an infection caused by the lung fluke of the genus Paragonimus. Within the United States, paragonimiasis has been commonly diagnosed in Southeast Asian immigrants infected with the Asian lung fluke Paragonimus westermani. Infections from the North American lung fluke, Paragonimus kellicotti, have been rare, although more infections have been seen in people in the Midwestern United States. A 29-year-old male with a history of pleomorphic xanthoastrocytoma presented with hemoptysis. A CT scan showed a mass in the left upper lung lobe. A biopsy showed eosinophils and parasite eggs, some with a recognizable operculum. Further investigation revealed that he takes canoe trips on rivers within Missouri and would eat crayfish caught from these rivers. A blood sample was confirmed positive for Paragonimiasis serologically at the Center for Disease Control. Paragonimus kellicotti is found in rivers within the Mississippi basin. Infection occurs by consuming uncooked or undercooked crawfish. Microscopic identification of parasite eggs has been the gold standard. Serologic tests have been developed to aid in the diagnosis. Patients typically present with fever and hemoptysis. Common CT findings include pleural effusion, a mass, and lymphadenopathy. Awareness of P. kellicotti is important to guide appropriate diagnostic testing and ensuring proper treatment.

  18. Paragonimus kellicotti: A Lung Infection in Our Own Backyard.

    Science.gov (United States)

    Johannesen, Eric; Nguyen, Van

    2016-01-01

    Paragonimiasis is an infection caused by the lung fluke of the genus Paragonimus. Within the United States, paragonimiasis has been commonly diagnosed in Southeast Asian immigrants infected with the Asian lung fluke Paragonimus westermani. Infections from the North American lung fluke, Paragonimus kellicotti, have been rare, although more infections have been seen in people in the Midwestern United States. A 29-year-old male with a history of pleomorphic xanthoastrocytoma presented with hemoptysis. A CT scan showed a mass in the left upper lung lobe. A biopsy showed eosinophils and parasite eggs, some with a recognizable operculum. Further investigation revealed that he takes canoe trips on rivers within Missouri and would eat crayfish caught from these rivers. A blood sample was confirmed positive for Paragonimiasis serologically at the Center for Disease Control. Paragonimus kellicotti is found in rivers within the Mississippi basin. Infection occurs by consuming uncooked or undercooked crawfish. Microscopic identification of parasite eggs has been the gold standard. Serologic tests have been developed to aid in the diagnosis. Patients typically present with fever and hemoptysis. Common CT findings include pleural effusion, a mass, and lymphadenopathy. Awareness of P. kellicotti is important to guide appropriate diagnostic testing and ensuring proper treatment.

  19. Pseudomonas aeruginosa infection in patients with cystic fibrosis: scientific evidence regarding clinical impact, diagnosis, and treatment

    Directory of Open Access Journals (Sweden)

    Luiz Vicente Ribeiro Ferreira da Silva Filho

    2013-06-01

    Full Text Available Evidence-based techniques have been increasingly used in the creation of clinical guidelines and the development of recommendations for medical practice. The use of levels of evidence allows the reader to identify the quality of scientific information that supports the recommendations made by experts. The objective of this review was to address current concepts related to the clinical impact, diagnosis, and treatment of Pseudomonas aeruginosa infections in patients with cystic fibrosis. For the preparation of this review, the authors defined a group of questions that would be answered in accordance with the principles of PICO–an acronym based on questions regarding the Patients of interest, Intervention being studied, Comparison of the intervention, and Outcome of interest. For each question, a structured review of the literature was performed using the Medline database in order to identify the studies with the methodological design most appropriate to answering the question. The questions were designed so that each of the authors could write a response. A first draft was prepared and discussed by the group. Recommendations were then made on the basis of the level of scientific evidence, in accordance with the classification system devised by the Oxford Centre for Evidence-Based Medicine, as well as the level of agreement among the members of the group.

  20. Rapid development in vitro and in vivo of resistance to ceftazidime in biofilm-growing Pseudomonas aeruginosa due to chromosomal beta-lactamase

    DEFF Research Database (Denmark)

    Bagge, N; Ciofu, O; Skovgaard, L T;

    2000-01-01

    The aim of this study was to examine the development of resistance of biofilm-growing P. aeruginosa during treatment with ceftazidime. Biofilms were established in vitro using a modified Robbins device (MRD) and in vivo in the rat model of chronic lung infection. Three P. aeruginosa strains...

  1. Real-time PCR detection of host-mediated cyanophage gene transcripts during infection of a natural Microcystis aeruginosa population.

    Science.gov (United States)

    Yoshida, Mitsuhiro; Yoshida, Takashi; Yoshida-Takashima, Yukari; Kashima, Aki; Hiroishi, Shingo

    2010-01-01

    The aim of this study was to develop a quantitative real-time reverse transcription-PCR (real-time RT-PCR) assay to detect and quantify mRNA of cyanophages within infected Microcystis aeruginosa cells in a freshwater pond. Laboratory-based data showed that the relative abundance of the cyanophage g91 mRNA within host cells increased before cyanophage numbers increased in culture. This transcriptional pattern indicated the kinetics of the viral infection suggesting the real-time RT-PCR method to be a potential tool for environmental monitoring of cyanophage infections. In this field survey, the numbers of infected M. aeruginosa cell populations estimated from cyanophage numbers were low at 0.01-2.9 cells mL(-1). The highest relative abundance of phage g91 RNA (10(-2) per rnpB transcript) was at about the same levels of expression as laboratory-based growth data for Ma-LMM01 (estimated density of infected host cells: 10(5) cells mL(-1)); and was observed when cyanophage numbers rapidly increased (as well as a decrease in host cell numbers). Quantification of cyanophage numbers is important to understand ecological relationships between the phage and its hosts. Our data suggest the quantification of phage gene transcripts within a natural host cell population to be a strong tool for investigating the quantitative effects of phage lysis during infection of the host population.

  2. The TAK1→IKKβ→TPL2→MKK1/MKK2 signaling cascade regulates IL-33 expression in Cystic Fibrosis airway epithelial cells following infection by Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Raquel eFarias

    2016-01-01

    Full Text Available In cystic fibrosis (CF, chronic respiratory infections result in an exaggerated and uncontrolled inflammatory response that ultimately lead to a decrease in pulmonary function. We have previously described the presence of the alarmin IL-33 in lung explants from CF patients. The signals regulating IL-33 expression in the airway epithelium following a gram-negative bacterial infection are currently unknown. Our objective was to characterize the pathways in CF airway epithelial cells (AECs leading to an increase in IL-33 expression. We found that, in CF AECs expressing a deletion of a phenylalanine at position 508 of the gene coding for Cystic Fibrosis Transmembrane Conductance Regulator (CFTRdelF508, exposure to live Pseudomonas aeruginosa upregulates IL-33 via the TLR2 and TLR5 signalling pathways. This up-regulation can be partially or fully reverted by pre-incubating CFTRdelF508 AECs with a CFTR corrector (VX-809 and/or a CFTR potentiator (VX-770. Similarly, incubation with the CFTR corrector and/or the CFTR potentiator also decreased IL-8 expression in response to infection. Moreover, using different protein kinase inhibitors that target elements downstream of TLR signalling, we show that the TAK1→IKKβ→TPL2→MKK1/MKK2 pathway regulates IL-33 expression following an infection with P. aeruginosa. Our findings represent the first characterization of the signals regulating IL-33 expression in CF airway epithelial cells in response to a bacterial infection.

  3. Real-Time PCR Detection of Host-Mediated Cyanophage Gene Transcripts during Infection of a Natural Microcystis aeruginosa Population

    OpenAIRE

    Yoshida, Mitsuhiro; Yoshida, Takashi; Yoshida-Takashima, Yukari; Kashima, Aki; Hiroishi, Shingo

    2010-01-01

    The aim of this study was to develop a quantitative real-time reverse transcription-PCR (real-time RT-PCR) assay to detect and quantify mRNA of cyanophages within infected Microcystis aeruginosa cells in a freshwater pond. Laboratory-based data showed that the relative abundance of the cyanophage g91 mRNA within host cells increased before cyanophage numbers increased in culture. This transcriptional pattern indicated the kinetics of the viral infection suggesting the real-time RT-PCR method ...

  4. Sinus surgery postpones chronic Gram-negative lung infection

    DEFF Research Database (Denmark)

    Alanin, M C; Aanaes, K; Høiby, N

    2016-01-01

    of pulmonary samples positive for GNB. We investigated whether the effect is sustained. METHODOLOGY: We report the effect of ESS and adjuvant therapy three years postoperatively in a CF cohort participating in this prospective clinical follow-up study. The primary endpoint was the lung infection status defined...

  5. Multifocal Rhizopus microsporus lung infection following brush clearing

    Directory of Open Access Journals (Sweden)

    Artsiom V. Tsyrkunou

    2014-10-01

    Full Text Available We report a case of pulmonary Rhizopus microsporus infection in a patient with untreated diabetes following brush clearing. The patient was successfully treated with a combined medical and surgical approach with complete resolution of the lung lesions and remains asymptomatic at 11-month follow-up.

  6. Tasco®: A Product of Ascophyllum nodosum Enhances Immune Response of Caenorhabditis elegans Against Pseudomonas aeruginosa Infection

    Directory of Open Access Journals (Sweden)

    Franklin Evans

    2012-01-01

    Full Text Available The effects of Tasco®, a product made from the brown seaweed (Ascophyllum nodosum were tested for the ability to protect Caenorhabditis elegans against Pseudomonas aeruginosa infection. A water extract of Tasco® (TWE reduced P. aeruginosa inflicted mortality in the nematode. The TWE, at a concentration of 300 µg/mL, offered the maximum protection and induced the expression of innate immune response genes viz.; zk6.7 (Lypases, lys-1 (Lysozyme, spp-1 (Saponin like protein, f28d1.3 (Thaumatin like protein, t20g5.7 (Matridin SK domain protein, abf-1 (Antibacterial protein and f38a1.5 (Lectin family protein. Further, TWE treatment also affected a number of virulence components of the P. aeuroginosa and reduced its secreted virulence factors such as lipase, proteases and toxic metabolites; hydrogen cyanide and pyocyanin. Decreased virulence factors were associated with a significant reduction in expression of regulatory genes involved in quorum sensing, lasI, lasR, rhlI and rhlR. In conclusion, the TWE-treatment protected the C. elegans against P. aeruginosa infection by a combination of effects on the innate immunity of the worms and direct effects on the bacterial quorum sensing and virulence factors.

  7. Twenty-five-year outbreak of Pseudomonas aeruginosa infecting individuals with cystic fibrosis: identification of the prairie epidemic strain.

    Science.gov (United States)

    Parkins, Michael D; Glezerson, Bryan A; Sibley, Christopher D; Sibley, Kristen A; Duong, Jessica; Purighalla, Swathi; Mody, Christopher H; Workentine, Matthew L; Storey, Douglas G; Surette, Michael G; Rabin, Harvey R

    2014-04-01

    Transmissible strains of Pseudomonas aeruginosa have been described for cystic fibrosis (CF) and may be associated with a worse prognosis. Using a comprehensive strain biobank spanning 3 decades, we sought to determine the prevalence and stability of chronic P. aeruginosa infection in an adult population. P. aeruginosa isolates from sputum samples collected at initial enrollment in our adult clinic and at the most recent clinic visit were examined by a combination of pulsed-field gel electrophoresis and multilocus sequence typing and compared against a collection of established transmissible and local non-CF bronchiectasis (nCFB) isolates. A total of 372 isolates from 107 patients, spanning 674 patient-years, including 66 patients with matched isolates from initial and final encounters, were screened. A novel clone with increased antibacterial resistance, termed the prairie epidemic strain (PES), was found in 29% (31/107 patients) of chronically infected patients referred from multiple prairie-based CF centers. This isolate was not found in those diagnosed with CF as adults or in a control population with nCFB. While 90% (60/66 patients) of patients had stable infection over a mean of 10.8 years, five patients experienced strain displacement of unique isolates, with PES occurring within 2 years of transitioning to adult care. PES has been present in our cohort since at least 1987, is unique to CF, generally establishes chronic infection during childhood, and has been found in patients at the time of transition of patients from multiple prairie-based CF clinics, suggesting broad endemicity. Studies are under way to evaluate the clinical implications of PES infection.

  8. Outbreak of infection in a burns unit due to Pseudomonas aeruginosa originating from contaminated tubing used for irrigation of patients

    DEFF Research Database (Denmark)

    Kolmos, H J; Thuesen, B; Nielsen, S V;

    1993-01-01

    Five patients with extensive deep burns developed septicaemia due to Pseudomonas aeruginosa serogroup O-7.8 and phage type 21 or 21/188 shortly after they had been admitted to hospital. Four other burned patients became colonized with the same strain. The source of infection was contaminated tap...... water used for irrigation of the burns, as part of the first-aid treatment which the patients received when entering the hospital. Contamination was restricted to showers and tubing that were permanently connected to the taps, and the outbreak stopped after they had been disinfected. Tubing and showers...... used for irrigation of burns should be dismantled and heat-disinfected after each patient and not reconnected to the taps until immediately before the next treatment. Taps used for irrigation of burns should be monitored regularly for the presence of P. aeruginosa and other potentially pathogenic...

  9. INADEQUATE ANTIBODY-RESPONSE AGAINST RESPIRATORY VIRAL-INFECTION IN LONG-SURVIVING RAT LUNG ALLOGRAFTS

    NARCIS (Netherlands)

    WINTER, JB; GROEN, M; VANDERLOGT, K; WILDEVUUR, CRH; PROP, J

    1995-01-01

    Lung transplant recipients suffer from a high number of viral infections. It has been suggested that the defense against viral infections is impaired in lung transplants, Therefore, we investigated in rat lung transplants whether antibody responses against an intrapulmonary viral infection were impa

  10. The Role of Newly Discovered Exotoxin (S Toxin) in Pseudomonas aeruginosa Infections

    Science.gov (United States)

    1981-08-01

    Pseudomonas aeruginosa and Enterobacter aerogenes and bilirubin and SGOT of 280 units. On the third day after his initial procedure he was begun on...under halothane anesthesia. A blood culture drawn for a temperature of 104°F was reported as positive for Pseudomonas aeruginosa on the next day (Sth... growth media, culture methods and specific S antisera have all bee described in detail in previous annual reports., S antigen was quantitated by

  11. Characterization of Cytomegalovirus Lung Infection in Non-HIV Infected Children

    Directory of Open Access Journals (Sweden)

    Sonia M. Restrepo-Gualteros

    2014-05-01

    Full Text Available Cytomegalovirus (CMV is a prevalent pathogen in the immunocompromised host and invasive pneumonia is a feared complication of the virus in this population. In this pediatric case series we characterized CMV lung infection in 15 non-HIV infected children (median age 3 years; IQR 0.2–4.9 years, using current molecular and imaging diagnostic modalities, in combination with respiratory signs and symptoms. The most prominent clinical and laboratory findings included cough (100%, hypoxemia (100%, diffuse adventitious breath sounds (100% and increased respiratory effort (93%. All patients had abnormal lung images characterized by ground glass opacity/consolidation in 80% of cases. CMV was detected in the lung either by CMV PCR in bronchoalveolar lavage (82% detection rate or histology/immunohistochemistry in lung biopsy (100% detection rate. CMV caused respiratory failure in 47% of children infected and the overall mortality rate was 13.3%. Conclusion: CMV pneumonia is a potential lethal disease in non-HIV infected children that requires a high-index of suspicion. Common clinical and radiological patterns such as hypoxemia, diffuse adventitious lung sounds and ground-glass pulmonary opacities may allow early identification of CMV lung infection in the pediatric population, which may lead to prompt initiation of antiviral therapy and better clinical outcomes.

  12. Catheter-related infections caused by Pseudomonas aeruginosa: virulence factors involved and their relationships.

    Science.gov (United States)

    Olejnickova, Katerina; Hola, Veronika; Ruzicka, Filip

    2014-11-01

    The nosocomial pathogen Pseudomonas aeruginosa is equipped with a large arsenal of cell-associated and secreted virulence factors which enhance its invasive potential. The complex relationships among virulence determinants have hitherto not been fully elucidated. In the present study, 175 catheter-related isolates were observed for the presence of selected virulence factors, namely extracellular enzymes and siderophore production, biofilm formation, resistance to antibiotics, and motility. A high percentage of the strains produced most of the tested virulence factors. A positive correlation was identified between the production of several exoproducts, and also between the formation of both types of biofilm. An opposite trend was observed between the two types of biofilm and the production of siderophores. Whereas the relationship between the submerged biofilm production (i.e. the biofilm formed on the solid surface below the water level) and the siderophore secretion was negative, the production of air-liquid interface (A-L) biofilm (i.e. the biofilm floating on the surface of the cultivation medium) and the siderophore secretion were positively correlated. All correlations were statistically significant at the level P = 0.05 with the correlation coefficient γ ≥ 0.50. Our results suggest that: (1) the co-production of the lytic enzymes and siderophores can play an important role in the pathogenesis of the catheter-related infections and should be taken into account when the virulence potential is assessed; (2) biofilm-positive strains are capable of forming both submerged and non-attached A-L biofilms; and (3) the different micro-environment in the submerged biofilm and A-L biofilm layers have opposite consequences for the production of other virulence factors.

  13. Ma-LMM01 infecting toxic Microcystis aeruginosa illuminates diverse cyanophage genome strategies.

    Science.gov (United States)

    Yoshida, Takashi; Nagasaki, Keizo; Takashima, Yukari; Shirai, Yoko; Tomaru, Yuji; Takao, Yoshitake; Sakamoto, Shigetaka; Hiroishi, Shingo; Ogata, Hiroyuki

    2008-03-01

    Cyanobacteria and their phages are significant microbial components of the freshwater and marine environments. We identified a lytic phage, Ma-LMM01, infecting Microcystis aeruginosa, a cyanobacterium that forms toxic blooms on the surfaces of freshwater lakes. Here, we describe the first sequenced freshwater cyanomyovirus genome of Ma-LMM01. The linear, circularly permuted, and terminally redundant genome has 162,109 bp and contains 184 predicted protein-coding genes and two tRNA genes. The genome exhibits no colinearity with previously sequenced genomes of cyanomyoviruses or other Myoviridae. The majority of the predicted genes have no detectable homologues in the databases. These findings indicate that Ma-LMM01 is a member of a new lineage of the Myoviridae family. The genome lacks homologues for the photosynthetic genes that are prevalent in marine cyanophages. However, it has a homologue of nblA, which is essential for the degradation of the major cyanobacteria light-harvesting complex, the phycobilisomes. The genome codes for a site-specific recombinase and two prophage antirepressors, suggesting that it has the capacity to integrate into the host genome. Ma-LMM01 possesses six genes, including three coding for transposases, that are highly similar to homologues found in cyanobacteria, suggesting that recent gene transfers have occurred between Ma-LMM01 and its host. We propose that the Ma-LMM01 NblA homologue possibly reduces the absorption of excess light energy and confers benefits to the phage living in surface waters. This phage genome study suggests that light is central in the phage-cyanobacterium relationships where the viruses use diverse genetic strategies to control their host's photosynthesis.

  14. Isolation and characterization of a cyanophage infecting the toxic cyanobacterium Microcystis aeruginosa.

    Science.gov (United States)

    Yoshida, Takashi; Takashima, Yukari; Tomaru, Yuji; Shirai, Yoko; Takao, Yoshitake; Hiroishi, Shingo; Nagasaki, Keizo

    2006-02-01

    We isolated a cyanophage (Ma-LMM01) that specifically infects a toxic strain of the bloom-forming cyanobacterium Microcystis aeruginosa. Transmission electron microscopy showed that the virion is composed of anisometric head and a tail complex consisting of a central tube and a contractile sheath with helical symmetry. The morphological features and the host specificity suggest that Ma-LMM01 is a member of the cyanomyovirus group. Using semi-one-step growth experiments, the latent period and burst size were estimated to be 6 to 12 h and 50 to 120 infectious units per cell, respectively. The size of the phage genome was estimated to be ca. 160 kbp using pulse-field gel electrophoresis; the nucleic acid was sensitive to DNase I, Bal31, and all 14 restriction enzymes tested, suggesting that it is a linear double-stranded DNA having a low level of methylation. Phylogenetic analyses based on the deduced amino acid sequences of two open reading frames coding for ribonucleotide reductase alpha- and beta-subunits showed that Ma-LMM01 forms a sister group with marine and freshwater cyanobacteria and is apparently distinct from T4-like phages. Phylogenetic analysis of the deduced amino acid sequence of the putative sheath protein showed that Ma-LMM01 does not form a monophyletic group with either the T4-like phages or prophages, suggesting that Ma-LMM01 is distinct from other T4-like phages that have been described despite morphological similarity. The host-phage system which we studied is expected to contribute to our understanding of the ecology of Microcystis blooms and the genetics of cyanophages, and our results suggest the phages could be used to control toxic cyanobacterial blooms.

  15. ExoU activates NF-κB and increases IL-8/KC secretion during Pseudomonas aeruginosa infection.

    Directory of Open Access Journals (Sweden)

    Carolina Diettrich Mallet de Lima

    Full Text Available ExoU, a Pseudomonas aeruginosa cytotoxin injected into host cytosol by type III secretion system, exhibits a potent proinflammatory activity that leads to a marked recruitment of neutrophils to infected tissues. To evaluate the mechanisms that account for neutrophil infiltration, we investigated the effect of ExoU on IL-8 secretion and NF-κB activation. We demonstrate that ExoU increases IL-8 mRNA and protein levels in P. aeruginosa-infected epithelial and endothelial cell lines. Also, ExoU induces the nuclear translocation of p65/p50 NF-κB transactivator heterodimer as well as NF-κB-dependent transcriptional activity. ChIP assays clearly revealed that ExoU promotes p65 binding to NF-κB site in IL-8 promoter and the treatment of cultures with the NF-κB inhibitor Bay 11-7082 led to a significant reduction in IL-8 mRNA levels and protein secretion induced by ExoU. These results were corroborated in a murine model of pneumonia that revealed a significant reduction in KC secretion and neutrophil infiltration in bronchoalveolar lavage when mice were treated with Bay 11-7082 before infection with an ExoU-producing strain. In conclusion, our data demonstrate that ExoU activates NF-κB, stimulating IL-8 expression and secretion during P. aeruginosa infection, and unveils a new mechanism triggered by this important virulence factor to interfere in host signaling pathways.

  16. Bacterial sinusitis can be a focus for initial lung colonisation and chronic lung infection in patients with cystic fibrosis

    DEFF Research Database (Denmark)

    Aanæs, Kasper

    2013-01-01

    A major purpose of treating patients with cystic fibrosis (CF) is to prevent or delay chronic lung infections with CF-pathogenic Gram-negative bacteria. In the intermittent stage, bacteria can usually be eradicated from the lungs with antibiotics, but following eradication, the next lung colonisa...... therapy, e.g. saline and antibiotic irrigations....

  17. Magnetic resonance imaging of lung infections in children

    Energy Technology Data Exchange (ETDEWEB)

    Peltola, Ville; Ruuskanen, Olli [Turku University Hospital, Department of Paediatrics, Turku (Finland); Svedstroem, Erkki [Turku University Hospital, Department of Radiology, Turku (Finland)

    2008-11-15

    The advantages and limitations of MRI in lung infections in children have not been well established. This article illustrates the MRI findings in children with pneumonia caused by Mycoplasma pneumoniae, Streptococcus pneumoniae, and other pathogens. Lung parenchymal, pleural, and lymph node abnormalities are well characterized by MRI. Loculation of pleural fluid is detected in children with empyema. Contrast enhancement may be useful in the differentiation of active inflammation from noninflammatory changes. MRI can be particularly useful in the follow-up of children with chronic pulmonary diseases. (orig.)

  18. Efficacy of 1% acetic acid in the treatment of chronic wounds infected with Pseudomonas aeruginosa: prospective randomised controlled clinical trial.

    Science.gov (United States)

    Madhusudhan, V L

    2016-12-01

    Chronic wounds are those wounds that are persistent and do not respond to any sort of treatment. The concept of using topical antiseptics on open wounds is to prevent and treat infections. They also help to shorten the time taken to heal the wounds. The use of topical agents on wounds to prevent infection is a minimal ability to develop resistance to the microorganisms. Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen with innate resistance to many antibiotics. In places that are economically backward, these problems get compounded by the inability of patients to afford newer expensive drugs. Topically applied dilute acetic acid, which is cheap and easily available, has been found to be effective in such chronic wounds. In the present study, an attempt has been made to use 1% acetic acid as the sole antimicrobial agent for the treatment of pseudomonal wound infections. A control limb was used in which the wounds were treated with normal saline. Our objective was to evaluate the efficacy of acetic acid in low concentration of 1% in chronic wounds infected with P. aeruginosa. This was a prospective study conducted over a period of 6 months.

  19. Reactive-oxygen-species-mediated P. aeruginosa killing is functional in human cystic fibrosis macrophages.

    Directory of Open Access Journals (Sweden)

    Noemi Cifani

    Full Text Available Pseudomonas aeruginosa is the most common pathogen for chronic lung infection in cystic fibrosis (CF patients. About 80% of adult CF patients have chronic P. aeruginosa infection, which accounts for much of the morbidity and most of the mortality. Both bacterial genetic adaptations and defective innate immune responses contribute to the bacteria persistence. It is well accepted that CF transmembrane conductance regulator (CFTR dysfunction impairs the airways-epithelium-mediated lung defence; however, other innate immune cells also appear to be affected, such as neutrophils and macrophages, which thus contribute to this infectious pathology in the CF lung. In macrophages, the absence of CFTR has been linked to defective P. aeruginosa killing, increased pro-inflammatory cytokine secretion, and reduced reactive oxygen species (ROS production. To learn more about macrophage dysfunction in CF patients, we investigated the generation of the oxidative burst and its impact on bacterial killing in CF macrophages isolated from peripheral blood or lung parenchyma of CF patients, after P. aeruginosa infection. Our data demonstrate that CF macrophages show an oxidative response of similar intensity to that of non-CF macrophages. Intracellular ROS are recognized as one of the earliest microbicidal mechanisms against engulfed pathogens that are activated by macrophages. Accordingly, NADPH inhibition resulted in a significant increase in the intracellular bacteria survival in CF and non-CF macrophages, both as monocyte-derived macrophages and as lung macrophages. These data strongly suggest that the contribution of ROS to P. aeruginosa killing is not affected by CFTR mutations.

  20. Vaccination promotes TH1-like inflammation and survival in chronic Pseudomonas aeruginosa pneumonia. A new prophylactic principle

    DEFF Research Database (Denmark)

    Johansen, H K; Cryz, S J; Hougen, H P

    1997-01-01

    . In a rat model of acute P. aeruginosa pneumonia we studied whether it was possible to improve the initial bacterial clearance and diminish the inflammatory response by vaccination prior to challenge with free, live P. aeruginosa. The vaccines studied were PAO 579 sonicate, O-polysaccharide toxin A (TA...... of the macroscopic lung inflammation compared to the other vaccination groups (p = 0.009). The same effect could be obtained by IFN-gamma treatment (p = 0.004). The chronic P. aeruginosa lung infection was established in two inbred mice strains C3H/HeN, known as TH1 responders, and Balb/c, known as TH2 responders...

  1. A Galleria mellonella infection model reveals double and triple antibiotic combination therapies with enhanced efficacy versus a multidrug-resistant strain of Pseudomonas aeruginosa.

    Science.gov (United States)

    Krezdorn, Jessica; Adams, Sophie; Coote, Peter J

    2014-07-01

    The aim of this study was to compare the inhibitory effect of antibiotic combinations in vitro with efficacy in Galleria mellonella larvae in vivo to identify efficacious combinations that target Pseudomonas aeruginosa. P. aeruginosa NCTC 13437, a multidrug-resistant strain resistant to β-lactams and aminoglycosides, was used. Susceptibility to cefotaxime, piperacillin, meropenem, amikacin, levofloxacin and colistin alone, or in dual or triple combinations, was measured in vitro via a 24 h time-kill assay. In vitro results were then compared with the efficacy of the same dual or triple antibiotic combinations versus G. mellonella larvae infected with P. aeruginosa. G. mellonella haemolymph burden of P. aeruginosa was determined over 96 h post-infection and treatment with the most potent combination therapies. Many dual and triple combinations of antibiotics displayed synergistic inhibition of multidrug-resistant P. aeruginosa in vitro. There was little correlation between combinations that were synergistic in vitro and those that showed enhanced efficacy in vivo versus infected G. mellonella larvae. The most potent dual and triple combinations in vivo were cefotaxime plus piperacillin, and meropenem plus piperacillin and amikacin, respectively. Fewer combinations were found to offer enhanced therapeutic benefit in vivo compared with in vitro. The therapeutic benefit arising from treatment with antibiotic combinations in vivo correlated with reduced larval burden of P. aeruginosa. This study has identified antibiotic combinations that merit further investigation for their clinical potential and has demonstrated the utility of using G. mellonella to screen for novel antibiotic treatments that demonstrate efficacy in vivo.

  2. Gallium-Protoporphyrin IX Inhibits Pseudomonas aeruginosa Growth by Targeting Cytochromes

    Science.gov (United States)

    Hijazi, Sarah; Visca, Paolo; Frangipani, Emanuela

    2017-01-01

    Pseudomonas aeruginosa is a challenging pathogen due to both innate and acquired resistance to antibiotics. It is capable of causing a variety of infections, including chronic lung infection in cystic fibrosis (CF) patients. Given the importance of iron in bacterial physiology and pathogenicity, iron-uptake and metabolism have become attractive targets for the development of new antibacterial compounds. P. aeruginosa can acquire iron from a variety of sources to fulfill its nutritional requirements both in the environment and in the infected host. The adaptation of P. aeruginosa to heme iron acquisition in the CF lung makes heme utilization pathways a promising target for the development of new anti-Pseudomonas drugs. Gallium [Ga(III)] is an iron mimetic metal which inhibits P. aeruginosa growth by interfering with iron-dependent metabolism. The Ga(III) complex of the heme precursor protoporphyrin IX (GaPPIX) showed enhanced antibacterial activity against several bacterial species, although no inhibitory effect has been reported on P. aeruginosa. Here, we demonstrate that GaPPIX is indeed capable of inhibiting the growth of clinical P. aeruginosa strains under iron-deplete conditions, as those encountered by bacteria during infection, and that GaPPIX inhibition is reversed by iron. Using P. aeruginosa PAO1 as model organism, we show that GaPPIX enters cells through both the heme-uptake systems has and phu, primarily via the PhuR receptor which plays a crucial role in P. aeruginosa adaptation to the CF lung. We also demonstrate that intracellular GaPPIX inhibits the aerobic growth of P. aeruginosa by targeting cytochromes, thus interfering with cellular respiration.

  3. A proof-of-concept model for the identification of the key events in the infection process with specific reference to Pseudomonas aeruginosa in corneal infections

    Directory of Open Access Journals (Sweden)

    Ilias Soumpasis

    2015-11-01

    Full Text Available Background: It is a common medical practice to characterise an infection based on the causative agent and to adopt therapeutic and prevention strategies targeting the agent itself. However, from an epidemiological perspective, exposure to a microbe can be harmless to a host as a result of low-level exposure or due to host immune response, with opportunistic infection only occurring as a result of changes in the host, pathogen, or surrounding environment. Methods: We have attempted to review systematically the key host, pathogen, and environmental factors that may significantly impact clinical outcomes of exposure to a pathogen, using Pseudomonas aeruginosa eye infection as a case study. Results and discussion: Extended contact lens wearing and compromised hygiene may predispose users to microbial keratitis, which can be a severe and vision-threatening infection. P. aeruginosa has a wide array of virulence-associated genes and sensing systems to initiate and maintain cell populations at the corneal surface and beyond. We have adapted the well-known concept of the epidemiological triangle in combination with the classic risk assessment framework (hazard identification, characterisation, and exposure to develop a conceptual pathway-based model that demonstrates the overlapping relationships between the host, the pathogen, and the environment; and to illustrate the key events in P. aeruginosa eye infection. Conclusion: This strategy differs from traditional approaches that consider potential risk factors in isolation, and hopefully will aid the identification of data and models to inform preventive and therapeutic measures in addition to risk assessment. Furthermore, this may facilitate the identification of knowledge gaps to direct research in areas of greatest impact to avert or mitigate adverse outcomes of infection.

  4. A proof-of-concept model for the identification of the key events in the infection process with specific reference to Pseudomonas aeruginosa in corneal infections

    Science.gov (United States)

    Soumpasis, Ilias; Knapp, Laura; Pitt, Tyrone

    2015-01-01

    Background It is a common medical practice to characterise an infection based on the causative agent and to adopt therapeutic and prevention strategies targeting the agent itself. However, from an epidemiological perspective, exposure to a microbe can be harmless to a host as a result of low-level exposure or due to host immune response, with opportunistic infection only occurring as a result of changes in the host, pathogen, or surrounding environment. Methods We have attempted to review systematically the key host, pathogen, and environmental factors that may significantly impact clinical outcomes of exposure to a pathogen, using Pseudomonas aeruginosa eye infection as a case study. Results and discussion Extended contact lens wearing and compromised hygiene may predispose users to microbial keratitis, which can be a severe and vision-threatening infection. P. aeruginosa has a wide array of virulence-associated genes and sensing systems to initiate and maintain cell populations at the corneal surface and beyond. We have adapted the well-known concept of the epidemiological triangle in combination with the classic risk assessment framework (hazard identification, characterisation, and exposure) to develop a conceptual pathway-based model that demonstrates the overlapping relationships between the host, the pathogen, and the environment; and to illustrate the key events in P. aeruginosa eye infection. Conclusion This strategy differs from traditional approaches that consider potential risk factors in isolation, and hopefully will aid the identification of data and models to inform preventive and therapeutic measures in addition to risk assessment. Furthermore, this may facilitate the identification of knowledge gaps to direct research in areas of greatest impact to avert or mitigate adverse outcomes of infection. PMID:26546946

  5. Evaluation of antibiotic efficacy against infections caused by planktonic or biofilm cultures of Pseudomonas aeruginosa and Klebsiella pneumoniae in Galleria mellonella.

    Science.gov (United States)

    Benthall, Gabriel; Touzel, Rebecca E; Hind, Charlotte K; Titball, Richard W; Sutton, J Mark; Thomas, Rachael J; Wand, Matthew E

    2015-11-01

    The lack of novel antibiotics for more than a decade has placed increased pressure on existing therapies to combat the emergence of multidrug-resistant (MDR) bacterial pathogens. This study evaluated the Galleria mellonella insect model in determining the efficacy of available antibiotics against planktonic and biofilm infections of MDR Pseudomonas aeruginosa and Klebsiella pneumoniae strains in comparison with in vitro minimum inhibitory concentration (MIC) determination. In general, in vitro analysis agreed with the G. mellonella studies, and susceptibility in Galleria identified different drug resistance mechanisms. However, the carbapenems tested appeared to perform better in vivo than in vitro, with meropenem and imipenem able to clear K. pneumoniae and P. aeruginosa infections with strains that had bla(NDM-1) and bla(VIM) carbapenemases. This study also established an implant model in G. mellonella to allow testing of antibiotic efficacy against biofilm-derived infections. A reduction in antibiotic efficacy of amikacin against K. pneumoniae and P. aeruginosa biofilms was observed compared with a planktonic infection. Ciprofloxacin was found to be less effective at clearing a P. aeruginosa biofilm infection compared with a planktonic infection, but no statistical difference was seen between K. pneumoniae biofilm and planktonic infections treated with this antibiotic (P>0.05). This study provides important information regarding the suitability of Galleria as a model for antibiotic efficacy testing both against planktonic and biofilm-derived MDR infections.

  6. Antimicrobial Susceptibility and Distribution of TEM and CTX-M Genes among ESBL-producing Klebsiella pneumoniae and Pseudomonas aeruginosa Causing Urinary Tract Infections

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    Roya Alavi-Naini

    2014-04-01

    Full Text Available Background: Extended spectrum beta lactamases (ESBLs have been observed in nearly all the species of family Enterobacteriaceae. The enzymes are plasmid mediated and are derived from broad-spectrum beta lactamase TEM and CTX- M by a limited number of mutations. This study was undertaken to characterize ESBL producers among Klebsiella pneumoniae and Pseudomonas aeruginosa by PCR, which were initially screened by phenotypic method. Materials and Methods: A cross-sectional study was performed to evaluate 180 strains (30 K. pneumoniae and 150 P. aeruginosa isolated from urine culture of hospitalized patients (Amir Al-Momenin Hospital, Zabol, south-eastern Iran suffered from urinary tract infections during a period of six months. The prevalence of ESBL producing K. pneumoniae and P. aeruginosa was evaluated by disk diffusion test and polymerase chain reaction (PCR by detecting TEM and CTX-M gene. Results: The results of the study revealed that the prevalence of ESBL producing P. aeruginosa and K. pneumoniae by disk diffusion test was 13.3% for P. aeruginosa and 66.6% for K. pneumoniae. Seventy five percent and 65% of K. pneumoniae harboured the gene TEM and CTX-M, respectively. Forty five percent of P. aeruginosa isolates harboured the gene TEM but none of them demonstrated the gene CTX-M using PCR method. Conclusion: ESBL producing P. aeruginosa and K. pneumoniae isolates showed a high prevalence in this study. Therefore it seems that continuous surveillance is essential to monitor the ESBLs producing microorganisms in hospitals and community

  7. A Genetic Approach to the Development of New Therapeutic Phages to Fight Pseudomonas Aeruginosa in Wound Infections

    Directory of Open Access Journals (Sweden)

    Elena Pleteneva

    2012-12-01

    Full Text Available Pseudomonas aeruginosa is a frequent participant in wound infections. Emergence of multiple antibiotic resistant strains has created significant problems in the treatment of infected wounds. Phage therapy (PT has been proposed as a possible alternative approach. Infected wounds are the perfect place for PT applications, since the basic condition for PT is ensured; namely, the direct contact of bacteria and their viruses. Plenty of virulent (“lytic” and temperate (“lysogenic” bacteriophages are known in P. aeruginosa. However, the number of virulent phage species acceptable for PT and their mutability are limited. Besides, there are different deviations in the behavior of virulent (and temperate phages from their expected canonical models of development. We consider some examples of non-canonical phage-bacterium interactions and the possibility of their use in PT. In addition, some optimal approaches to the development of phage therapy will be discussed from the point of view of a biologist, considering the danger of phage-assisted horizontal gene transfer (HGT, and from the point of view of a surgeon who has accepted the Hippocrates Oath to cure patients by all possible means. It is also time now to discuss the possible approaches in international cooperation for the development of PT. We think it would be advantageous to make phage therapy a kind of personalized medicine.

  8. Hypoxia, innate immunity and infection in the lung.

    LENUS (Irish Health Repository)

    Schaible, Bettina

    2012-02-01

    The mucosal surface of the lung is the key interface between the external atmosphere and the bloodstream. Normally, this well oxygenated tissue is maintained in state of sterility by a number of innate immune processes. These include a physical and dynamic mucus barrier, the production of microbiocidal peptides and the expression of specific pattern recognition receptors on alveolar epithelial cells and resident macrophages and dendritic cells which recognise microbial structures and initiate innate immune responses which promote the clearance of potentially infectious agents. In a range of diseases, the mucosal surface of the lung experiences decreased oxygen tension leading to localised areas of prominent hypoxia which can impact upon innate immune and subsequent infectious and inflammatory processes. Under these conditions, the lung is generally more susceptible to infection and subsequent inflammation. In the current review, we will discuss recent data pertaining to the role of hypoxia in regulating both host and pathogen in the lung during pulmonary disease and how this contributes to innate immunity, infection and inflammation.

  9. Effect of temperature on cystic fibrosis lung disease and infections: a replicated cohort study.

    Directory of Open Access Journals (Sweden)

    Joseph M Collaco

    Full Text Available BACKGROUND: Progressive lung disease accounts for the majority of morbidity and mortality observed in cystic fibrosis (CF. Beyond secondhand smoke exposure and socio-economic status, the effect of specific environmental factors on CF lung function is largely unknown. METHODS: Multivariate regression was used to assess correlation between specific environmental factors, the presence of pulmonary pathogens, and variation in lung function using subjects enrolled in the U.S. CF Twin and Sibling Study (CFTSS: n = 1378. Significant associations were tested for replication in the U.S. CF Foundation Patient Registry (CFF: n = 16439, the Australian CF Data Registry (ACFDR: n = 1801, and prospectively ascertained subjects from Australia/New Zealand (ACFBAL: n = 167. RESULTS: In CFTSS subjects, the presence of Pseudomonas aeruginosa (OR = 1.06 per °F; p<0.001 was associated with warmer annual ambient temperatures. This finding was independently replicated in the CFF (1.02; p<0.001, ACFDR (1.05; p = 0.002, and ACFBAL (1.09; p = 0.003 subjects. Warmer temperatures (-0.34 points per °F; p = 0.005 and public insurance (-6.43 points; p<0.001 were associated with lower lung function in the CFTSS subjects. These findings were replicated in the CFF subjects (temperature: -0.31; p<0.001; insurance: -9.11; p<0.001 and similar in the ACFDR subjects (temperature: -0.23; p = 0.057. The association between temperature and lung function was minimally influenced by P. aeruginosa. Similarly, the association between temperature and P. aeruginosa was largely independent of lung function. CONCLUSIONS: Ambient temperature is associated with prevalence of P. aeruginosa and lung function in four independent samples of CF patients from two continents.

  10. Multiple virulence factors regulated by quorum sensing may help in establishment and colonisation of urinary tract by Pseudomonas aeruginosa during experimental urinary tract infection

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    P Gupta

    2013-01-01

    Full Text Available Purpose: Damage caused by an organism during infection is attributed to production of virulence factors. Different virulence factors produced by the organism contribute to its pathogenicity, individually. During infectious conditions, role of virulence factors produced by the pathogen is different, depending upon the site of involvement. Pseudomonas aeruginosa is an opportunistic nosocomial pathogen known to cause infections of the respiratory tract, burn wound, urinary tract and eye. Importance of virulence factors produced by P. Aeruginosa during infections such as keratitis, burn wound and respiratory tract is known. The present study was designed to understand the importance of different virulence factors of P. aeruginosa in urinary tract infection in vivo. Materials and methods: An ascending urinary tract infection model was established in mice using standard parent strain PAO1 and its isogenic mutant, JP2. Mice were sacrificed at different time intervals and renal tissue homogenates were used for estimation of renal bacterial load and virulence factors. Results: Both parent and mutant strains were able to reach the renal tissue. PAO 1 PAO1was isolated from renal tissue till day 5 post-infection. However, the mutant strain was unable to colonise the renal tissue. Failure of mutant strain to colonise was attributed to its inability to produce protease, elastase and rhamnolipid. Conclusion: This study suggests that protease, elastase and rhamnolipid contribute to pathogenesis and survival of P. aeruginosa during urinary tract infection.

  11. Influence of Pseudomonas aeruginosa on exacerbation in patients with bronchiectasis

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    Kiran Chawla

    2015-01-01

    Full Text Available Background: A majority of the studies done on the western population have shown that Pseudomonas aeruginosa causes many severe infections in patients with bronchiectasis as compared to other pathogens. There is scarcity of similar data from the Asian population. Materials and Methods: A prospective study was undertaken to identify the various pathogens isolated from the respiratory samples of 117 patients with bronchiectasis from south India and to compare the clinicomicrobiological profile of infections caused by P. aeruginosa and other respiratory pathogens. Results: The respiratory pathogens were isolated from 63 (53.8% patients. P. aeruginosa was the most common isolate (46.0% followed by Klebsiella pneumoniae (14.3% and other pathogenic bacteria. Patients included in the P. aeruginosa group had a higher number of exacerbations (p: 0.008, greater number of hospital admissions (p: 0.007, a prolonged hospital stay (p: 0.03, and poor lung function, compared to the patients infected with the non-Pseudomonas group. Conclusion: It is necessary to investigate the etiology of respiratory tract infections among bronchiectasis patients followed by the prompt management of cases diagnosed with P. aeruginosa infections, so as to lower the morbidity and have a better prognosis.

  12. MUC18 Regulates Lung Rhinovirus Infection and Inflammation

    Science.gov (United States)

    Berman, Reena; Jiang, Di; Wu, Qun; Stevenson, Connor R.; Schaefer, Niccolette R.; Chu, Hong Wei

    2016-01-01

    Background MUC18 is upregulated in the lungs of asthma and COPD patients. It has been shown to have pro-inflammatory functions in cultured human airway epithelial cells during viral infections and in mice during lung bacterial infections. However, the in vivo role of MUC18 in the context of viral infections remains poorly understood. The goal of this study is to define the in vivo function of MUC18 during respiratory rhinovirus infection. Methods Muc18 wild-type (WT) and knockout (KO) mice were infected with human rhinovirus 1B (HRV-1B) and sacrificed after 1 day to determine the inflammatory and antiviral responses. To examine the direct effects of Muc18 on viral infection, tracheal epithelial cells isolated from WT and KO mice were grown under air-liquid interface and infected with HRV-1B. Finally, siRNA mediated knockdown of MUC18 was performed in human airway epithelial cells (AECs) to define the impact of MUC18 on human airway response to HRV-1B. Results Both viral load and neutrophilic inflammation were significantly decreased in Muc18 KO mice compared to WT mice. In the in vitro setting, viral load was significantly lower and antiviral gene expression was higher in airway epithelial cells of Muc18 KO mice than the WT mice. Furthermore, in MUC18 knockdown human AECs, viral load was decreased and antiviral gene expression was increased compared to controls. Conclusions Our study is the first to demonstrate MUC18’s pro-inflammatory and pro-viral function in an in vivo mouse model of rhinovirus infection. PMID:27701461

  13. Nasal immunization with Burkholderia multivorans outer membrane proteins and the mucosal adjuvant adamantylamide dipeptide confers efficient protection against experimental lung infections with B. multivorans and B. cenocepacia.

    Science.gov (United States)

    Bertot, Gustavo M; Restelli, Marcela A; Galanternik, Laura; Aranibar Urey, Rene C; Valvano, Miguel A; Grinstein, Saúl

    2007-06-01

    Chronic lung infection by opportunistic pathogens, such as Pseudomonas aeruginosa and members of the Burkholderia cepacia complex, is a major cause of morbidity and mortality in patients with cystic fibrosis. Outer membrane proteins (OMPs) of gram-negative bacteria are promising vaccine antigen candidates. In this study, we evaluated the immunogenicity, protection, and cross-protection conferred by intranasal vaccination of mice with OMPs from B. multivorans plus the mucosal adjuvant adamantylamide dipeptide (AdDP). Robust mucosal and systemic immune responses were stimulated by vaccination of naive animals with OMPs from B. multivorans and B. cenocepacia plus AdDP. Using a mouse model of chronic pulmonary infection, we observed enhanced clearance of B. multivorans from the lungs of vaccinated animals, which correlated with OMP-specific secretory immunoglobulin A responses. Furthermore, OMP-immunized mice showed rapid resolution of the pulmonary infection with virtually no lung pathology after bacterial challenge with B. multivorans. In addition, we demonstrated that administration of B. multivorans OMP vaccine conferred protection against B. cenocepacia challenge in this mouse infection model, suggesting that OMPs provide cross-protection against the B. cepacia complex. Therefore, we concluded that mucosal immunity to B. multivorans elicited by intranasal vaccination with OMPs plus AdDP could prevent early steps of colonization and infection with B. multivorans and also ameliorate lung tissue damage, while eliciting cross-protection against B. cenocepacia. These results support the notion that therapies leading to increased mucosal immunity in the airways may help patients with cystic fibrosis.

  14. Nasal Immunization with Burkholderia multivorans Outer Membrane Proteins and the Mucosal Adjuvant Adamantylamide Dipeptide Confers Efficient Protection against Experimental Lung Infections with B. multivorans and B. cenocepacia▿

    Science.gov (United States)

    Bertot, Gustavo M.; Restelli, Marcela A.; Galanternik, Laura; Aranibar Urey, Rene C.; Valvano, Miguel A.; Grinstein, Saúl

    2007-01-01

    Chronic lung infection by opportunistic pathogens, such as Pseudomonas aeruginosa and members of the Burkholderia cepacia complex, is a major cause of morbidity and mortality in patients with cystic fibrosis. Outer membrane proteins (OMPs) of gram-negative bacteria are promising vaccine antigen candidates. In this study, we evaluated the immunogenicity, protection, and cross-protection conferred by intranasal vaccination of mice with OMPs from B. multivorans plus the mucosal adjuvant adamantylamide dipeptide (AdDP). Robust mucosal and systemic immune responses were stimulated by vaccination of naive animals with OMPs from B. multivorans and B. cenocepacia plus AdDP. Using a mouse model of chronic pulmonary infection, we observed enhanced clearance of B. multivorans from the lungs of vaccinated animals, which correlated with OMP-specific secretory immunoglobulin A responses. Furthermore, OMP-immunized mice showed rapid resolution of the pulmonary infection with virtually no lung pathology after bacterial challenge with B. multivorans. In addition, we demonstrated that administration of B. multivorans OMP vaccine conferred protection against B. cenocepacia challenge in this mouse infection model, suggesting that OMPs provide cross-protection against the B. cepacia complex. Therefore, we concluded that mucosal immunity to B. multivorans elicited by intranasal vaccination with OMPs plus AdDP could prevent early steps of colonization and infection with B. multivorans and also ameliorate lung tissue damage, while eliciting cross-protection against B. cenocepacia. These results support the notion that therapies leading to increased mucosal immunity in the airways may help patients with cystic fibrosis. PMID:17296759

  15. Quantitative analysis of the IgG and IgG subclass immune responses to chromosomal Pseudomonas aeruginosa beta-lactamase in serum from patients with cystic fibrosis by western blotting and laser scanning densitometry

    DEFF Research Database (Denmark)

    Petersen, T D; Ciofu, O; Pressler, T

    1996-01-01

    BACKGROUND: Antibodies against chromosomal beta-lactamase of Pseudomonas aeruginosa (a beta ab) are markers of the development of resistance of P aeruginosa to beta-lactam antibiotics in patients with cystic fibrosis and chronic lung infection. The role of these antibodies in patients with chronic...

  16. Pseudomonas aeruginosa in Healthcare Settings

    Science.gov (United States)

    ... Address What's this? Submit What's this? Submit Button Pseudomonas aeruginosa in Healthcare Settings Recommend on Facebook Tweet ... and/or help treat infections? What is a Pseudomonas infection? Pseudomonas infection is caused by strains of ...

  17. 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....

  18. Effectiveness of netilmicin and tobramycin against Pseudomonas aeruginosa in vitro and in an experimental tissue infection in mice.

    Science.gov (United States)

    Moffie, B G; Hoogeterp, J J; Lim, T; Douwes-Idema, A E; Mattie, H

    1993-03-01

    The activity of netilmicin and tobramycin against Pseudomonas aeruginosa was assessed in vitro in the presence of constant and exponentially declining concentrations, and in mice in an experimental thigh infection. The activity in vitro at constant concentrations was expressed as the maximal killing rate (ER) during 3 h of exposure. On the basis of the quantitative relation between E(R) and the drug concentration, the numbers of cfu expected at consecutive times, at constant as well as at declining concentrations, were predicted. The relationship between observed numbers and predicted values of ERt were similar under both conditions for both drugs. On the same basis the numbers of cfu expected in the experimental thigh infection were predicted. There was indeed a significant linear relationship between observed numbers of cfu in homogenized muscle and the values predicted on the basis of the pharmacokinetics of the aminoglycosides, but the slope of this relationship was only 0.22. There was no difference in this respect between the two antibiotics. It is concluded that the efficacy of netilmicin and tobramycin against P. aeruginosa is considerably less in vivo than in vitro, but the relation is about the same for the two drugs; therefore the slightly higher activity of tobramycin in vitro is relevant in the in-vivo situation.

  19. Pseudomonas aeruginosa necrotizing infection of the abdominal flap in a post-bariatric patient undergoing body contouring surgery.

    Science.gov (United States)

    Araco, Antonino; Araco, Francesco; Abdullah, Parveen; Overton, John; Gravante, Gianpiero

    2009-06-01

    Pseudomonas aeruginosa infections may involve any organ or body district and may give serious clinical sequelae. We report the case of an infection of the abdominoplasty flap that compromised wound closure and jeopardized the aesthetic outcome. To the best of our knowledge, this is the first such case reported in the literature for this group of patients. We have presented this case in order to alert plastic and general surgeons who may encounter this complication in future, such that they may be aware of the need to adopt an aggressive approach to manage these patients. This consisted of the accurate monitoring of the patient's clinical condition, prescribing appropriate antibiotics, and performing serial debridement of necrotic tissue.

  20. Next-Generation "-omics" Approaches Reveal a Massive Alteration of Host RNA Metabolism during Bacteriophage Infection of Pseudomonas aeruginosa.

    Directory of Open Access Journals (Sweden)

    Anne Chevallereau

    2016-07-01

    Full Text Available As interest in the therapeutic and biotechnological potentials of bacteriophages has grown, so has value in understanding their basic biology. However, detailed knowledge of infection cycles has been limited to a small number of model bacteriophages, mostly infecting Escherichia coli. We present here the first analysis coupling data obtained from global next-generation approaches, RNA-Sequencing and metabolomics, to characterize interactions between the virulent bacteriophage PAK_P3 and its host Pseudomonas aeruginosa. We detected a dramatic global depletion of bacterial transcripts coupled with their replacement by viral RNAs over the course of infection, eventually leading to drastic changes in pyrimidine metabolism. This process relies on host machinery hijacking as suggested by the strong up-regulation of one bacterial operon involved in RNA processing. Moreover, we found that RNA-based regulation plays a central role in PAK_P3 lifecycle as antisense transcripts are produced mainly during the early stage of infection and viral small non coding RNAs are massively expressed at the end of infection. This work highlights the prominent role of RNA metabolism in the infection strategy of a bacteriophage belonging to a new characterized sub-family of viruses with promising therapeutic potential.

  1. Isolation of human β-defensin-4 in lung tissue and its increase in lower respiratory tract infection

    Directory of Open Access Journals (Sweden)

    Mukae Hiroshi

    2005-11-01

    Full Text Available Abstract Background Human β-defensin-4 (hBD-4, a new member of the β-defensin family, was discovered by an analysis of the genomic sequence. The objective of this study was to clarify hBD-4 expression in human lung tissue, along with the inducible expression in response to infectious stimuli, localization, and antimicrobial activities of hBD-4 peptides. We also investigated the participation of hBD-4 in chronic lower respiratory tract infections (LRTI by measuring the concentrations of hBD-4 peptides in human bronchial epithelial lining fluid (ELF. Methods The antimicrobial activity of synthetic hBD-4 peptides against E. coli and P. aeruginosa was measured by radial diffusion and colony count assays. We identified hBD-4 in homogenated human lung tissue by reverse-phase high-performance liquid chromatography coupled with a radioimmunoassay (RIA. Localization of hBD-4 was studied through immunohistochemical analysis (IHC. We investigated the effects of lipopolysaccharide (LPS on hBD-4 expression and its release from small airway epithelial cells (SAEC. We collected ELF from patients with chronic LRTI using bronchoscopic microsampling to measure hBD-4 concentrations by RIA. Results hBD-4 exhibited salt-sensitive antimicrobial activity against P. aeruginosa. We detected the presence of hBD-4 peptides in human lung tissue. IHC demonstrated the localization of hBD-4-producing cells in bronchial and bronchiolar epithelium. The levels of hBD-4 peptides released from LPS-treated SAECs were higher than those of untreated control cells. ELF hBD-4 was detectable in 4 of 6 patients with chronic LRTI, while the amounts in controls were all below the detectable level. Conclusion This study suggested that hBD-4 plays a significant role in the innate immunity of the lower respiratory tract.

  2. Innate immune response to viral infection of the lungs.

    Science.gov (United States)

    See, Hayley; Wark, Peter

    2008-12-01

    Viral respiratory tract infections are the most common infectious illnesses, though they are usually self-limiting and confined to the respiratory tract. The rapid identification of viruses and their effective elimination with minimal local and systemic inflammation is a testament to the efficiency of the innate immune response within the airways and lungs. A failure of this response appears to occur in those with asthma and chronic obstructive pulmonary disease, where viral infection is an important trigger for acute exacerbations. The innate immune response to viruses requires their early detection through pathogen recognition receptors and the recruitment of the efficient antiviral response that is centred around the release of type 1 interferons. The airway epithelium provides both a barrier and an early detector for viruses, and interacts closely with cells of the innate immune response, especially macrophages and dendritic cells, to eliminate infection and trigger a specific adaptive immune response.

  3. Epidemiology of Pseudomonas aeruginosa in cystic fibrosis and the possible role of contamination by dental equipment

    DEFF Research Database (Denmark)

    Jensen, E T; Giwercman, B; Ojeniyi, B;

    1997-01-01

    Cystic fibrosis (CF) patients often suffer from Pseudomonas aeruginosa lung infection yet the source of this organism is not known. In order to determine whether CF patients might be contaminated with P. aeruginosa from dental equipment, a total of 103 water samples from 25 dental sessions...... in Frederiksberg Municipal Oral Health Care Service were examined. Three samples (2.9%) were positive for P. aeruginosa. Three hundred and twenty-seven water samples from 82 dental sessions from various other Municipal Oral Health Services in Denmark, attended by CF patients, were also examined. Eighteen of 327...... samples (5.5%) from nine sessions (11%) were positive for P. aeruginosa. In one case, genotypically identical (RFLP, pulsed-field gel electrophoresis) P. aeruginosa strains were found both in water from the dental equipment and in the CF patients sputum. This indicates a small risk for acquiring P...

  4. Dynamics and spatial distribution of beta-lactamase expression in Pseudomonas aeruginosa biofilms

    DEFF Research Database (Denmark)

    Bagge, N.; Hentzer, Morten; Andersen, Jens Bo

    2004-01-01

    The development of resistance to beta-lactam antibiotics is a problem in the treatment of chronic Pseudomonas aeruginosa infection in the lungs of patients with cystic fibrosis. The main resistance mechanism is high-level expression of the chromosomally encoded AmpC beta-lactamase of P. aeruginosa...... cells growing in biofilms. Several genes have been shown to influence the level of ampC expression, but little is known about the regulation of ampC expression in P. aeruginosa biofilms. To study the expression of ampC in P. aeruginosa biofilms, we constructed a reporter that consisted of the fusion...... of the ampC promoter to gfp(ASV) encoding an unstable version of the green fluorescent protein. In vitro biofilms of P. aeruginosa were exposed to the beta-lactam antibiotics imipenem and ceftazidime. Sub-MICs of imipenem significantly induced the monitor system of the biofilm bacteria in the peripheries...

  5. Review: Antibiotic discovery in the age of structural biology - a comprehensive overview with special reference to development of drugs for the treatment of Pseudomonas aeruginosa infection.

    Science.gov (United States)

    Koehnke, Alessa; Friedrich, Reinhard E

    2015-01-01

    Due to the persistence and spread of antibiotic resistance, the discovery and exploitation of new antibiotic targets should be the subject of intensive research. Effective strategies are required to develop antibiotic alternatives. Antibiotics that act on new targets or via novel mechanisms have the greatest likelihood of overcoming resistance. In particular, there is a lack of specific antibiotics for Pseudomonas aeruginosa, one of the leading causes of healthcare-associated infections, exhibiting high resistance levels. Herein we describe how structure-based drug design can be used to achieve new antibiotics for the treatment of Pseudomonas aeruginosa infection, using an essential enzyme of the fatty acid synthesis pathway from P. aeruginosa as an example.

  6. Panax ginseng has anti-infective activity against opportunistic pathogen Pseudomonas aeruginosa by inhibiting quorum sensing, a bacterial communication process critical for establishing infection

    DEFF Research Database (Denmark)

    Song, Z; Kong, K F; Wu, H

    2010-01-01

    Virulent factors produced by pathogens play an important role in the infectious process, which is regulated by a cell-to-cell communication mechanism called quorum sensing (QS). Pseudomonas aeruginosa is an important opportunistic human pathogen, which causes infections in patients with compromised...... of ginseng are mutually exclusive as it is a complex mixture, as shown with the HPLC analysis of the hot water extract. Though ginseng is a promising natural synergetic remedy, it is important to isolate and evaluate the ginseng compounds associated with the anti-QS activity....

  7. Prospective Multicenter Study of the Impact of Carbapenem Resistance on Mortality in Pseudomonas aeruginosa Bloodstream Infections

    OpenAIRE

    2012-01-01

    The impact of antimicrobial resistance on clinical outcomes is the subject of ongoing investigations, although uncertainty remains about its contribution to mortality. We investigated the impact of carbapenem resistance on mortality in Pseudomonas aeruginosa bacteremia in a prospective multicenter (10 teaching hospitals) observational study of patients with monomicrobial bacteremia followed up for 30 days after the onset of bacteremia. The adjusted influence of carbapenem resistance on mortal...

  8. Modeling Granulomas in Response to Infection in the Lung.

    Directory of Open Access Journals (Sweden)

    Wenrui Hao

    Full Text Available Alveolar macrophages play a large role in the innate immune response of the lung. However, when these highly immune-regulatory cells are unable to eradicate pathogens, the adaptive immune system, which includes activated macrophages and lymphocytes, particularly T cells, is called upon to control the pathogens. This collection of immune cells surrounds, isolates and quarantines the pathogen, forming a small tissue structure called a granuloma for intracellular pathogens like Mycobacterium tuberculosis (Mtb. In the present work we develop a mathematical model of the dynamics of a granuloma by a system of partial differential equations. The 'strength' of the adaptive immune response to infection in the lung is represented by a parameter α, the flux rate by which T cells and M1 macrophages that immigrated from the lymph nodes enter into the granuloma through its boundary. The parameter α is negatively correlated with the 'switching time', namely, the time it takes for the number of M1 type macrophages to surpass the number of infected, M2 type alveolar macrophages. Simulations of the model show that as α increases the radius of the granuloma and bacterial load in the granuloma both decrease. The model is used to determine the efficacy of potential host-directed therapies in terms of the parameter α, suggesting that, with fixed dosing level, an infected individual with a stronger immune response will receive greater benefits in terms of reducing the bacterial load.

  9. 铜绿假单胞菌相关性肺损伤的蛋白质差异表达研究%Differential expression of proteins in Pseudomonas aeruginosa-induced acute lung injury

    Institute of Scientific and Technical Information of China (English)

    刘冬冬; 毛璞; 廖东江; 余志辉; 杨淳; 黄红川; 刘晓青; 何为群; 黎毅敏

    2011-01-01

    Objective To screen the differential expressed proteins of Pseudomonas aeruginosainduced acute lung injury by proteomics, and to provide the theoretical basis for the identification of acute lung injury caused by bacterial infection and non-infection. Methods The rat models of Pseudomonas aeruginosa -induced acute lung injury and non-infection-induced acute lung injury (including ventilatorinduced acute lung injury and oleic acid-induced acute lung injury) were established. The total proteins were extracted and separated by two-dimensional gel electrophoresis (2-DE). The sites of differential expression were analyzed using Image Master 2D Elite 5. 0 image analysis software,and the peptide mass finger-printing was identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). The biological information of these proteins was searched in the NCBI database and confirmed by Western blot. Results Thirty-two differential expression protein spots were found in 2-DE maps, and eighteen proteins were analyzed and identified by MALDI-TOF-MS. Eleven proteins (including peroxiredoxin Ⅰ . calreticulin etc. ) were upregulated while seven proteins (including glutathione-S-transferaseα4. transthyretin etc. ) were downregulated in Pseudomonas aeruginosa -induced acute lung injury group. The upregulated expression of peroxiredoxin Ⅰ in Pseudomonas aeruginosainduced acute lung injury group was confirmed by Western blot. Conclusions Eighteen different proteins were identified by comparative proteomics, and involved in catalytic metabolism, redox, signal transduction. Eleven proteins were upregulated and seven proteins were downregulated in Pseudomonas aeruginosa-induced acute lung injury group. Peroxiredoxin Ⅰ and calreticulin may play an important role in bacterial infected-acute lung injury by regulating oxidant/antioxidant and immune response.%目的 利用蛋白质组学方法筛选铜绿假单胞菌急性肺损伤特异相关蛋

  10. 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.

  11. Genomic and Transcriptional Mapping of PaMx41, Archetype of a New Lineage of Bacteriophages Infecting Pseudomonas aeruginosa.

    Science.gov (United States)

    Cruz-Plancarte, Indira; Cazares, Adrián; Guarneros, Gabriel

    2016-11-15

    Previously, a collection of virulent phages infecting Pseudomonas aeruginosa was isolated from open water reservoirs and residual waters. Here, we described the comparative genomics of a set of five related phages from the collection, the physical structure of the genome, the structural proteomics of the virion, and the transcriptional program of archetypal phage PaMx41. The phage genomes were closely associated with each other and with those of two other P. aeruginosa phages, 119X and PaP2, which were previously filed in the databases. Overall, the genomes were approximately 43 kb, harboring 53 conserved open reading frames (ORFs) and three short ORFs in indel regions and containing 45% GC content. The genome of PaMx41 was further characterized as a linear, terminally redundant DNA molecule. A total of 16 ORFs were associated with putative functions, including nucleic acid metabolism, morphogenesis, and lysis, and eight virion proteins were identified through mass spectrometry. However, the coding sequences without assigned functions represent 70% of the ORFs. The PaMx41 transcription program was organized in early, middle, and late expressed genomic modules, which correlated with regions containing functionally related genes. The high genomic conservation among these distantly isolated phages suggests that these viruses undergo selective pressure to remain unchanged. The 119X lineage represents a unique set of phages that corresponds to a novel phage group. The features recognized in the genomes and the broad host range of clinical strains suggest that these phages are candidates for therapy applications.

  12. Cultivation and characterization of the MaMV-DC cyanophage that infects bloom-forming cyanobacterium Microcystis aeruginosa.

    Science.gov (United States)

    Ou, Tong; Li, Sanhua; Liao, Xiangyong; Zhang, Qiya

    2013-10-01

    The MaMV-DC cyanophage, which infects the bloom-forming cyanobacterium Microcystis aeruginosa, was isolated from Lake Dianchi, Kunming, China. Twenty-one cyanobacterial strains were used to detect the host range of MaMV-DC. Microcystic aeruginosa FACHB-524 and plaque purification were used to isolate individual cyanophages, and culturing MaMV-DC with cyanobacteria allowed us to prepare purified cyanophages for further analysis. Electron microscopy demonstrated that the negatively stained viral particles are tadpole-shaped with an icosahedral head approximately 70 nm in diameter and a contractile tail approximately 160 nm in length. Using one-step growth experiments, the latent period and burst size of MaMV-DC were estimated to be 24-48 hours and approximately 80 infectious units per cell, respectively. Restriction endonuclease digestion and agarose gel electrophoresis were performed using purified MaMV-DC genomic DNA, and the genome size was estimated to be approximately 160 kb. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis revealed four major structural proteins. These results support the growing interest in using freshwater cyanophages to control bloom-forming cyanobacterium.

  13. Comparison of severity of illness scoring systems for patients with nosocomial bloodstream infection due to Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Wenzel Richard P

    2006-08-01

    Full Text Available Abstract Background Several acute illness severity scores have been proposed for evaluating patients on admission to intensive care units but these have not been compared for patients with nosocomial bloodstream infection (nBSI. We compared three severity of illness scoring systems for predicting mortality in patients with nBSI due to Pseudomonas aeruginosa. Methods We performed a historical cohort study on 63 adults in intensive care units with P. aeruginosa monomicrobial nBSI. Results The Acute Physiology, Age, Chronic Health Evaluation II (APACHE II, Sequential Organ Failure Assessment (SOFA, and Simplified Acute Physiologic Score (SAPS II, were calculated daily from 2 days prior through 2 days after the first positive blood culture. Calculation of the area under the receiver operating characteristic (ROC curve confirmed that APACHE II and SAPS II at day -1 and SOFA at day +1 were better predictors of outcome than days -2, 0 and day 2 of BSI. By stepwise logistic regression analysis of these three scoring systems, SAPS II (OR: 13.03, CI95% 2.51–70.49 and APACHE II (OR: 12.51, CI95% 3.12–50.09 on day -1 were the best predictors for mortality. Conclusion SAPS II and APACHE II are more accurate than the SOFA score for predicting mortality in this group of patients at day -1 of BSI.

  14. Prevention of catheter-related Pseudomonas aeruginosa infection by levofloxacin-impregnated catheters in vitro and in vivo

    Institute of Scientific and Technical Information of China (English)

    Yan Ping; Liu Wei; Kong Jinliang; Wu Hong; Chen Yiqiang

    2014-01-01

    Background Implanted medical catheter-related infections are increasing,hence a need for developing catheter polymers bonded to antimicrobials.We evaluated preventive effects of levofloxacin-impregnated catheters in catheterrelated Psuedomonas aeruginosa (strain PAO1) infection.Methods Drug release from levofloxacin-impregnated catheters was measured in vitro.Levofloxacin-impregnated catheters and polyvinyl chloride (PVC) catheters were immersed in 5 ml 50% Luria Bertani medium containing 108 CFU/ml Pseudomonas aeruginosa then incubated for 6,12,24 or 48 hours at 37℃ when bacteria adhering to the catheters and bacteria in the growth culture medium were determined.Impregnated and PVC catheters were singly implanted subcutaneously in mice,50 μl (107CFU) of PAO1 was injected into catheters.After the first and fifth days challenge,bacterial counts on implanted catheters and in surrounding tissues were determined microbiologically.Bacterial colonization and biofilm formation on implanted catheters were assessed by scanning electron microscopy.Results Drug release from levofloxacin-impregnated catheters was rapid.Levofloxacin-impregnated catheters had significantly fewer bacteria compared to PVC in vitro.After first and fifth day of challenge,no or significantly fewer bacteria adhered to impregnated catheters or in surrounding tissues compared to PVC.Scanning electron microscopical images after first day displayed from none to significantly fewer bacteria adhering to impregnated implanted catheters,compared to bacteria and microcolonies adhering to PVC catheters.After the fifth day,no bacteria were found on impregnated catheters,compared to clusters surrounding mucus-like substance and coral-shaped biofilms with polymorphonuclear leukocyte on PVC catheters.After the first day of challenge,secretion occurred in all implanted catheters with surrounding tissues mildly hyperaemic and swollen.After the fifth day,minute secretions inside impregnated catheters and no

  15. 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.

  16. Inflammation in Achromobacter xylosoxidans infected cystic fibrosis patients

    DEFF Research Database (Denmark)

    Hansen, C. R.; Pressler, T.; Nielsen, K. G.;

    2010-01-01

    BACKGROUND: Achromobacter xylosoxidans infection may cause conspicuous chronic pulmonary inflammation in cystic fibrosis (CF) patients similar to Pseudomonas aeruginosa and the Burkholderia cepacia complex (Bcc). Evolution in lung function was compared in chronically infected patients. Cytokine...... patients. CONCLUSION: A. xylosoxidans can cause a level of inflammation similar to P. aeruginosa in chronically infected CF patients. A. xylosoxidans is a clinically important pathogen in CF and should be treated accordingly....

  17. Impact of alginate-producing Pseudomonas aeruginosa on alveolar macrophage apoptotic cell clearance.

    Science.gov (United States)

    McCaslin, Charles A; Petrusca, Daniela N; Poirier, Christophe; Serban, Karina A; Anderson, Gregory G; Petrache, Irina

    2015-01-01

    Pseudomonas aeruginosa infection is a hallmark of lung disease in cystic fibrosis. Acute infection with P. aeruginosa profoundly inhibits alveolar macrophage clearance of apoptotic cells (efferocytosis) via direct effect of virulence factors. During chronic infection, P. aeruginosa evades host defense by decreased virulence, which includes the production or, in the case of mucoidy, overproduction of alginate. The impact of alginate on innate immunity, in particular on macrophage clearance of apoptotic cells is not known. We hypothesized that P. aeruginosa strains that exhibit reduced virulence impair macrophage clearance of apoptotic cells and we investigated if the polysaccharide alginate produced by mucoid P. aeruginosa is sufficient to inhibit alveolar macrophage efferocytosis. Rat alveolar or human peripheral blood monocyte (THP-1)-derived macrophage cell lines were exposed in vitro to exogenous alginate or to wild type or alginate-overproducing mucoid P. aeruginosa prior to challenge with apoptotic human Jurkat T-lymphocytes. The importance of LPS contamination and that of structural integrity of alginate polymers was tested using alginate of different purities and alginate lyase, respectively. Alginate inhibited alveolar macrophage efferocytosis in a dose- and time-dependent manner. This effect was augmented but not exclusively attributed to lipopolysaccharide (LPS) present in alginates. Alginate-producing P. aeruginosa inhibited macrophage efferocytosis by more than 50%. A mannuronic-specific alginate lyase did not restore efferocytosis inhibited by exogenous guluronic-rich marine alginate, but had a marked beneficial effect on efferocytosis of alveolar macrophages exposed to mucoid P. aeruginosa. Despite decreased virulence, mucoid P. aeruginosa may contribute to chronic airway inflammation through significant inhibition of alveolar clearance of apoptotic cells and debris. The mechanism by which mucoid bacteria inhibit efferocytosis may involve alginate

  18. MIP-1alpha regulates CD4+ T cell chemotaxis and indirectly enhances PMN persistence in Pseudomonas aeruginosa corneal infection.

    Science.gov (United States)

    Kernacki, K A; Barrett, R P; McClellan, S; Hazlett, L D

    2001-12-01

    The role of macrophage inflammatory protein-1alpha (MIP-1alpha) in cell infiltration into Pseudomonas aeruginosa-infected cornea and subsequent disease was examined. Greater amounts of the chemokine (protein and mRNA) were found in the infected cornea of susceptible B6 ("cornea perforates") versus resistant BALB/c ("cornea heals") mice from 1 to 5 days postinfection. Treatment of BALB/c mice with recombinant (r) MIP-1alpha exacerbated disease and was associated with an increased number of neutrophils (PMNs) in the cornea. Treatment of BALB/c mice with rMIP-1alpha also induced recruitment of activated CD4+ T cells into the affected cornea, converting resistant to susceptible mice. Depleting CD4+ T cells in r-treated BALB/c mice significantly decreased PMNs in cornea tissue, suggesting that T cells regulate persistence of PMNs at this site. In B6 mice, administration of neutralizing MIP-1alpha polyclonal antibody also significantly reduced PMN numbers and pathology. Collectively, evidence is provided that MIP-1alpha directly contributed to CD4+ T cell recruitment and indirectly to PMN persistence in the infected cornea.

  19. Antimicrobial Resistance Patterns of Acinetobacter baumannii, Pseudomonas aeruginosa and Staphylococcus aureus Isolated From Patients With Nosocomial Infections Admitted to Tehran Hospitals

    Directory of Open Access Journals (Sweden)

    Fallah

    1970-01-01

    Full Text Available Background Nosocomial infections constitute a global health problem, leading to a high rate of morbidity and mortality. The choice of antimicrobial treatment for nosocomial infections is often empirical and based on the knowledge of local antimicrobial activity patterns of the most common bacteria causing such infections. Objectives The aim of this study was to determine the 3 most prevalent bacterial pathogens including Acinetobacter baumannii, Pseudomonas aeruginosa and Staphylococcus aureus causing nosocomial infections and their antimicrobial resistant profiles in patients admitted to three hospitals in Tehran city, Iran. Materials and Methods In this cross-sectional study, the A. baumannii, P. aeruginosa and S. aureus isolates were obtained from different samples of patients with nosocomial infections admitted to different wards of three hospitals including Milad, Motahary and Loghman from November 2014 to April 2015. Nosocomial infections were defined as a culture-proven infection, which occurred more than 48 hours after admission. Antimicrobial susceptibility testing was performed using the disk diffusion method according to Clinical and Laboratory Standards Institute (CLSI guidelines. Results In total, 539 samples were collected during the study period from patients with nosocomial infections. Overall, 198, 75 and 98 A. baumannii, P. aeruginosa and S. aureus isolates were obtained, respectively. Cefepim and meropenem were found to be the most effective antibiotics for nosocomial infections caused by S. aureus with only 1 resistant isolate. Resistance to gentamicin and amikacin and susceptibility to cefepim was the highest compared to other antibiotics amongst P. aeruginosa isolates which is in consistent with the fact that cephalosporins remain useful agents for the management of nosocomial infections caused by P. aeruginosa. Acinetobacter baumannii isolates showed lower susceptibility rates to imipenem and ciprofloxacin than other

  20. Organ-Specific Blood Signatures for Host Response to Infections

    Science.gov (United States)

    2012-04-03

    Pseudomonas aeruginosa PAK, Legionella pneumophila Philadelphia-1, and H1N1 Influenza virus (2009 pandemic Mex09, seasonal NIH50) (Task 1). The biothreat...and Legionella pneumophila experiments were performed with a deposition of ~1 x 106 CFU/lung. Infections with these non-biothreat lung pathogens...Influenza virus), as well as non-biothreat agents ( Legionella pneumophila , Pseudomonas aeruginosa,). Through collaborative efforts with researchers at

  1. Development of antibiotic resistance in Pseudomonas aeruginosa during two decades of antipseudomonal treatment at the Danish CF Center

    DEFF Research Database (Denmark)

    Ciofu, O; Giwercman, B; Pedersen, S S

    1994-01-01

    was found between the MIC and the number of antipseudomonal courses of antibiotics. The proportion of resistant in vivo selected P. aeruginosa strains, presumed to be stably derepressed producers of chromosomal beta-lactamase, also increased significantly during the period studied. Our results confirm...... that the beta-lactamase production is an important mechanism of antibiotic resistance in P. aeruginosa.......At the Danish CF Center patients with chronic Pseudomonas aeruginosa lung infection were treated 3-4 times a year (from 1976) with a 2-week intravenous antipseudomonal course which included preferentially an aminoglycoside and a beta-lactam antibiotic. We investigated the development of antibiotic...

  2. Chlamydia pneumoniae infection in mice induces chronic lung inflammation, iBALT formation, and fibrosis.

    Directory of Open Access Journals (Sweden)

    Madhulika Jupelli

    Full Text Available Chlamydia pneumoniae (CP lung infection can induce chronic lung inflammation and is associated with not only acute asthma but also COPD exacerbations. However, in mouse models of CP infection, most studies have investigated specifically the acute phase of the infection and not the longer-term chronic changes in the lungs. We infected C57BL/6 mice with 5 × 10(5 CP intratracheally and monitored inflammation, cellular infiltrates and cytokine levels over time to investigate the chronic inflammatory lung changes. While bacteria numbers declined by day 28, macrophage numbers remained high through day 35. Immune cell clusters were detected as early as day 14 and persisted through day 35, and stained positive for B, T, and follicular dendritic cells, indicating these clusters were inducible bronchus associated lymphoid tissues (iBALTs. Classically activated inflammatory M1 macrophages were the predominant subtype early on while alternatively activated M2 macrophages increased later during infection. Adoptive transfer of M1 but not M2 macrophages intratracheally 1 week after infection resulted in greater lung inflammation, severe fibrosis, and increased numbers of iBALTS 35 days after infection. In summary, we show that CP lung infection in mice induces chronic inflammatory changes including iBALT formations as well as fibrosis. These observations suggest that the M1 macrophages, which are part of the normal response to clear acute C. pneumoniae lung infection, result in an enhanced acute response when present in excess numbers, with greater inflammation, tissue injury, and severe fibrosis.

  3. IL-22 is essential for lung epithelial repair following influenza infection.

    Science.gov (United States)

    Pociask, Derek A; Scheller, Erich V; Mandalapu, Sivanarayana; McHugh, Kevin J; Enelow, Richard I; Fattman, Cheryl L; Kolls, Jay K; Alcorn, John F

    2013-04-01

    Influenza infection is widespread in the United States and the world. Despite low mortality rates due to infection, morbidity is common and little is known about the molecular events involved in recovery. Influenza infection results in persistent distal lung remodeling, and the mechanism(s) involved are poorly understood. Recently IL-22 has been found to mediate epithelial repair. We propose that IL-22 is critical for recovery of normal lung function and architecture after influenza infection. Wild-type and IL-22(-/-) mice were infected with influenza A PR8/34 H1N1 and were followed up for up to 21 days post infection. IL-22 receptor was localized to the airway epithelium in naive mice but was expressed at the sites of parenchymal lung remodeling induced by influenza infection. IL-22(-/-) mice displayed exacerbated lung injury compared with wild-type mice, which correlated with decreased lung function 21 days post infection. Epithelial metaplasia was observed in wild-type mice but was not evident in IL-22(-/-) animals that were characterized with an increased fibrotic phenotype. Gene expression analysis revealed aberrant expression of epithelial genes involved in repair processes, among changes in several other biological processes. These data indicate that IL-22 is required for normal lung repair after influenza infection. IL-22 represents a novel pathway involved in interstitial lung disease.

  4. Effects of ambroxol on alginate of mature Pseudomonas aeruginosa biofilms.

    Science.gov (United States)

    Li, Fang; Yu, Jialin; Yang, Hua; Wan, Zhenyan; Bai, Dan

    2008-07-01

    Biofilm-forming bacteria Pseudomonas aeruginosa is a common pathogen in mechanically ventilated newborns, which can cause life-threatening infections. Alginate of mucoid Pseudomonas aeruginosa biofilms is considered an important virulence factor which contributes to the resistance to antibiotics. Traditionally, ambroxol is widely used in newborns with lung problems as a mucolytic agent and antioxidant agent as well. And there are few studies that demonstrated the anti-biofilm activity of ambroxol. In this study, we found that ambroxol can affect the structure of mucoid Pseudomonas aeruginosa biofilms. Further, we found that ambroxol reduces the production of alginate, the expression of the important genes and the activity of key enzyme guanosine diphospho-D-mannose dehydrogenase (GDP-mannose dehydrogenase; GMD) which were involved in alginate biosynthesis.

  5. Pyoverdine, the Major Siderophore in Pseudomonas aeruginosa, Evades NGAL Recognition

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    Mary E. Peek

    2012-01-01

    Full Text Available Pseudomonas aeruginosa is the most common pathogen that persists in the cystic fibrosis lungs. Bacteria such as P. aeruginosa secrete siderophores (iron-chelating molecules and the host limits bacterial growth by producing neutrophil-gelatinase-associated lipocalin (NGAL that specifically scavenges bacterial siderophores, therefore preventing bacteria from establishing infection. P. aeruginosa produces a major siderophore known as pyoverdine, found to be important for bacterial virulence and biofilm development. We report that pyoverdine did not bind to NGAL, as measured by tryptophan fluorescence quenching, while enterobactin bound to NGAL effectively causing a strong response. The experimental data indicate that pyoverdine evades NGAL recognition. We then employed a molecular modeling approach to simulate the binding of pyoverdine to human NGAL using NGAL’s published crystal structures. The docking of pyoverdine to NGAL predicted nine different docking positions; however, neither apo- nor ferric forms of pyoverdine docked into the ligand-binding site in the calyx of NGAL where siderophores are known to bind. The molecular modeling results offer structural support that pyoverdine does not bind to NGAL, confirming the results obtained in the tryptophan quenching assay. The data suggest that pyoverdine is a stealth siderophore that evades NGAL recognition allowing P. aeruginosa to establish chronic infections in CF lungs.

  6. Evolution and adaptation in Pseudomonas aeruginosa biofilms driven by mismatch repair system-deficient mutators.

    Science.gov (United States)

    Luján, Adela M; Maciá, María D; Yang, Liang; Molin, Søren; Oliver, Antonio; Smania, Andrea M

    2011-01-01

    Pseudomonas aeruginosa is an important opportunistic pathogen causing chronic airway infections, especially in cystic fibrosis (CF) patients. The majority of the CF patients acquire P. aeruginosa during early childhood, and most of them develop chronic infections resulting in severe lung disease, which are rarely eradicated despite intensive antibiotic therapy. Current knowledge indicates that three major adaptive strategies, biofilm development, phenotypic diversification, and mutator phenotypes [driven by a defective mismatch repair system (MRS)], play important roles in P. aeruginosa chronic infections, but the relationship between these strategies is still poorly understood. We have used the flow-cell biofilm model system to investigate the impact of the mutS associated mutator phenotype on development, dynamics, diversification and adaptation of P. aeruginosa biofilms. Through competition experiments we demonstrate for the first time that P. aeruginosa MRS-deficient mutators had enhanced adaptability over wild-type strains when grown in structured biofilms but not as planktonic cells. This advantage was associated with enhanced micro-colony development and increased rates of phenotypic diversification, evidenced by biofilm architecture features and by a wider range and proportion of morphotypic colony variants, respectively. Additionally, morphotypic variants generated in mutator biofilms showed increased competitiveness, providing further evidence for mutator-driven adaptive evolution in the biofilm mode of growth. This work helps to understand the basis for the specific high proportion and role of mutators in chronic infections, where P. aeruginosa develops in biofilm communities.

  7. Evolution and adaptation in Pseudomonas aeruginosa biofilms driven by mismatch repair system-deficient mutators.

    Directory of Open Access Journals (Sweden)

    Adela M Luján

    Full Text Available Pseudomonas aeruginosa is an important opportunistic pathogen causing chronic airway infections, especially in cystic fibrosis (CF patients. The majority of the CF patients acquire P. aeruginosa during early childhood, and most of them develop chronic infections resulting in severe lung disease, which are rarely eradicated despite intensive antibiotic therapy. Current knowledge indicates that three major adaptive strategies, biofilm development, phenotypic diversification, and mutator phenotypes [driven by a defective mismatch repair system (MRS], play important roles in P. aeruginosa chronic infections, but the relationship between these strategies is still poorly understood. We have used the flow-cell biofilm model system to investigate the impact of the mutS associated mutator phenotype on development, dynamics, diversification and adaptation of P. aeruginosa biofilms. Through competition experiments we demonstrate for the first time that P. aeruginosa MRS-deficient mutators had enhanced adaptability over wild-type strains when grown in structured biofilms but not as planktonic cells. This advantage was associated with enhanced micro-colony development and increased rates of phenotypic diversification, evidenced by biofilm architecture features and by a wider range and proportion of morphotypic colony variants, respectively. Additionally, morphotypic variants generated in mutator biofilms showed increased competitiveness, providing further evidence for mutator-driven adaptive evolution in the biofilm mode of growth. This work helps to understand the basis for the specific high proportion and role of mutators in chronic infections, where P. aeruginosa develops in biofilm communities.

  8. Immunological evaluation of an alginate-based conjugate as a vaccine candidate against Pseudomonas aeruginosa.

    Science.gov (United States)

    Farjah, Ali; Owlia, Parviz; Siadat, Seyed Davar; Mousavi, Seyed Fazlollah; Ardestani, Mehdi Shafiee; Mohammadpour, Hashem Khorsand

    2015-02-01

    Pseudomonas aeruginosa is an opportunistic pathogen that causes serious infections, is usually resistant to antimicrobial agents, and is the leading cause of morbidity and premature mortality in patients with cystic fibrosis (CF). Mucoid strains of P. aeruginosa produce a virulence factor known as alginate. Developing a strategy to raise opsonic antibodies against alginate could be promising for the treatment of P. aeruginosa infection in CF patients. Conjugation of alginate to a carrier protein is a good method for increasing the immunogenicity of alginate. We conjugated alginate to the outer membrane vesicle (OMV) of Neisseria meningitidis serogroup B, which is a safe carrier protein, and evaluated its efficacy in mice. To evaluate the immune response, total IgG, IgG1, IgG2a, and IgG2b titers were analyzed. Immunization of mice with the alginate-OMV conjugate raised the levels of opsonic antibodies, and the vaccinated mice were protected when challenged intranasally with P. aeruginosa. Further studies showed that the conjugated vaccine could eliminate P. aeruginosa from the lungs of infected mice. This study supports the proposal that immunization of mice with an alginate-OMV conjugate vaccine could be safe and protective against P. aeruginosa infection.

  9. Brote por Pseudomonas aeruginosa, en el área de atención ambulatoria de heridas quirúrgicas, en pacientes posmastectomizadas Outbreak of postmastectomy wound infections caused by Pseudomonas aeruginosa in an ambulatory surgical care setting

    Directory of Open Access Journals (Sweden)

    Diana Vilar-Compte

    2003-10-01

    Full Text Available OBJETIVO: Describir un brote por Pseudomonas aeruginosa, en el área de atención ambulatoria de herida quirúrgica, en pacientes posmastectomizadas. MATERIAL Y MÉTODOS: Entre el 13 de marzo y el 18 de mayo de 2000 se definió como caso a las pacientes del Instituto Nacional de Cancerología de la Ciudad de México, mastectomizadas con infección quirúrgica por P aeruginosa resistente a ciprofloxacina y gentamicina. Se tomaron cultivos de los antisépticos, del material de curaciones, del agua y del personal de salud. Se efectuó un análisis de casos y controles. RESULTADOS: Se identificaron 13 infecciones tardías del sitio quirúrgico por P aeruginosa. La Pseudomona se aisló de las narinas de la enfermera y de las gasas que ella misma colocaba sobre la mesa de mayo, pero no de los paquetes de gasas cerrados del área de curaciones ambulatoria de tumores mamarios. El 14 de abril de 2000 se transfirió a la enfermera a otra área y se instauraron medidas estrictas para el control de infecciones. Después de esta fecha se diagnosticaron cuatro casos más. La radioterapia fue el único factor de riesgo asociado con la infección (RM=5.1, IC 95%=1.1-28.4. CONCLUSIONES: El brote probablemente estuvo causado en un inicio por una fuente común y se extendió por infección cruzada entre las pacientes. Las prácticas deficientes detectadas en el manejo de heridas y drenajes condujo a instaurar medidas preventivas específicas.OBJECTIVE: To describe an outbreak due to Pseudomonas aeruginosa in postmastectomy wounds. MATERIAL AND METHODS: Cases were patients with a surgical infection caused by P. aeruginosa resistant to ciprofloxacin and gentamycin seen between March 13, 2000 and May 18, 2000, at Instituto Nacional de Cancerologia in Mexico City. Specimens for culturing were taken from faucets, antiseptics, and tap water, as well as from healthcare workers. A case-control analysis was conducted. RESULTS: Thirteen late surgical infections were caused

  10. Effect of apple cider vinegar on the healing of experimentally–induced wounds infected with Pseudomonas aeruginosa

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    A. H. Alawi

    2008-01-01

    Full Text Available Standard wounds were made in the backs of 18 rabbits. The rabbits were then divided into 6 equal groups. Rabbits of group (1, constituted a control group and their wounds were treated with physiological saline solution. In group (2, the wounds were treated with Cefotaxime at a concentration of 500 mg. Wounds of the third, fourth, and fifth groups were treated with 5%, 3.75%, and 2.5% apple cider vinegar respectively. Wounds of the sixth groups of rabbits were treated with a combination of equal amounts of Cefotaxime and apple cider vinegar 3.75%. All of the wounds were infected with various isolates of Pseudomonas aeruginosa at the time of infected. Wound treatment was done each 48 hours until complete healing. Results of this study indicated that using apple cider vinegar 3.75% gave results similar to those obtained by using the antibiotic (same rates of bacterial reduction. However, using a combination of equal amounts of apple cider vinegar and the antibiotic lead to more rapid and more better healing than using each one of them alone.

  11. Burn wounds infected with Pseudomonas aeruginosa triggers weight loss in rats

    Directory of Open Access Journals (Sweden)

    Su Grace

    2005-09-01

    Full Text Available Abstract Background Despite dramatic improvements in the management of burns, infection still remains a serious risk for the burn patient. The aim of this study was to shed light on the impact of acute burn injury with or without infection on cytokine profiles. Methods Sprague-Dawley rats (n = 21 were randomized into three groups: 1 burn only 2 burn and infection or 3 sham burn. Weight was monitored and blood was collected for cytokine ELISA, LPS quantification, and peripheral blood analysis. Animals were sacrificed either after 6 or 12 days. Results Infected animals showed substantial weight loss until day 6 post-burn as compared to burn alone. Endotoxin and TNF-α levels were elevated early in the infected burn group within 48 hours post-burn. In contrast, significant up-regulation of the anti-inflammatory cytokine IL-10 occurred later in the clinical course and was associated with the recovery from weight loss. Conclusion Our results suggest that in the presence of infection, you get a SIRS response possibly due to transient endotoxemia that is only seen in the infection group. In contrast, both burn and infection get a late IL-10 (CARS response, which is then associated with a return to normal weight in the infection group.

  12. In vitro efficacy of copper and silver ions in eradicating Pseudomonas aeruginosa, Stenotrophomonas maltophilia and Acinetobacter baumannii: implications for on-site disinfection for hospital infection control.

    Science.gov (United States)

    Huang, Hsin-I; Shih, Hsiu-Yun; Lee, Chien-Ming; Yang, Thomas C; Lay, Jiunn-Jyi; Lin, Yusen E

    2008-01-01

    Pseudomonas aeruginosa, Stenotrophomonas maltophilia and Acinetobacter baumannii are major opportunistic waterborne pathogens causing hospital-acquired infections. Copper-silver ionization has been shown to be effective in controlling Legionella colonization in hospital water systems. The objective was to determine the efficacy of copper and silver ions alone and in combination in eradicating P. aeruginosa, S. maltophilia and A. baumannii at the concentration applied to Legionella control. Kill curve experiments and mathematical modeling were conducted at copper and silver ion concentrations of 0.1, 0.2, 0.4, 0.8 and 0.01, 0.02, 0.04, 0.08 mg/L, respectively. The combinations of copper and silver ions were tested at concentrations of 0.2/0.02 and 0.4/0.04 mg/L, respectively. Initial organism concentration was ca. of 3 x 10(6)cfu/mL, and viability of the test organisms was assessed at predetermined time intervals. Samples (0.1 mL) withdrawn were mixed with 10 microL neutralizer solution immediately, serially diluted and plated in duplicate onto blood agar plates. The culture plates were incubated for 48 h at 37 degrees C and enumerated for the cfu (detection limit 10 cfu/mL). The results showed all copper ion concentrations tested (0.1-0.8 mg/L) achieved more than 99.999% reduction of P. aeruginosa which appears to be more susceptible to copper ions than S. maltophilia and A. baumannii. Silver ions concentration of 0.08 mg/L achieved more than 99.999% reduction of P. aeruginosa, S. maltophilia and A. baumannii in 6, 12 and 96 h, respectively. Combination of copper and silver ions exhibited a synergistic effect against P. aeruginosa and A. baumannii while the combination exhibited an antagonistic effect against S. maltophilia. Ionization may have a potential to eradicate P. aeruginosa, S. maltophilia and A. baumannii from hospital water systems.

  13. Influenza Virus Infection Induces Platelet-Endothelial Adhesion Which Contributes to Lung Injury.

    Science.gov (United States)

    Sugiyama, Michael G; Gamage, Asela; Zyla, Roman; Armstrong, Susan M; Advani, Suzanne; Advani, Andrew; Wang, Changsen; Lee, Warren L

    2015-12-04

    Lung injury after influenza infection is characterized by increased permeability of the lung microvasculature, culminating in acute respiratory failure. Platelets interact with activated endothelial cells and have been implicated in the pathogenesis of some forms of acute lung injury. Autopsy studies have revealed pulmonary microthrombi after influenza infection, and epidemiological studies suggest that influenza vaccination is protective against pulmonary thromboembolism; however, the effect of influenza infection on platelet-endothelial interactions is unclear. We demonstrate that endothelial infection with both laboratory and clinical strains of influenza virus increased the adhesion of human platelets to primary human lung microvascular endothelial cells. Platelets adhered to infected cells as well as to neighboring cells, suggesting a paracrine effect. Influenza infection caused the upregulation of von Willebrand factor and ICAM-1, but blocking these receptors did not prevent platelet-endothelial adhesion. Instead, platelet adhesion was inhibited by both RGDS peptide and a blocking antibody to platelet integrin α5β1, implicating endothelial fibronectin. Concordantly, lung histology from infected mice revealed viral dose-dependent colocalization of viral nucleoprotein and the endothelial marker PECAM-1, while platelet adhesion and fibronectin deposition also were observed in the lungs of influenza-infected mice. Inhibition of platelets using acetylsalicylic acid significantly improved survival, a finding confirmed using a second antiplatelet agent. Thus, influenza infection induces platelet-lung endothelial adhesion via fibronectin, contributing to mortality from acute lung injury. The inhibition of platelets may constitute a practical adjunctive strategy to the treatment of severe infections with influenza.IMPORTANCE There is growing appreciation of the involvement of the lung endothelium in the pathogenesis of severe infections with influenza virus. We have

  14. Clearance of Pseudomonas aeruginosa Foreign-Body Biofilm Infections through Reduction of the Cyclic Di-GMP Level in the Bacteria

    DEFF Research Database (Denmark)

    Christensen, Louise D.; van Gennip, Maria; Rybtke, Morten Theil

    2013-01-01

    Opportunistic pathogenic bacteria can engage in biofilm-based infections that evade immune responses and develop into chronic conditions. Because conventional antimicrobials cannot efficiently eradicate biofilms, there is an urgent need to develop alternative measures to combat biofilm infections....... It has recently been established that the secondary messenger cyclic diguanosine monophosphate (c-di-GMP) functions as a positive regulator of biofilm formation in several different bacteria. In the present study we investigated whether manipulation of the c-di-GMP level in bacteria potentially can...... of the majority of the bacteria in in vitro-grown P. aeruginosa biofilms. Subsequently, we demonstrated that P. aeruginosa biofilms growing on silicone implants, located in the peritoneal cavity of mice, dispersed after induction of the YhjH protein. Bacteria accumulated temporarily in the spleen after induction...

  15. Expression of Matrix Metalloproteinase-9 and -12 in Porcine Lung Infections

    DEFF Research Database (Denmark)

    Bruun, C. S.; Leifsson, P. S.; Johansen, L. K.

    2012-01-01

    Matrix metalloproteinases (MMPs) play a variety of roles during organogenesis, in the immune response and during acute and chronic diseases as well as in tissue remodelling. During the last decade, the pig has become used increasingly as a model for human diseases; however, studies on the express...... expressions were seen in the alveolar epithelium (MMP-9) and alveolar macrophages (MMP-12). These results are in accordance with studies of human lungs....... on the expression of porcine MMPs are limited. In the present study species-specific antibodies were produced to investigate the expression of MMP-9 and MMP-12 immunohistochemically in lungs from pigs infected with Actinobacillus pleuropneumoniae, Pasteurella multocida and Staphylococcus aureus. The immunolabelling...... of lung tissues (one infected and one control pig representing each infection) was evaluated for cellular distribution and intensity, which was scored semiquantitatively. When compared with healthy, non-infected controls, the expression of both MMP-9 and MMP-12 was higher in infected lungs. The highest...

  16. Complete Remission of Minimal Change Disease Following an Improvement of Lung Mycobacterium avium Infection.

    Science.gov (United States)

    Yamashiro, Aoi; Uchida, Takahiro; Ito, Seigo; Oshima, Naoki; Oda, Takashi; Kumagai, Hiroo

    A 46-year-old woman suddenly developed peripheral edema. Her massive proteinuria, hypoproteinemia, and renal biopsy findings yielded the diagnosis of minimal change disease (MCD). In addition, lung Mycobacterium avium infection was diagnosed according to a positive culture of her bronchoalveolar lavage fluid. The lung lesion was improved by anti-nontuberculous mycobacteria therapy. Surprisingly, her proteinuria also gradually decreased and she attained complete remission of MCD without any immunosuppressive therapy. She has subsequently remained in complete remission. We herein report an interesting case of MCD with lung Mycobacterium avium infection, suggesting a causal relationship among infection, immune system abnormality, and MCD/nephrotic syndrome.

  17. Risk assessment of Pseudomonas aeruginosa in water.

    Science.gov (United States)

    Mena, Kristina D; Gerba, Charles P

    2009-01-01

    P. aeruginosa is part of a large group of free-living bacteria that are ubiquitous in the environment. This organism is often found in natural waters such as lakes and rivers in concentrations of 10/100 mL to >1,000/100 mL. However, it is not often found in drinking water. Usually it is found in 2% of samples, or less, and at concentrations up to 2,300 mL(-1) (Allen and Geldreich 1975) or more often at 3-4 CFU/mL. Its occurrence in drinking water is probably related more to its ability to colonize biofilms in plumbing fixtures (i.e., faucets, showerheads, etc.) than its presence in the distribution system or treated drinking water. P. aeruginosa can survive in deionized or distilled water (van der Jooij et al. 1982; Warburton et al. 1994). Hence, it may be found in low nutrient or oligotrophic environments, as well as in high nutrient environments such as in sewage and in the human body. P. aeruginosa can cause a wide range of infections, and is a leading cause of illness in immunocompromised individuals. In particular, it can be a serious pathogen in hospitals (Dembry et al. 1998). It can cause endocarditis, osteomyelitis, pneumonia, urinary tract infections, gastrointestinal infections, and meningitis, and is a leading cause of septicemia. P. aeruginosa is also a major cause of folliculitis and ear infections acquired by exposure to recreational waters containing the bacterium. In addition, it has been recognized as a serious cause of keratitis, especially in patients wearing contact lenses. P. aeruginosa is also a major pathogen in burn and cystic fibrosis (CF) patients and causes a high mortality rate in both populations (MOlina et al. 1991; Pollack 1995). P. aeruginosa is frequently found in whirlpools and hot tubs, sometimes in 94-100% of those tested at concenrations of Price and Ahearn 1988). Many outbreaks of folliculitis and ear infections have been reportedly associated with the use of whirlpools and hot tubs that contain P. aeruginosa (Ratnam et al

  18. Evolutionary genomics of epidemic and nonepidemic strains of Pseudomonas aeruginosa.

    Science.gov (United States)

    Dettman, Jeremy R; Rodrigue, Nicolas; Aaron, Shawn D; Kassen, Rees

    2013-12-24

    Pseudomonas aeruginosa is an opportunistic pathogen of humans and is a major cause of morbidity and mortality in patients with cystic fibrosis (CF). Prolonged infection of the respiratory tract can lead to adaptation of the pathogen to the CF lung environment. To examine the general patterns of adaptation associated with chronic infection, we obtained genome sequences from a collection of P. aeruginosa isolated from airways of patients with CF. Our analyses support a nonclonal epidemic population structure, with a background of unique, recombining genotypes, and the rare occurrence of successful epidemic clones. We present unique genome sequence evidence for the intercontinental spread of an epidemic strain shared between CF clinics in the United Kingdom and North America. Analyses of core and accessory genomes identified candidate genes and important functional pathways associated with adaptive evolution. Many genes of interest were involved in biological functions with obvious roles in this pathosystem, such as biofilm formation, antibiotic metabolism, pathogenesis, transport, reduction/oxidation, and secretion. Key factors driving the adaptive evolution of this pathogen within the host appear to be the presence of oxidative stressors and antibiotics. Regions of the accessory genome unique to the epidemic strain were enriched for genes in transporter families that efflux heavy metals and antibiotics. The epidemic strain was significantly more resistant than nonepidemic strains to three different antibiotics. Multiple lines of evidence suggest that selection imposed by the CF lung environment has a major influence on genomic evolution and the genetic characteristics of P. aeruginosa isolates causing contemporary infection.

  19. Pharmacokinetics and pharmacodynamics of antibiotics in biofilm infections of Pseudomonas aeruginosa in vitro and in vivo

    DEFF Research Database (Denmark)

    Hengzhuang, Wang; Høiby, Niels; Ciofu, Oana

    2014-01-01

    an efficient dosing regimen and to minimize the development of antimicrobial tolerance and resistance in biofilm infections. Unfortunately, most previous PK/PD studies of antibiotics have been done on planktonic cells, and extrapolation of the results on biofilms is problematic as bacterial biofilms differ...... certificated for clinical use or proved useful for guidance of antibiotic therapy....

  20. RESPIRATORY VIRAL-INFECTIONS AGGRAVATE AIRWAY DAMAGE CAUSED BY CHRONIC REJECTION IN RAT LUNG ALLOGRAFTS

    NARCIS (Netherlands)

    WINTER, JB; GOUW, ASH; GROEN, M; WILDEVUUR, C; PROP, J

    1994-01-01

    Airway damage resulting in bronchiolitis obliterans occurs frequently in patients after heart-lung and lung transplantation. Generally, chronic rejection is assumed to be the most important cause of bronchiolitis obliterans. However, viral infections might also be potential causes of airway damage a

  1. Pharmacodynamics of Aerosolized Fosfomycin and Amikacin against Resistant Clinical Isolates of Pseudomonas aeruginosa and Klebsiella pneumoniae in a Hollow-Fiber Infection Model: Experimental Basis for Combination Therapy

    Science.gov (United States)

    Sime, Fekade Bruck; Johnson, Adam; Whalley, Sarah; Santoyo-Castelazo, Anahi; Montgomery, A. Bruce; Walters, Kathie Ann; Lipman, Jeffrey; Hope, William W.

    2016-01-01

    ABSTRACT There has been a resurgence of interest in aerosolization of antibiotics for treatment of patients with severe pneumonia caused by multidrug-resistant pathogens. A combination formulation of amikacin-fosfomycin is currently undergoing clinical testing although the exposure-response relationships of these drugs have not been fully characterized. The aim of this study was to describe the individual and combined antibacterial effects of simulated epithelial lining fluid exposures of aerosolized amikacin and fosfomycin against resistant clinical isolates of Pseudomonas aeruginosa (MICs of 16 mg/liter and 64 mg/liter) and Klebsiella pneumoniae (MICs of 2 mg/liter and 64 mg/liter) using a dynamic hollow-fiber infection model over 7 days. Targeted peak concentrations of 300 mg/liter amikacin and/or 1,200 mg/liter fosfomycin as a 12-hourly dosing regimens were used. Quantitative cultures were performed to describe changes in concentrations of the total and resistant bacterial populations. The targeted starting inoculum was 108 CFU/ml for both strains. We observed that neither amikacin nor fosfomycin monotherapy was bactericidal against P. aeruginosa while both were associated with rapid amplification of resistant P. aeruginosa strains (about 108 to 109 CFU/ml within 24 to 48 h). For K. pneumoniae, amikacin but not fosfomycin was bactericidal. When both drugs were combined, a rapid killing was observed for P. aeruginosa and K. pneumoniae (6-log kill within 24 h). Furthermore, the combination of amikacin and fosfomycin effectively suppressed growth of resistant strains of P. aeruginosa and K. pneumoniae. In conclusion, the combination of amikacin and fosfomycin was effective at maximizing bacterial killing and suppressing emergence of resistance against these clinical isolates. PMID:27795380

  2. Noncontact, Low Frequency Ultrasound as an Effective Therapy against Pseudomonas aeruginosa-infected Biofilm Wounds

    Science.gov (United States)

    2013-03-01

    effective. Previous studies have shown physical effects on cells and their surrounding matrix due to ultrasound energy, termed cavitation and...Noncontact, low-frequency ultrasound as an effective therapy against Pseudomonas aeruginosa–infected biofilm wounds Akhil K. Seth, MD1; Khang T...devices may potentially improve healing, but with no evidence of efficacy against biofilms. This study evaluates noncontact, low-frequency ultrasound

  3. Effect of infectious dose and season on development of hemorrhagic pneumonia in mink caused by Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Salomonsen, Charlotte Mark; Chriél, Mariann; Jensen, Trine Hammer

    2013-01-01

    Hemorrhagic pneumonia is an acute and fatal disease of farmed mink caused by Pseudomonas aeruginosa. The pathogenesis of this disease has not yet been resolved. Mink are the only animals known to be susceptible to acute, contagious, and fatal lung infections caused by P. aeruginosa. The purpose...... of this study was to investigate the correlation between dose-response and season of infection and to clarify whether Danish mink are carriers of P. aeruginosa on their nasal mucosa during the season for hemorrhagic pneumonia. To elucidate the pathogenesis of the disease, an infectious dose-response trial...... was carried out on adult mink and mink kits, both in the season for hemorrhagic pneumonia (November) as well as out of season (July). It proved difficult to infect mink via the intra-nasal route. Only 4 out of 60 infected mink developed clinical disease and were euthanized, all of them in November...

  4. Invasive Aspergillus infections in hospitalized patients with chronic lung disease

    Directory of Open Access Journals (Sweden)

    Wessolossky M

    2013-05-01

    Full Text Available Mireya Wessolossky,1 Verna L Welch,2 Ajanta Sen,1 Tara M Babu,1 David R Luke21Division of Infectious Diseases, University of Massachusetts Medical School, Worcester, MA, USA; 2Medical Affairs, Pfizer Inc, Collegeville, PA, USABackground: Although invasive pulmonary aspergillosis (IPA is more prevalent in immunocompromised patients, critical care clinicians need to be aware of the occurrence of IPA in the nontraditional host, such as a patient with chronic lung disease. The purpose of this study was to describe the IPA patient with chronic lung disease and compare the data with that of immunocompromised patients.Methods: The records of 351 patients with Aspergillus were evaluated in this single-center, retrospective study for evidence and outcomes of IPA. The outcomes of 57 patients with chronic lung disease and 56 immunocompromised patients were compared. Patients with chronic lung disease were defined by one of the following descriptive terms: emphysema, asthma, idiopathic lung disease, bronchitis, bronchiectasis, sarcoid, or pulmonary leukostasis.Results: Baseline demographics were similar between the two groups. Patients with chronic lung disease were primarily defined by emphysema (61% and asthma (18%, and immunocompromised patients primarily had malignancies (27% and bone marrow transplants (14%. A higher proportion of patients with chronic lung disease had a diagnosis of IPA by bronchoalveolar lavage versus the immunocompromised group (P < 0.03. The major risk factors for IPA were found to be steroid use in the chronic lung disease group and neutropenia and prior surgical procedures in the immunocompromised group. Overall, 53% and 69% of chronic lung disease and immunocompromised patients were cured (P = 0.14; 55% of chronic lung patients and 47% of immunocompromised patients survived one month (P = 0.75.Conclusion: Nontraditional patients with IPA, such as those with chronic lung disease, have outcomes and mortality similar to that in the

  5. The Effects of Berberine and Palmatine on Efflux Pumps Inhibition with Different Gene Patterns in Pseudomonas aeruginosa Isolated from Burn Infections

    Science.gov (United States)

    Aghayan, Seyed Sajjad; Kalalian Mogadam, Hamidreza; Fazli, Mozhgan; Darban-Sarokhalil, Davood; Khoramrooz, Seyed Sajjad; Jabalameli, Fereshteh; Yaslianifard, Somayeh; Mirzaii, Mehdi

    2017-01-01

    Background: Related Multidrug Resistance (MDR) to efflux pumps is a significant problem in treating infections caused by Pseudomonas aeruginosa (P. aeruginosa). Plant compounds have been identified as Pump Inhibitors (EPIs). In the current study, the potential effect of Berberine and Palmatine as EPIs were investigated on efflux pump inhibition through focusing on different gene patterns in P. aeruginosa isolated from burn infections. Methods: All isolates were collected and identified using the standard biochemical tests. Antimicrobial sensitivity was performed based on disk agar diffusion method for 12 antibiotics. MIC-MBC tests were also performed based on the broth microdilution method to detect synergistic relationship between ciprofloxacin, Berberine and Palmatine. Detection of mexA, mexB, mexC, mexD, mexE, mexF and mexX was conducted by PCR assay. Fisher’s Exact test and Logistic Regression were used as statistical tools. Results: A total of 60 P. aeruginosa isolates were collected. The highest and lowest levels of resistance were found to be respectively against clindamycin and tigecycline. Comparing the MIC with MBC distribution, it was found that Berberine and Palmatine lower the MIC-MBC level of ciprofloxacin. The PCR results indicated that the highest frequency is about MexAB-OprM operon. The statistical analysis among different gene patterns of efflux pumps showed that there were no significant relationships between the effectiveness of Berberine and Palmatine (p>0.05). Conclusion: It can be speculated that Berberine and Palmatine both act as EPIs and can be used as auxiliary treatments with the purpose of increasing the effect of available antibiotics as well as decreasing the emergence of MDR bacteria. The efficiency of these combinations should be studied further under in vivo conditions to have a more comprehensive conclusion regarding this issue. PMID:28090273

  6. LipL21 mRNA expression in lungs of hamsters infected with pathogenic Leptospira

    Institute of Scientific and Technical Information of China (English)

    Chintana Chirathaworn; Namo Suksomyos; Somchai Utivamek; Somboon Keelawat; Duangjai Suwancharoen; Duangporn Phulsuksombati; Yong Poovorawan

    2009-01-01

    Objective:Pulmonary haemorrhage is an increasing cause of death in leptospirosis patients.However,molecu-lar mechanism underlying pathologies in this organ is not clearly understood.It has been shown that sodium transport was disturbed following Leptospira infection.LipL21 is the second abundant outer membrane protein found only in pathogenic Leptospira.Its expression in vivo has been shown which suggests that this protein may be involved in survival in hosts or pathogenesis.However,the expression of this protein in host organs and its role in lung pathology has not been demonstrated.In this study we demonstrated the expression of LipL21 in lungs of hamsters infected with pathogenic Leptospira.Methods:Lung tissues were collected from Golden Syri-an hamsters injected with Leptospira interrogans serovar Pyrogenes at days 3,5 and 7 post-infection.Four ham-sters were used for each time point.Lungs from non-infected hamsters were collected as a control group.Li-pL21 mRNA expression in lung tissues was investigated by reverse transcription and nested PCR.Results:Li-pL21 mRNA expression was detected in all lung tissues from hamsters infected with pathogenic Leptospira.No PCR product was detected when tissues from non-infected hamsters were investigated.Conclusion:Our data demonstrated that LipL21 is expressed in lungs of hamsters infected with pathogenic Leptospira.Additional ex-periments such as quantitation and localization of LipL21 expression in lungs will provide further information whether this protein is involved in pathogenesis.

  7. The balance between protective and pathogenic immune responses in the TB-infected lung.

    Science.gov (United States)

    Orme, Ian M; Robinson, Richard T; Cooper, Andrea M

    2015-01-01

    Tuberculosis is a disease of the lung, and efficient transmission is dependent on the generation of a lesion in the lung, which results in a bacterium-laden cough. Mycobacterium tuberculosis (Mtb) is able to manipulate both the innate and acquired immune response of the host. This manipulation results in an effective CD4(+) T cell response that limits disease throughout the body but can also promote the development of progressively destructive lesions in the lung. In this way Mtb infection can result in an ambulatory individual who has a lesion in the lung capable of transmitting Mtb. The inflammatory environment within the lung lesion is manipulated by Mtb throughout infection and can limit the expression of acquired immunity by a variety of pathways.

  8. ExoU contributes to late killing of Pseudomonas aeruginosa - infected endothelial cells ExoU contribui para a morte tardia de células endoteliais infectadas por Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Alessandra Mattos Saliba

    2003-11-01

    Full Text Available To ascertain the role of ExoU in late P. aeruginosa cytotoxicity, endothelial cells (EC were exposed to wild type PA103, PA103deltaexoU and PA103::exsA for 1h and to gentamicin in culture medium. After 24h, the viability of PA103-infected cells (33.7 ± 14.3% was significantly lower than the viability of PA103deltaexoU- (77.7 ± 6.3% or PA103::exsA- (79.5 ± 23.3% infected EC. P. aeruginosa cytotoxicity did not depend on the bacterial ability to interact with EC because the percentage of cells with associated PA103 (35.9 ± 15.8% was similar to the percentage in PA103deltaexoU- (34.2 ± 16.0% and lower than the percentage in PA103::exsA-infected cultures (82.9 ± 18.9%. Cell treatment with cytochalasin D reduced the PA103 internalization by EC but did not interfere with its ability to kill host cells.Para determinar o papel de ExoU na citotoxicidade tardia de P. aeruginosa, células endoteliais (CE foram expostas às cepas PA103, PA103deltaxoU e PA103::exsA por 1h e à gentamicina em meio de cultura. Após 24h, a viabilidade das CE infectadas com PA103 (33.7 ± 14.3% foi inferior à de CE infectadas com PA103deltaexoU (77.7 ± 6.3% e PA103::exsA (79.5 ± 23.3%. A citotoxicidade não dependeu da capacidade de interagir com as CE porque o percentual de células com bactérias associadas em culturas expostas a PA103 foi semelhante ao percentual em culturas expostas a PA103deltaexoU e inferior em culturas expostas a PA103::exsA. O tratamento das CE com citocalasina D reduziu a internalização de PA103, mas não interferiu em sua citotoxicidade.

  9. Effect of infectious dose and season on development of hemorrhagic pneumonia in mink caused by Pseudomonas aeruginosa.

    Science.gov (United States)

    Salomonsen, Charlotte Mark; Chriél, Mariann; Jensen, Trine H; Rangstrup-Christensen, Lena; Høiby, Niels; Hammer, Anne Sofie

    2013-07-01

    Hemorrhagic pneumonia is an acute and fatal disease of farmed mink caused by Pseudomonas aeruginosa. The pathogenesis of this disease has not yet been resolved. Mink are the only animals known to be susceptible to acute, contagious, and fatal lung infections caused by P. aeruginosa. The purpose of this study was to investigate the correlation between dose-response and season of infection and to clarify whether Danish mink are carriers of P. aeruginosa on their nasal mucosa during the season for hemorrhagic pneumonia. To elucidate the pathogenesis of the disease, an infectious dose-response trial was carried out on adult mink and mink kits, both in the season for hemorrhagic pneumonia (November) as well as out of season (July). It proved difficult to infect mink via the intra-nasal route. Only 4 out of 60 infected mink developed clinical disease and were euthanized, all of them in November, illustrating that predisposing factors in the mink itself and not infectious dose might be crucial for disease development. We were able to culture P. aeruginosa from the nasal cavity of the clinically healthy experimental mink 8 d after inoculation. This indicated that the mink can carry P. aeruginosa on their nasal mucosa without developing the disease. It was not possible, however, to culture P. aeruginosa from the nasal cavity of clinically healthy mink obtained from farms in November, which indicates that the organism is not a normal part of the nasal mucosal flora of mink.

  10. Viral infection of human lung macrophages increases PDL1 expression via IFNβ.

    Directory of Open Access Journals (Sweden)

    Karl J Staples

    Full Text Available Lung macrophages are an important defence against respiratory viral infection and recent work has demonstrated that influenza-induced macrophage PDL1 expression in the murine lung leads to rapid modulation of CD8+ T cell responses via the PD1 receptor. This PD1/PDL1 pathway may downregulate acute inflammatory responses to prevent tissue damage. The aim of this study was to investigate the mechanisms of PDL1 regulation by human macrophages in response to viral infection. Ex-vivo viral infection models using influenza and RSV were established in human lung explants, isolated lung macrophages and monocyte-derived macrophages (MDM and analysed by flow cytometry and RT-PCR. Incubation of lung explants, lung macrophages and MDM with X31 resulted in mean cellular infection rates of 18%, 18% and 29% respectively. Viral infection significantly increased cell surface expression of PDL1 on explant macrophages, lung macrophages and MDM but not explant epithelial cells. Infected MDM induced IFNγ release from autologous CD8+ T cells, an effect enhanced by PDL1 blockade. We observed increases in PDL1 mRNA and IFNβ mRNA and protein release by MDM in response to influenza infection. Knockdown of IFNβ by siRNA, resulted in a 37.5% reduction in IFNβ gene expression in response to infection, and a significant decrease in PDL1 mRNA. Furthermore, when MDM were incubated with IFNβ, this cytokine caused increased expression of PDL1 mRNA. These data indicate that human macrophage PDL1 expression modulates CD8+ cell IFNγ release in response to virus and that this expression is regulated by autologous IFNβ production.

  11. Relationship between ceftolozane-tazobactam exposure and selection for Pseudomonas aeruginosa resistance in a hollow-fiber infection model.

    Science.gov (United States)

    VanScoy, Brian D; Mendes, Rodrigo E; Castanheira, Mariana; McCauley, Jennifer; Bhavnani, Sujata M; Jones, Ronald N; Friedrich, Lawrence V; Steenbergen, Judith N; Ambrose, Paul G

    2014-10-01

    It is important to understand the relationship between antibiotic exposure and the selection of drug resistance in the context of therapy exposure. We sought to identify the ceftolozane-tazobactam exposure necessary to prevent the amplification of drug-resistant bacterial subpopulations in a hollow-fiber infection model. Two Pseudomonas aeruginosa challenge isolates were selected for study, a wild-type ATCC strain (ceftolozane-tazobactam MIC, 0.5 mg/liter) and a clinical isolate (ceftolozane-tazobactam MIC, 4 mg/liter). The experiment duration was 10 days, and the ceftolozane-tazobactam dose ratio (2:1) and dosing interval (every 8 h) were selected to approximate those expected to be used clinically. The studied ceftolozane-tazobactam dosing regimens ranged from 62.5/31.25 to 2,000/1,000 mg per dose in step fold dilutions. Negative-control arms included no treatment and tazobactam at 500 mg every 8 h. Positive-control arms included ceftolozane at 1 g every 8 h and piperacillin-tazobactam dosed at 4.5 g every 6 h. For the wild-type ATCC strain, resistance was not selected by any ceftolozane-tazobactam regimen evaluated. For the clinical isolate, an inverted-U-shaped function best described the relationship between the amplification of a drug-resistant subpopulation and drug exposure. The least (62.5/31.25 mg) and most (2,000/1,000 mg) intensive ceftolozane-tazobactam dosing regimens did not select for drug resistance. Drug resistance selection was observed with intermediately intensive dosing regimens (125/62.5 through 1,000/500 mg). For the intermediately intensive ceftolozane-tazobactam dosing regimens, the duration until the selection for drug resistance increased with dose regimen intensity. These data support the selection of ceftolozane-tazobactam dosing regimens that minimize the potential for on-therapy drug resistance selection.

  12. Mixed Infection of Mycobacterium abscessus subsp. abscessus and Mycobacterium tuberculosis in the Lung

    Science.gov (United States)

    Sohn, Sungmin; Wang, Sungho; Shi, Hyejin; Park, Sungrock; Lee, Sangki; Park, Kyoung Taek

    2017-01-01

    A mixed infection of Mycobacterium abscessus subsp. abscessus (Mab) and Mycobacterium tuberculosis (MTB) in the lung is an unusual clinical manifestation and has not yet been reported. A 61-year-old woman had been treated for Mab lung disease and concomitant pneumonia, and was diagnosed with pulmonary tuberculosis (PTB). Despite both anti-PTB and anti-Mab therapy, her entire left lung was destroyed and collapsed. She underwent left pneumonectomy and received medical therapy. We were able to successfully treat her mixed infection by pneumonectomy followed by inhaled amikacin therapy. To the best of our knowledge, thus far, this is the first description of a mixed Mab and MTB lung infection. PMID:28180105

  13. Intestinal colonization with Enterococcus faecium does not influence pulmonary defense against Pseudomonas aeruginosa in mice.

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    Masja Leendertse

    Full Text Available BACKGROUND: Enterococci, and especially multiresistant Enterococcus faecium, are increasingly found colonizing hospitalized patients. This increased prevalence of colonization is not only associated with an increased prevalence of infections caused by enterococci, but also by infections with other nosocomial pathogens. In this study we investigated the causality of this observed relationship, by determining the influence of intestinal colonization with E. faecium on pulmonary defense against Pseudomonas aeruginosa. METHODOLOGY/PRINCIPAL FINDINGS: Three groups of mice were tested; 2 groups of mice were pre-treated with vancomycin, of which one group was subsequently treated by oral gavage of vancomycin-resistant E. faecium (VRE. The third group did not receive any pre-treatment. P. aeruginosa pneumonia was induced in all mice. Vancomycin treatment resulted in intestinal gram-negative bacterial overgrowth and VRE treatment resulted in colonization throughout the intestines. All 3 groups of mice were able to clear P. aeruginosa from the lungs and circulation, with comparable lung cytokine responses and lung damage. Mice treated with vancomycin without VRE colonization displayed modestly increased plasma levels of TNF-alpha and IL-10. CONCLUSION: Overgrowth of E. faecium and/or gram-negative bacteria does not impact importantly on pulmonary defense against P. aeruginosa pneumonia.

  14. A diagnostic PCR assay for the detection of an Australian epidemic strain of Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Murphy Anna

    2010-07-01

    Full Text Available Abstract Background Chronic lung infection with the bacterium Pseudomonas aeruginosa is one of the hallmarks of cystic fibrosis (CF and is associated with worsening lung function, increased hospitalisation and reduced life expectancy. A virulent clonal strain of P. aeruginosa (Australian epidemic strain I; AES-I has been found to be widespread in CF patients in eastern Australia. Methods Suppression subtractive hybridization (SSH was employed to identify genetic sequences that are present in the AES-I strain but absent from the sequenced reference strain PAO1. We used PCR to evaluate the distribution of several of the AES-I loci amongst a collection of 188 P. aeruginosa isolates which was comprised of 35 AES-I isolates (as determined by PFGE, 78 non-AES-I CF isolates including other epidemic CF strains as well as 69 P. aeruginosa isolates from other clinical and environmental sources. Results We have identified a unique AES-I genetic locus that is present in all 35 AES-I isolates tested and not present in any of the other 153 P. aeruginosa strains examined. We have used this unique AES-I locus to develop a diagnostic PCR and a real-time PCR assay to detect the presence of P. aeruginosa and AES-I in patient sputum samples. Conclusions We have developed diagnostic PCR assays that are 100% sensitive and 100% specific for the P. aeruginosa strain AES-I. We have also shown that Whatman FTA® Elute cards may be used with PCR-based assays to rapidly detect the presence of P. aeruginosa strains in CF sputum.

  15. First Report of Lung Transplantation in a Patient With Active Pulmonary Mycobacterium simiae Infection

    DEFF Research Database (Denmark)

    Qvist, T; Katzenstein, Terese Lea; Lillebaek, T

    2013-01-01

    Mycobacterium simiae is a slow-growing mycobacteria that in rare cases can cause chronic pulmonary infection. We report the first case of lung transplantation in a patient with active M simiae infection at the time of transplantation. A 56-year-old immunocompetent nonsmoking woman underwent...

  16. Protective anti-Pseudomonas aeruginosa humoral and cellular mucosal immunity by AdC7-mediated expression of the P. aeruginosa protein OprF.

    Science.gov (United States)

    Krause, Anja; Whu, Wen Zhu; Xu, Yaqin; Joh, Ju; Crystal, Ronald G; Worgall, Stefan

    2011-03-03

    Replication-deficient adenoviral (Ad) vectors are an attractive platform for a vaccine against lung infections caused by Pseudomonas aeruginosa. Ad vectors based on non-human serotypes have been developed to circumvent the problem of pre-existing anti-Ad immunity in humans. The present study analyzes the anti-P. aeruginosa systemic and lung mucosal immunity elicited by a non-human primate-based AdC7 vector expressing the outer membrane protein F (AdC7OprF) of P. aeruginosa. Intramuscular immunization of mice with AdC7OprF induced similar levels of serum and mucosal anti-OprF IgG and increased levels of anti-OprF IgA in lung epithelial lining fluid (ELF) compared to immunization with a human serotype Ad5OprF vector (p>0.05). OprF-specific INF-γ in splenic T cells stimulated with OprF-pulsed syngeneic splenic dendritic cells (DC) was similar following immunization with AdC7OprF compared to Ad5OprF (p>0.05). In contrast, OprF-specific INF-γ responses in lung T cells stimulated with either spleen or lung DC were increased following immunization with AdC7OprF compared to Ad5OprF (pmucosal immunity.

  17. Co-Carriage of blaKPC-2 and blaNDM-1 in Clinical Isolates of Pseudomonas aeruginosa Associated with Hospital Infections from India.

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    Deepjyoti Paul

    Full Text Available Global spread of KPC poses to be a serious threat complicating treatment options in hospital settings. The present study investigates the genetic environment of blaKPC-2 among clinical isolates of Pseudomonas aeruginosa from a tertiary referral hospital of India. The study isolates were collected from different wards and clinics of Silchar Medical College and Hospital, India, from 2012-2013. The presence of blaKPC was confirmed by genotypic characterization followed by sequencing. Cloning of the blaKPC-2 gene was performed and the genetic environment of this gene was characterized as well. Transferability of the resistance gene was determined by transformation assay and Southern hybridization. Additionally, restriction mapping was also carried out. Two isolates of P. aeruginosa were found to harbor blaKPC-2, were resistant towards aminoglycosides, quinolone and β-lactam-β-lactamase inhibitor combination. In both the isolates, the resistance determinant was associated with class 1 integron and horizontally transferable. Both the isolates were co-harboring blaNDM-1. The first detection of this integron mediated blaKPC-2 coexisting with blaNDM-1 in P. aeruginosa from India is worrisome, and further investigation is required to track the gene cassette mediated blaKPC-2 in terms of infection control and to prevent the spread of this gene in hospitals as well as in the community.

  18. Detection of Temporal Clusters of Healthcare-Associated Infections or Colonizations with Pseudomonas aeruginosa in Two Hospitals: Comparison of SaTScan and WHONET Software Packages.

    Science.gov (United States)

    Lefebvre, Annick; Bertrand, Xavier; Vanhems, Philippe; Lucet, Jean-Christophe; Chavanet, Pascal; Astruc, Karine; Thouverez, Michelle; Quantin, Catherine; Aho-Glélé, Ludwig Serge

    2015-01-01

    The identification of temporal clusters of healthcare-associated colonizations or infections is a challenge in infection control. WHONET software is available to achieve these objectives using laboratory databases of hospitals but it has never been compared with SaTScan regarding its detection performance. This study provided the opportunity to evaluate the performance of WHONET software in comparison with SaTScan software as a reference to detect clusters of Pseudomonas aeruginosa. A retrospective study was conducted in two French university hospitals. Cases of P. aeruginosa colonizations or infections occurring between 1st January 2005 and 30th April 2014 in the first hospital were analyzed overall and by medical ward/care unit. Poisson temporal and space-time permutation models were used. Analyses were repeated for the second hospital on data from 1st July 2007 to 31st December 2013 to validate WHONET software (in comparison with SaTScan) in another setting. During the study period, 3,946 isolates of P. aeruginosa were recovered from 2,996 patients in the first hospital. The incidence rate was 89.8 per 100,000 patient-days (95% CI [87.0; 92.6]). Several clusters were observed overall and at the unit level and some of these were detected whatever the method used. WHONET results were consistent with the analyses that took patient-days and temporal trends into account in both hospitals. Because it is more flexible and easier to use than SaTScan, WHONET software seems to be a useful tool for the prospective surveillance of hospital data although it does not take populations at risk into account.

  19. Identification of cyanophage Ma-LBP and infection of the cyanobacterium Microcystis aeruginosa from an Australian subtropical lake by the virus.

    Science.gov (United States)

    Tucker, Stephen; Pollard, Peter

    2005-02-01

    Viruses can control the structure of bacterial communities in aquatic environments. The aim of this project was to determine if cyanophages (viruses specific to cyanobacteria) could exert a controlling influence on the abundance of the potentially toxic cyanobacterium Microcystis aeruginosa (host). M. aeruginosa was isolated, cultured, and characterized from a subtropical monomictic lake-Lake Baroon, Sunshine Coast, Queensland, Australia. The viral communities in the lake were separated from cyanobacterial grazers by filtration and chloroform washing. The natural lake viral cocktail was incubated with the M. aeruginosa host growing under optimal light and nutrient conditions. The specific growth rate of the host was 0.023 h(-1); generation time, 30.2 h. Within 6 days, the host abundance decreased by 95%. The density of the cyanophage was positively correlated with the rate of M. aeruginosa cell lysis (r(2) = 0.95). The cyanophage replication time was 11.2 h, with an average burst size of 28 viral particles per host cell. However, in 3 weeks, the cultured host community recovered, possibly because the host developed resistance (immunity) to the cyanophage. The multiplicity of infection was determined to be 2,890 virus-like particles/cultured host cell, using an undiluted lake viral population. Transmission electron microscopy showed that two types of virus were likely controlling the host cyanobacterial abundance. Both viruses displayed T7-like morphology and belonged to the Podoviridiae group (short tails) of viruses that we called cyanophage Ma-LBP. In Lake Baroon, the number of the cyanophage Ma-LBP was 5.6 x 10(4) cyanophage x ml(-1), representing 0.23% of the natural viral population of 2.46 x 10(7) x ml(-1). Our results showed that this cyanophage could be a major natural control mechanism of M. aeruginosa abundance in aquatic ecosystems like Lake Baroon. Future studies of potentially toxic cyanobacterial blooms need to consider factors that influence

  20. A meta-analysis of the association between Chlamydia pneumoniae infection and lung cancer risk

    Directory of Open Access Journals (Sweden)

    X Hua-Feng

    2015-01-01

    Full Text Available Objective: The association between Chlamydia pneumoniae infection and lung cancer risk was not clear with small number of cases in each study. The aim of this meta-analysis was to evaluate the correlation between pneumonia infection and lung cancer risk by pooling the open published papers. Materials and Methods: We searched the electronic databases of Medline, EMBASE, Web of Science, and China National Knowledge Infrastructure databases for publications related to the association between pneumonia infection and lung cancer risk. Odds ratio (OR and its 95% confidence interval (95% CI was used to assess the correlation. The data were pooled by Stata11.0 software (Stata Corporation, College Station, TX, USA. Results: Thirteen publications, involving 2549 lung cancer patients and 2764 controls were included in this meta-analysis. The pooled results indicated that the C. pneumoniae infection significant increased the risk of lung cancer OR = 2.07 (95% CI: 1.43–2.99 by random effect model. And for serum IgG, 12 publications reported the IgG positive rate in lung cancer patients and relative healthy controls. The pooled OR was 2.22 (95% CI: 1.41–3.50 by using the random effects model which indicated that the IgG positive rate was significantly higher in lung cancer patients than that of healthy controls. The sensitivity analysis indicated the pooled OR was not sensitive to a single study. However, Begger's funnel plot and Egger's line regression analysis indicated significant publications bias for this meta-analysis. Conclusions: According to the present published data, C. pneumoniae infection may increase the risk of lung cancer. However, for its significant publications and heterogeneity among the included studies, the conclusion should be interpreted cautiously.

  1. Treatment of lung infection in patients with cystic fibrosis

    DEFF Research Database (Denmark)

    Döring, Gerd; Flume, Patrick; Heijerman, Harry

    2012-01-01

    therapy for the major pathogens in CF airways, including prophylaxis against infection, eradication of early infection, suppression of chronic infection, and the treatment of infective exacerbations. We outline measures to optimize maintenance treatment for infection in the light of novel antibiotic drug...... formulations. We discuss new developments in culture-independent microbiological diagnostic techniques and the use of tools for monitoring the success of antibiotic treatment courses. Finally, cost-effectiveness analyses for antibiotic treatment in CF patients are discussed....

  2. High beta-Lactamase Levels Change the Pharmacodynamics of beta-Lactam Antibiotics in Pseudomonas aeruginosa Biofilms

    DEFF Research Database (Denmark)

    Wang, Hengzhuang; Ciofu, Oana; Yang, Liang

    2013-01-01

    Resistance to beta-lactam antibiotics is a frequent problem in Pseudomonas aeruginosa lung infection of cystic fibrosis (CF) patients. This resistance is mainly due to the hyperproduction of chromosomally encoded beta-lactamase and biofilm formation. The purpose of this study was to investigate...... the role of beta-lactamase in the pharmacokinetics (PK) and pharmacodynamics (PD) of ceftazidime and imipenem on P. aeruginosa biofilms. P. aeruginosa PAO1 and its corresponding beta-lactamase-overproducing mutant, PA Delta DDh2Dh3, were used in this study. Biofilms of these two strains in flow chambers...... activity of ceftazidime was observed for beta-lactamase-overproducing biofilms of P. aeruginosa in all three models. Ceftazidime showed time-dependent killing on planktonic PAO1 and PA Delta DDh2Dh3. This difference is probably due to the special distribution and accumulation in the biofilm matrix of beta...

  3. Evolution of metabolic divergence in Pseudomonas aeruginosa during long-term infection facilitates a proto-cooperative interspecies interaction

    DEFF Research Database (Denmark)

    Frydenlund Michelsen, Charlotte; Khademi, Seyed Mohammad Hossein; Johansen, Helle Krogh;

    2016-01-01

    in polymicrobial human infections. However, we have previously shown that the interactions between these two bacterial species are strain dependent. Whereas P. aeruginosa PAO1, a commonly used laboratory strain, effectively suppressed S. aureus growth, we observed a commensal-like interaction between the human......1 and DK2-P2M24-2003, which comprised several virulence factors and signaling 4-hydroxy-2-alkylquinoline (HAQ) molecules. Strikingly, a further modulation of the HAQ profile was observed in DK2-P2M24-2003 during interaction with S. aureus, resulting in an area with thickened colony morphology...

  4. Nocardia farcinica lung infection in a patient with cystic fibrosis: a case report

    OpenAIRE

    2010-01-01

    Abstract Introduction Respiratory tract infections are the major causes of morbidity and mortality in patients with cystic fibrosis. Nocardia are rarely implicated in these infections and few reports of the involvement of this species are found in the literature. Case presentation We describe a case of lung infection followed by chronic colonization of trimethoprim and sulfamethoxazole resistant Nocardia farcinica in a patient with cystic fibrosis. The chronic colonization of this uncommon ba...

  5. Pseudomonas aeruginosa elastase provides an escape from phagocytosis by degrading the pulmonary surfactant protein-A.

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    Zhizhou Kuang

    Full Text Available Pseudomonas aeruginosa is an opportunistic pathogen that causes both acute pneumonitis in immunocompromised patients and chronic lung infections in individuals with cystic fibrosis and other bronchiectasis. Over 75% of clinical isolates of P. aeruginosa secrete elastase B (LasB, an elastolytic metalloproteinase that is encoded by the lasB gene. Previously, in vitro studies have demonstrated that LasB degrades a number of components in both the innate and adaptive immune systems. These include surfactant proteins, antibacterial peptides, cytokines, chemokines and immunoglobulins. However, the contribution of LasB to lung infection by P. aeruginosa and to inactivation of pulmonary innate immunity in vivo needs more clarification. In this study, we examined the mechanisms underlying enhanced clearance of the ΔlasB mutant in mouse lungs. The ΔlasB mutant was attenuated in virulence when compared to the wild-type strain PAO1 during lung infection in SP-A+/+ mice. However, the ΔlasB mutant was as virulent as PAO1 in the lungs of SP-A⁻/⁻ mice. Detailed analysis showed that the ΔlasB mutant was more susceptible to SP-A-mediated opsonization but not membrane permeabilization. In vitro and in vivo phagocytosis experiments revealed that SP-A augmented the phagocytosis of ΔlasB mutant bacteria more efficiently than the isogenic wild-type PAO1. The ΔlasB mutant was found to have a severely reduced ability to degrade SP-A, consequently making it unable to evade opsonization by the collectin during phagocytosis. These results suggest that P. aeruginosa LasB protects against SP-A-mediated opsonization by degrading the collectin.

  6. Comparison of UVB and UVC irradiation disinfection efficacies on Pseudomonas Aeruginosa (P. aeruginosa) biofilm

    Science.gov (United States)

    Argyraki, A.; Markvart, M.; Nielsen, Anne; Bjarnsholt, T.; Bjørndal, L.; Petersen, P. M.

    2016-04-01

    Disinfection routines are important in all clinical applications. The uprising problem of antibiotic resistance has driven major research efforts towards alternative disinfection approaches, involving light-based solutions. Pseudomonas aeruginosa (P. aeruginosa) is a common bacterium that can cause skin, soft tissue, lungs, kidney and urinary tract infections. Moreover, it can be found on and in medical equipment causing often cross infections in hospitals. The objective of this study was to test the efficiency, of two different light-based disinfection treatments, namely UVB and UVC irradiation, on P. aeruginosa biofilms at different growth stages. In our experiments a new type of UV light emitting diodes (LEDs) were used to deliver UV irradiation on the biofilms, in the UVB (296nm) and UVC (266nm) region. The killing rate was studied as a function of dose for 24h grown biofilms. The dose was ramped from 72J/m2 to 10000J/m2. It was shown that UVB irradiation was more effective than UVC irradiation in inactivating P. aeruginosa biofilms. No colony forming units (CFU) were observed for the UVB treated biofilms when the dose was 10000 J/m2 (CFU in control sample: 7.5 x 104). UVB irradiation at a dose of 20000J/m2 on mature biofilms (72h grown) resulted in a 3.9 log killing efficacy. The fact that the wavelength of 296nm exists in daylight and has such disinfection ability on biofilms gives new perspectives for applications within disinfection at hospitals.

  7. Serial histopathological examination of the lungs of mice infected with influenza A virus PR8 strain.

    Directory of Open Access Journals (Sweden)

    Masaya Fukushi

    Full Text Available Avian influenza H5N1 and pandemic (H1N1 2009 viruses are known to induce viral pneumonia and subsequent acute respiratory distress syndrome (ARDS with diffuse alveolar damage (DAD. The mortality rate of ARDS/DAD is extremely high, at approximately 60%, and no effective treatment for ARDS/DAD has been established. We examined serial pathological changes in the lungs of mice infected with influenza virus to determine the progress from viral pneumonia to ARDS/DAD. Mice were intranasally infected with influenza A/Puerto Rico/8/34 (PR8 virus, and their lungs were examined both macro- and micro-pathologically every 2 days. We also evaluated general condition, survival rate, body weight, viral loads in lung, and surfactant proteins in serum. As a result, all infected mice died within 9 days postinfection. At 2 days postinfection, inflammation in alveolar septa, i.e., interstitial pneumonia, was observed around bronchioles. From 4 to 6 days postinfection, interstitial pneumonia with alveolar collapse expanded throughout the lungs. From 6 to 9 days postinfection, DAD with severe alveolar collapse was observed in the lungs of all of dying and dead mice. In contrast, DAD was not observed in the live infected-mice from 2 to 6 days postinfection, despite their poor general condition. In addition, histopathological analysis was performed in mice infected with a dose of PR8 virus which was 50% of the lethal dose for mice in the 20-day observation period. DAD with alveolar collapse was observed in all dead mice. However, in the surviving mice, instead of DAD, glandular metaplasia was broadly observed in their lungs. The present study indicates that DAD with severe alveolar collapse is associated with death in this mouse infection model of influenza virus. Inhibition of the development of DAD with alveolar collapse may decrease the mortality rate in severe viral pneumonia caused by influenza virus infection.

  8. Chelation of Membrane-Bound Cations by Extracellular DNA Activates the Type VI Secretion System in Pseudomonas aeruginosa.

    Science.gov (United States)

    Wilton, Mike; Wong, Megan J Q; Tang, Le; Liang, Xiaoye; Moore, Richard; Parkins, Michael D; Lewenza, Shawn; Dong, Tao G

    2016-08-01

    Pseudomonas aeruginosa employs its type VI secretion system (T6SS) as a highly effective and tightly regulated weapon to deliver toxic molecules to target cells. T6SS-secreted proteins of P. aeruginosa can be detected in the sputum of cystic fibrosis (CF) patients, who typically present a chronic and polymicrobial lung infection. However, the mechanism of T6SS activation in the CF lung is not fully understood. Here we demonstrate that extracellular DNA (eDNA), abundant within the CF airways, stimulates the dynamics of the H1-T6SS cluster apparatus in Pseudomonas aeruginosa PAO1. Addition of Mg(2+) or DNase with eDNA abolished such activation, while treatment with EDTA mimicked the eDNA effect, suggesting that the eDNA-mediated effect is due to chelation of outer membrane-bound cations. DNA-activated H1-T6SS enables P. aeruginosa to nonselectively attack neighboring species regardless of whether or not it was provoked. Because of the importance of the T6SS in interspecies interactions and the prevalence of eDNA in the environments that P. aeruginosa inhabits, our report reveals an important adaptation strategy that likely contributes to the competitive fitness of P. aeruginosa in polymicrobial communities.

  9. Outbreak of Pseudomonas aeruginosa bacteraemia in a haematology department

    DEFF Research Database (Denmark)

    Rasmussen, Benjamin Schnack; Christensen, Nikolas; Sørensen, Jan;

    2015-01-01

    INTRODUCTION: Infection by Pseudomonas aeruginosa represents a major cause of morbidity and mortality among immunocompromised patients. In Denmark, an increase in P. aeruginosa isolates from blood cultures from a haematology department prompted a hygienic audit in 2007. METHODS: Blood cultures...

  10. Cedecea davisae’s Role in a Polymicrobial Lung Infection in a Cystic Fibrosis Patient

    Directory of Open Access Journals (Sweden)

    Thayer G. Ismaael

    2012-01-01

    Full Text Available Chronic airway colonization and infection are the hallmark of cystic fibrosis (CF. Staphylococcus aureus, Pseudomonas aeruginosa, and Burkholderia cepacia are well-documented bacterial culprits in this chronic suppurative airway disease. Advanced molecular diagnostics have uncovered a possible role of a larger group of microorganisms in CF. Cedecea is a member of the family Enterobacteriaceae and is an emerging pathogen. We present a case of a polymicrobial healthcare-associated pneumonia in a CF patient caused by Cedecea davisae, among other bacteria.

  11. Pseudomonas aeruginosa recognizes and responds aggressively to the presence of polymorphonuclear leukocytes

    DEFF Research Database (Denmark)

    Alhede, Morten; Bjarnsholt, T.; Jensen, P.O.;

    2009-01-01

    Polymorphonuclear neutrophilic leukocytes (PMNs) play a central role in innate immunity, where they dominate the response to infections, in particular in the cystic fibrosis lung. PMNs are phagocytic cells that produce a wide range of antimicrobial agents aimed at killing invading bacteria. Howev...... rhamnolipids surround the biofilm bacteria and on contact eliminate incoming PMNs. Our data strengthen the view that cross-kingdom communication plays a key role in P. aeruginosa recognition and evasion of the host defence....

  12. Flagellin of Pseudomonas aeruginosa induces transforming growth factor beta 1 expression in normal bronchial epithelial cells through mitogen activated protein kinase cascades

    Institute of Scientific and Technical Information of China (English)

    YANG Jing-jing; WANG Dan-dan; SUN Tie-ying

    2011-01-01

    Background Acute lung infection due to Pseudomonas aeruginosa (P. Aeruginosa) is a serious problem, especially in patients with structural lung conditions or immune compromised hosts, leading to an overwhelming threat with a high risk of morbidity and mortality. As an outcome of infection, fibrosis can be linked with chronic lung diseases. But some fibrotic manifestations, such as an irreversible decrease of lung function and fibrous bands seen on chest imaging, have been found after an acute infection with P. Aeruginosa. Fibrogenesis/remodeling resulting from acute lung infection by P.aeruginosa is rarely reported. This study was designed to explore the relation between fibrogenesis/remodeling and acute infection by P. Aeruginosa in vitro. We used flagellin protein from P. Aeruginosa, a key initiator of acute P.aeruginosa lung infection, to elucidate mechanisms by which acute lung infection with P. Aeruginosa can cause fibrogenesis/remodeling.Methods We studied the effect of flagellin from P. Aeruginosa (flagellin for short) on the transforming growth factor beta 1 (TGF-β1) and interleukin-8 (IL-8) expression, and the possible involvement of the signaling pathway, tumor necrosis factor receptor-associated factor 6 (TRAF6)/mitogen activated protein kinase (MAPK) pathway. Flagellin was purified from the P. Aeruginosa standard strain, PAO1. Normal bronchial epithelial cells BEAS-2B were challenged with different concentrations of flagellin, and cell viability assessment was performed by cell counting kit-8. BEAS-2B cells were incubated with flagellin with the specific MAPK inhibitors or TRAF6 siRNA. Cell lysates and the cultured supernatant were collected. The level of TGF-β1 and IL-8 were detected by enzyme-linked immunosorbant assay (ELISA). Western blotting was used to detect the protein levels of MAPK signal proteins p38, c-Jun NH2-terminal kinase (JNK) and extracellular regulated kinase (ERK).Results Expression of TGF-β1 in BEAS-2B cells was elevated by

  13. 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.

  14. 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.

  15. Current situation and treatment of nosocomial infections of Pseudomonas aeruginosa%院内铜绿假单胞菌感染:现状和诊治

    Institute of Scientific and Technical Information of China (English)

    陆国平; 马健

    2016-01-01

    院内铜绿假单胞菌感染是临床尤其是 ICU 的棘手问题,耐药率高,导致呼吸机相关性肺炎、血流感染等,治疗困难,延长住院时间,增加病死率和治疗成本。积极预防,早期明确、合理的抗生素治疗是铜绿假单胞菌治疗的关键。%Nosocomial infection of Pseudomonas aeruginosa is a dilemma in clinic,especially at ICU with high rate of antibiotic resistance,and lead to ventilator associated pneumonia,bloodstream infections, etc.There are difficulties in the treatment,lengthening of ICU stay,high mortality and increased treatment costs.Positive prevention,early diagnosis,reasonable antiboitics are the key to the benign prognosis of Pseud-omonas aeruginosa.

  16. Toward an Alternative Therapeutic Approach for Skin Infections: Antagonistic Activity of Lactobacilli Against Antibiotic-Resistant Staphylococcus aureus and Pseudomonas aeruginosa.

    Science.gov (United States)

    Hafez, Mohamed M; Maghrabi, Ibrahim A; Zaki, Noha M

    2013-09-01

    The wide spread of antimicrobial resistance has urged the need of alternative therapeutic approach. In this context, probiotic lactobacilli have been reported for the prevention and treatment of many gastrointestinal and urogenital infections. However, very little is known about their antagonistic activity against skin pathogens. Accordingly, the present study aimed to investigate the potential of lactobacilli to interfere with pathogenesis features of two antibiotic-resistant skin pathogens, namely methicillin-resistant Staphylococcus aureus and multiple-resistant Pseudomonas aeruginosa. A total of 49 lactobacilli were recovered, identified and tested for their antagonistic activities against the aforementioned pathogens. Of these, eight isolates were capable of blocking the adherence of pathogens to mammalian cells independent of the skin pathogen tested or model adopted. Moreover, three Lactobacillus isolates (LRA4, LC2 and LR5) effectively prevented the pathogen internalization into epithelial cells in addition to potentiating phagocyte-mediated pathogen killing. Interestingly, the lactobacilli LC2, LF9 and LRA4 markedly inhibited the growth of P. aeruginosa and S. aureus isolates in coculture experiments. Besides, the lactobacilli LRA4, LC2, LR5 and LF9 have counteracted pathogen cytotoxicity. Taken together, the present study revealed some inhibitory activities of lactobacilli against two antibiotic-resistant skin pathogens. Moreover, it revealed two lactobacilli, namely LC2 and LRA4, with antagonistic capacity against different virulence determinants of skin pathogens. These lactobacilli are considered promising probiotic candidates that may represent an alternative therapeutic approach for skin infections.

  17. Interspecific small molecule interactions between clinical isolates of Pseudomonas aeruginosa and Staphylococcus aureus from adult cystic fibrosis patients.

    Directory of Open Access Journals (Sweden)

    Alexandre Fugère

    Full Text Available Pseudomonas aeruginosa and Staphylococcus aureus are the most prevalent pathogens in airway infections of cystic fibrosis (CF patients. We studied how these pathogens coexist and interact with each other. Clinical isolates of both species were retrieved from adult CF patients. Culture supernatants from 63 P. aeruginosa isolates triggered a wide range of biofilm-stimulatory activities when added to the culture of a control S. aureus strain. The extent of biofilm formation by S. aureus was positively correlated to the levels of the 2-alkyl-4-(1H-quinolones (AQs Pseudomonas Quinolone Signal (PQS and 2-heptyl-4-hydroxy quinoline N-oxide (HQNO produced by the P. aeruginosa isolates. Supernatants from P. aeruginosa isogenic mutants deficient in PQS and HQNO production stimulated significantly less biofilm formation by S. aureus than that seen with the parental strain PA14. When studying co-isolated pairs of P. aeruginosa and S. aureus retrieved from patients showing both pathogens, P. aeruginosa supernatants stimulated less biofilm production by the S. aureus counterparts compared to that observed using the control S. aureus strain. Accordingly, some P. aeruginosa isolates produced low levels of exoproducts and also some of the clinical S. aureus isolates were not stimulated by their co-isolates or by PA14 despite adequate production of HQNO. This suggests that colonization of the CF lungs promotes some type of strain selection, or that co-existence requires specific adaptations by either or both pathogens. Results provide insights on bacterial interactions in CF.

  18. Pseudomonas quinolone signalling system: a component of quorum sensing cascade is a crucial player in the acute urinary tract infection caused by Pseudomonas aeruginosa.

    Science.gov (United States)

    Bala, Anju; Chhibber, Sanjay; Harjai, Kusum

    2014-11-01

    Pseudomonas aeruginosa is an opportunistic pathogen which employs quorum sensing system to regulate several genes required for its survival and pathogenicity within the host. Besides acylhomoserine lactone (AHL) mediated las and rhl systems, this organism possesses Pseudomonas quinolone signalling (PQS) system based on alkyl quinolone signal molecules. The quinolone system represents another layer of sophistication in the complex quorum sensing cascade. Therefore, in the present study, we evaluated the contribution of the PQS system in the establishment of acute urinary tract infection (UTI) in the mouse model. For this, wild-type parent strain of P. aeruginosa MPAO1 and its isogenic single transposon mutant strains pqsH and pqsA were employed to induce UTI in mice. PQS molecules in the tissue homogenates of mice were detected by high performance thin layer chromatography (HP-TLC) method. Virulence of strains was assessed in terms of bacteriological count, histopathological lesions in the renal and bladder tissue and generation of pathological index markers like reactive nitrogen intermediates and malondialdehyde. HP-TLC analysis showed presence of PQS molecules in the renal and bladder tissue of mice infected with MPAO1 while no PQS was detected in case of pqsH and pqsA mutant strains. Results indicated that MPAO1 possessing fully functional PQS biosynthetic genes was highly virulent and caused acute pyelonephritis with severe inflammation and tissue destruction. On the contrary, significant reduction in the log count, mild tissue damage and declined levels of pathological markers were observed in mice infected with mutant strains as compared to MPAO1. Further among mutants, all these parameters were maximally impaired in the pqsA mutant in which synthesis of alkyl quinolones was completely abolished due to the transposon mutation in respective gene. Virulence of the pqsH mutant strain was lesser than that of the MPAO1 but higher than pqsA mutant. In addition, the

  19. Contributions of efflux pumps to high level resistance of Pseudomonas aeruginosa to ciprofloxacin

    Institute of Scientific and Technical Information of China (English)

    WANG Dan-dan; SUN Tie-ying; HU Yun-jian

    2007-01-01

    @@ Pseudomonas aeruginosa (P. aeruginosa) is one of the leading pathogens involved in nosocomial pneumonia. In addition, P. aeruginosa infection is associated with significant morbidity and mortality.1 A major problem in P. aeruginosa infection is that this organism exhibits natural and acquired resistance to many structurally and functionally diverse antibiotics.

  20. Toxocariasis and lung function: relevance of a neglected infection in an urban landscape.

    Science.gov (United States)

    Walsh, Michael G; Haseeb, M A

    2014-03-01

    Toxocariasis has been highlighted as a potentially important neglected infection of poverty in developed countries that experience substantive health disparities such as the United States. An association between Toxocara infection and lung function, in concert with a relatively high prevalence of infection, may mark an important mechanism by which this infection could contribute significantly to the differential morbidity across different socioeconomic groups and landscapes. To assess the potential relevance of this infection in a dense urban environment, we measured the association between forced expiratory volume in 1 second (FEV₁) and serology diagnosed Toxocara infection in a sample of US-born New York City residents. We identified a significant independent association between Toxocara infection and lung function, wherein those with previous Toxocara infection had a 236.9 mL reduced FEV₁ compared to those without Toxocara infection even after adjusting for age, sex, ethnicity, level of education, smoking status, body mass index, and pet ownership. These findings from New York City corroborate similar findings in a national sample and, while the cross-sectional data preclude a direct causal relationship, this study identifies a potentially important neglected infection in a dense urban landscape.

  1. Proteolytic regulation of alginate overproduction in Pseudomonas aeruginosa.

    Science.gov (United States)

    Damron, F Heath; Goldberg, Joanna B

    2012-05-01

    Pseudomonas aeruginosa, a Gram-negative bacterium, is a significant opportunistic pathogen associated with skin and soft tissue infections, nosocomial pneumonia and sepsis. In addition, it can chronically colonize the lungs of cystic fibrosis (CF) patients. Overproduction of the exopolysaccharide called alginate provides P. aeruginosa with a selective advantage and facilitates survival in the CF lung. The in vitro phenotype of alginate overproduction observed on solid culture media is referred to as mucoid. Expression of the alginate machinery and biosynthetic enzymes are controlled by the extracytoplasmic sigma factor, σ(22) (AlgU/T). The key negative regulator of both σ(22) activity and the mucoid phenotype is the cognate anti-sigma factor MucA. MucA sequesters σ(22) to the inner membrane inhibiting the sigma factor's transcriptional activity. The well-studied mechanism for transition to the mucoid phenotype is mutation of mucA, leading to loss of MucA function and therefore activation of σ(22) . Recently, regulated intramembrane proteolysis (RIP) has been recognized as a mechanism whereby proteolysis of the anti-sigma factor MucA leads to active σ(22) allowing P. aeruginosa to respond to environmental stress conditions by overproduction of alginate. The goal of this review is to illuminate the pathways leading to RIP that have been identified and proposed.

  2. Anaerobic survival of Pseudomonas aeruginosa by pyruvate fermentation requires an Usp-type stress protein

    DEFF Research Database (Denmark)

    Schreiber, K; Boes, N; Escbach, M;

    2006-01-01

    Recently, we identified a pyruvate fermentation pathway in Pseudomonas aeruginosa sustaining anaerobic survival in the absence of alternative anaerobic respiratory and fermentative energy generation systems (M. Eschbach, K. Schreiber, K. Trunk, J. Buer, D. Jahn, and M. Schobert, J. Bacteriol. 186......:4596-4604, 2004). Anaerobic long-term survival of P. aeruginosa might be essential for survival in deeper layers of a biofilm and the persistent infection of anaerobic mucus plaques in the cystic fibrosis lung. Proteome analysis of P. aeruginosa cells during a 7-day period of pyruvate fermentation revealed...... the induced synthesis of three enzymes involved in arginine fermentation, ArcA, ArcB, and ArcC, and the outer membrane protein OprL. Moreover, formation of two proteins of unknown function, PA3309 and PA4352, increased by factors of 72- and 22-fold, respectively. Both belong to the group of universal stress...

  3. Infections with avian pathogenic and fecal Escherichia coli strains display similar lung histopathology and macrophage apoptosis.

    Directory of Open Access Journals (Sweden)

    Fabiana Horn

    Full Text Available The purpose of this study was to compare histopathological changes in the lungs of chickens infected with avian pathogenic (APEC and avian fecal (A(fecal Escherichia coli strains, and to analyze how the interaction of the bacteria with avian macrophages relates to the outcome of the infection. Chickens were infected intratracheally with three APEC strains, MT78, IMT5155, and UEL17, and one non-pathogenic A(fecal strain, IMT5104. The pathogenicity of the strains was assessed by isolating bacteria from lungs, kidneys, and spleens at 24 h post-infection (p.i.. Lungs were examined for histopathological changes at 12, 18, and 24 h p.i. Serial lung sections were stained with hematoxylin and eosin (HE, terminal deoxynucleotidyl dUTP nick end labeling (TUNEL for detection of apoptotic cells, and an anti-O2 antibody for detection of MT78 and IMT5155. UEL17 and IMT5104 did not cause systemic infections and the extents of lung colonization were two orders of magnitude lower than for the septicemic strains MT78 and IMT5155, yet all four strains caused the same extent of inflammation in the lungs. The inflammation was localized; there were some congested areas next to unaffected areas. Only the inflamed regions became labeled with anti-O2 antibody. TUNEL labeling revealed the presence of apoptotic cells at 12 h p.i in the inflamed regions only, and before any necrotic foci could be seen. The TUNEL-positive cells were very likely dying heterophils, as evidenced by the purulent inflammation. Some of the dying cells observed in avian lungs in situ may also be macrophages, since all four avian E. coli induced caspase 3/7 activation in monolayers of HD11 avian macrophages. In summary, both pathogenic and non-pathogenic fecal strains of avian E. coli produce focal infections in the avian lung, and these are accompanied by inflammation and cell death in the infected areas.

  4. A Pseudomonas aeruginosa toxin that hijacks the host ubiquitin proteolytic system.

    Directory of Open Access Journals (Sweden)

    Jennifer M Bomberger

    2011-03-01

    Full Text Available Pseudomonas aeruginosa (P. aeruginosa is an opportunistic pathogen chronically infecting the lungs of patients with chronic obstructive pulmonary disease (COPD, pneumonia, cystic fibrosis (CF, and bronchiectasis. Cif (PA2934, a bacterial toxin secreted in outer membrane vesicles (OMV by P. aeruginosa, reduces CFTR-mediated chloride secretion by human airway epithelial cells, a key driving force for mucociliary clearance. The aim of this study was to investigate the mechanism whereby Cif reduces CFTR-mediated chloride secretion. Cif redirected endocytosed CFTR from recycling endosomes to lysosomes by stabilizing an inhibitory effect of G3BP1 on the deubiquitinating enzyme (DUB, USP10, thereby reducing USP10-mediated deubiquitination of CFTR and increasing the degradation of CFTR in lysosomes. This is the first example of a bacterial toxin that regulates the activity of a host DUB. These data suggest that the ability of P. aeruginosa to chronically infect the lungs of patients with COPD, pneumonia, CF, and bronchiectasis is due in part to the secretion of OMV containing Cif, which inhibits CFTR-mediated chloride secretion and thereby reduces the mucociliary clearance of pathogens.

  5. A Pseudomonas aeruginosa toxin that hijacks the host ubiquitin proteolytic system.

    Science.gov (United States)

    Bomberger, Jennifer M; Ye, Siying; Maceachran, Daniel P; Koeppen, Katja; Barnaby, Roxanna L; O'Toole, George A; Stanton, Bruce A

    2011-03-01

    Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen chronically infecting the lungs of patients with chronic obstructive pulmonary disease (COPD), pneumonia, cystic fibrosis (CF), and bronchiectasis. Cif (PA2934), a bacterial toxin secreted in outer membrane vesicles (OMV) by P. aeruginosa, reduces CFTR-mediated chloride secretion by human airway epithelial cells, a key driving force for mucociliary clearance. The aim of this study was to investigate the mechanism whereby Cif reduces CFTR-mediated chloride secretion. Cif redirected endocytosed CFTR from recycling endosomes to lysosomes by stabilizing an inhibitory effect of G3BP1 on the deubiquitinating enzyme (DUB), USP10, thereby reducing USP10-mediated deubiquitination of CFTR and increasing the degradation of CFTR in lysosomes. This is the first example of a bacterial toxin that regulates the activity of a host DUB. These data suggest that the ability of P. aeruginosa to chronically infect the lungs of patients with COPD, pneumonia, CF, and bronchiectasis is due in part to the secretion of OMV containing Cif, which inhibits CFTR-mediated chloride secretion and thereby reduces the mucociliary clearance of pathogens.

  6. Chronic hepatitis E infection in lung transplant recipients

    NARCIS (Netherlands)

    Riezebos-Brilman, Annelies; Puchhammer-Stockl, Elisabeth; van der Weide, Hinke Y.; Haagsma, Elizabeth B.; Jaksch, Peter; Bejvl, Isabella; Niesters, Hubert G.; Verschuuren, Erik A. M.

    2013-01-01

    BACKGROUND: Hepatitis E virus (HEV) genotype 3 has been identified in patients with autochthonous HEV infections in developed countries and is currently being recognized as an emerging zoonotic pathogen. HEV infection may lead to a chronic hepatitis in immune-compromised patients. METHODS: We studie

  7. Lung function and bronchial responsiveness after Mycoplasma pneumoniae infection in early childhood

    DEFF Research Database (Denmark)

    Kjaer, B.B.; Jensen, J.S.; Nielsen, K.G.

    2008-01-01

    .17 versus 1.21 (kPa sec), P=0.45; and mean change in specific resistance was 13% versus 9%, P= 0.42. In conclusion, M. pneumoniae infection in early childhood was not associated with long-term effects on lung function and bronchial hyperresponsiveness 2 years after infection Udgivelsesdato: 2008/6......Mycoplasma (M.) pneumoniae has been associated with exacerbation of symptoms in asthmatic school children and adults; and an etiological role in asthma has been suggested. The purpose of this study was to investigate whether infection with M. pneumoniae in early childhood has a long-term influence...... on lung function and bronchial responsiveness. In a retrospective, clinical cohort-study children younger than 5 years-of-age when PCR-tested for M. pneumoniae were enrolled. Sixty-five children with clinical symptoms suggesting infection with M. pneumoniae during an epidemic season completed a clinical...

  8. 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....

  9. Proteomics of the oxidative stress response induced by hydrogen peroxide and paraquat reveals a novel AhpC-like protein in Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Hare, Nathan J; Scott, Nichollas E; Shin, Eun Hye H;

    2011-01-01

    . aeruginosa establishes infection in the cystic fibrosis lung and eventually out-competes other pathogenic bacteria to persist into chronic infection. We utilized a proteomics approach to identify the proteins associated with the oxidative stress response of P. aeruginosa PAO1 to hydrogen peroxide...... by hypothetical protein PA3529 following treatment with 10 mM H(2) O(2) . AhpC belongs to the 2-Cys peroxiredoxin family and is a redox enzyme responsible for removing peroxides in bacterial cells. MS analysis showed that PA3529 was altered by the formation of a dimer via a disulfide bond in a manner analogous...

  10. Immunization with 3-oxododecanoyl-L-homoserine lactone-r-PcrV conjugate enhances survival of mice against lethal burn infections caused by Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Isar Dejban Golpasha

    2015-05-01

    Full Text Available Quorum Sensing and type III secretion system play an important role in the virulence of Pseudomonas (P. aeruginosa in burn wound infections. We aimed to explore the feasibility of using 3-oxo-C12-HSL-r-PcrV conjugate as a candidate vaccine against P. aeruginosa caused infections. 3-oxo-C12-HSL-r-PcrV conjugate was prepared and used for immunization of mice (10 μg, subcutaneous, three times, at 2-week intervals. Mice were divided into five groups: I: PcrV; II: 3-oxo-C12-HSL-r-PcrV (10 μg; III: 3-oxo-C12-HSL-r-PcrV (20 μg; IV: 3-oxo-C12-HSL; and V: PBS receiving groups.  After each shot of immunization, total and isotype antibody responses against corresponding antigen were measured to determine the immunization efficacy. One month after the last immunization, all groups were burned and challenged subeschar with P. aeruginosa PAO1. Survival rate and bacterial quantity in the skin and internal organs (liver and spleen were evaluated 25-hr after burn infection. Immunization with 3-oxo-C12-HSL-r-PcrV significantly increased total IgG and specific subclass antibodies (IgG1, IgG2a, IgG2b, and IgM in the serum of the groups II and III compared to the control group (p<0.001. While all the control mice (PBS injected group died within 2 days after bacterial challenge, 64% of the group I, 78% of group II, and 86% of group III, survived within 14 days after challenge. Interestingly, bacterial burden in the liver and spleen of 3-oxo-C12-HSL-r-PcrV injected group (III was significantly lower than the control group (p<0.001.  The present study proposed two-component vaccine to inhibit Pseudomonas infections in burned mouse. 

  11. Experimental Pseudomonas aeruginosa mediated rhino sinusitis in mink

    DEFF Research Database (Denmark)

    Kirkeby, S.; Hammer, A. S.; Høiby, N.

    2017-01-01

    The nasal and sinus cavities in children may serve as reservoirs for microorganisms that cause recurrent and chronic lung infections. This study evaluates whether the mink can be used as an animal model for studying Pseudomonas aeruginosa mediated rhino-sinusitis since there is no suitable...... traditional animal model for this disease. Nasal tissue samples from infected and control mink were fixed in formalin, demineralized, and embedded in paraffin. A histological examination of sections from the infected animals revealed disintegration of the respiratory epithelium lining the nasal turbinates...... and swelling and edema of the submucosa. The expression of mucins and sialylated glycans was examined using immunohistochemistry. MUC1, MUC2 and MUC5AC were upregulated in the inoculated animals as a much stronger staining was present in the respiratory epithelium in the infected animals compared...

  12. Molecular detection of an atypical, highly resistant, clonal Pseudomonas aeruginosa isolate in cystic fibrosis patients.

    LENUS (Irish Health Repository)

    Keating, Deirdre

    2013-03-01

    The identification of Pseudomonas aeruginosa (P. aeruginosa) isolates in sputum from cystic fibrosis (CF) patients can be challenging due to the multitude of phenotypic changes isolates undergo during adaptation to the microenvironment of the CF lung.

  13. 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.

  14. Choriodecidual infection downregulates angiogenesis and morphogenesis pathways in fetal lungs from Macaca nemestrina.

    Directory of Open Access Journals (Sweden)

    Ryan M McAdams

    Full Text Available BACKGROUND: Intrauterine exposure to amniotic fluid (AF cytokines is thought to predispose to bronchopulmonary dysplasia (BPD. We evaluated the effects of GBS exposure on RNA expression in fetal lung tissue to determine early molecular pathways associated with fetal lung injury that may progress to BPD. METHODS: Ten chronically catheterized pregnant monkeys (Macaca nemestrina at 118-125 days gestation (term = 172 days received choriodecidual inoculation of either: 1 Group B Streptococcus (n = 5 or 2 saline (n = 5. Cesarean section and fetal necropsy was performed in the first week after GBS or saline inoculation regardless of labor. RNA was extracted from fetal lungs and profiled by microarray. Results were analyzed using single gene, Gene Set, and Ingenuity Pathway Analysis. Validation was by RT-PCR and immunohistochemistry. RESULTS: Despite uterine quiescence in most cases, fetal lung injury occurred in four GBS cases (intra-alveolar neutrophils, interstitial thickening and one control (peri-mortem hemorrhage. Significant elevations of AF cytokines (TNF-α, IL-8, IL-1β, IL-6 were detected in GBS versus controls (p<0.05. Lung injury was not directly caused by GBS, because GBS was undetectable by culture and PCR in the AF and fetal lungs. A total of 335 genes were differentially expressed greater than 1.5 fold (p<0.05 with GBS exposure associated with a striking upregulation of genes in innate and adaptive immunity and downregulation of pathways for angiogenesis, morphogenesis, and cellular growth and development. CONCLUSIONS: A transient choriodecidual infection may induce fetal lung injury with profound alterations in the genetic program of the fetal lung before signs of preterm labor. Our results provide a window for the first time into early molecular pathways disrupting fetal lung angiogenesis and morphogenesis before preterm labor occurs, which may set the stage for BPD. A strategy to prevent BPD should target the fetus in

  15. [Acanthamoeba, naturally intracellularly infected with Pseudomonas aeruginosa, after their isolation from a microbiologically contaminated drinking water system in a hospital].

    Science.gov (United States)

    Michel, R; Burghardt, H; Bergmann, H

    1995-03-01

    The drinking water system of a new hospital building that was highly contaminated with bacteria before opening was investigated too for the prevalence of small free living amoebae. Germ counts resulted in > 100 CFU/ml in 100% of the cold water samples, that showed also growth of P. aeruginosa, whereas E. coli and coliforme bacteria could not be identified. The investigation of 37 water samples for protozoa revealed growth of small freeliving amoebae in 20 samples (54%) belonging to 10 species of the genus Acanthamoeba, Naegleria, Hartmannella, Echinamoeba among others. In addition 2 Ciliate- and 2 Microflagellate-species could be observed. While all Naegleria strains isolated belonged to the N. gruberi-complex two of 16 Acanthamoeba-isolates proved to be pathogenic for laboratory mice. From 7 watersamples positive with P. aeruginosa 5 Acanthamoeba- and 2 Echinamoeba strains could be isolated which revealed intracellular multiplication of P. aeruginosa. Because of their well known resistances against chlorine, the amoebae and their cysts are considered to be vectors for these intracellular bacteria. A complete sanitation of the incriminated drinking water system was accomplished by combined chemical and thermic disinfection measures.

  16. Effects of Marijuana on the Lung and Its Defenses against Infection and Cancer.

    Science.gov (United States)

    Tashkin, Donald P.

    1999-01-01

    Examines the many effects of marijuana use on the lungs. States that patients with pre-existing immune deficits are particularly vulnerable to marijuana-related pulmonary infections. However, warns that habitual use of marijuana may lead to respiratory cancer must await epidemiological studies, which are now possible since 30 years have passed…

  17. Mechanical ventilation enhances lung inflammation and caspase activity in a model of mouse pneumovirus infection

    NARCIS (Netherlands)

    R.A. Bem; J.B.M. van Woensel; A.P. Bos; A. Koski; A.W. Farnand; J.B. Domachowske; H.F. Rosenberg; T.R. Martin; G. Matute-Bello

    2009-01-01

    Severe infection with respiratory syncytial virus (RSV) in children can progress to respiratory distress and acute lung injury (ALI). Accumulating evidence suggests that mechanical ventilation (MV) is an important cofactor in the development of ALI by modulating the host immune responses to bacteria

  18. TREM-2 promotes macrophage survival and lung disease after respiratory viral infection

    Science.gov (United States)

    Wu, Kangyun; Byers, Derek E.; Jin, Xiaohua; Agapov, Eugene; Alexander-Brett, Jennifer; Patel, Anand C.; Cella, Marina; Gilfilan, Susan; Colonna, Marco; Kober, Daniel L.; Brett, Tom J.

    2015-01-01

    Viral infections and type 2 immune responses are thought to be critical for the development of chronic respiratory disease, but the link between these events needs to be better defined. Here, we study a mouse model in which infection with a mouse parainfluenza virus known as Sendai virus (SeV) leads to long-term activation of innate immune cells that drive IL-13–dependent lung disease. We find that chronic postviral disease (signified by formation of excess airway mucus and accumulation of M2-differentiating lung macrophages) requires macrophage expression of triggering receptor expressed on myeloid cells-2 (TREM-2). Analysis of mechanism shows that viral replication increases lung macrophage levels of intracellular and cell surface TREM-2, and this action prevents macrophage apoptosis that would otherwise occur during the acute illness (5–12 d after inoculation). However, the largest increases in TREM-2 levels are found as the soluble form (sTREM-2) long after clearance of infection (49 d after inoculation). At this time, IL-13 and the adapter protein DAP12 promote TREM-2 cleavage to sTREM-2 that is unexpectedly active in preventing macrophage apoptosis. The results thereby define an unprecedented mechanism for a feed-forward expansion of lung macrophages (with IL-13 production and consequent M2 differentiation) that further explains how acute infection leads to chronic inflammatory disease. PMID:25897174

  19. Nonfermenting Gram-negative Bacilli other than Pseudomonas aeruginosa and Acinetobacter Spp. Causing Respiratory Tract Infections in a Tertiary Care Center

    Directory of Open Access Journals (Sweden)

    Kisumu Chawla

    2013-01-01

    Full Text Available Background: Nonfermenting gram-negative bacilli have emerged as important healthcare-associated pathogens. It is important to correctly identify all clinically significant nonfermenting gram-negative bacilli considering the intrinsic multidrug resistance exhibited by these bacteria. Materials and Methods: A retrospective study was undertaken to identify the various nonfermenting gram-negative bacilli other than Pseudomonas aeruginosa and Acinetobacter spp. isolated from respiratory samples (n = 9363, to understand their clinical relevance and to analyze their antibiotic susceptibility pattern. Results: Nonfermenting gram-negative bacilli were isolated from 830 (16.4% samples showing significant growth. Thirty-three (4% isolates constituted nonfermenting gram-negative bacilli other than P. aeruginosa and Acinetobacter spp. Stenotrophomonas maltophilia (15, 45.5% was the most common isolate followed by Burkholderia cepacia (4, 12.1%, Sphingomonas paucimobilis (3, 9.1%, and Achromobacter xylosoxidans (3, 9.1%. On the basis of clinicomicrobiological correlation, pathogenicity was observed in 69.7% (n = 23 isolates. Timely and correct treatment resulted in clinical improvement in 87.9% cases. Conclusion: Any nonfermenting gram-negative bacilli isolated from respiratory tract infection should not be ignored as mere contaminant, but correlated clinically for its pathogenic potential and identified using standard methods so as to institute appropriate and timely antibiotic coverage.

  20. Comparison between concentrations of amphotericin B in infected lung lesion and in uninfected lung tissue in a patient treated with liposomal amphotericin B (AmBisome).

    Science.gov (United States)

    Watanabe, Akira; Matsumoto, Kana; Igari, Hidetoshi; Uesato, Masaya; Yoshida, Shigetoshi; Nakamura, Yasutaka; Morita, Kunihiko; Shibuya, Kazutoshi; Matsubara, Hisahiro; Yoshino, Ichiro; Kamei, Katsuhiko

    2010-09-01

    Generally, the primary lesion of a mold infection is in the airway, an extravascular site. Therefore, the antifungal drug concentration at the actual tissue lesion of a mold infection is as important as in the blood compartment. Although our antifungal armamentarium has expanded recently, polyenes are still often needed in clinical practice because of their potent fungicidal activity and the rarity of resistance. Nevertheless, the distribution of amphotericin B (AmB) in infected lung tissue has not yet been evaluated. Using high-performance liquid chromatography analysis, we determined the concentrations of AmB in plasma and infected and uninfected tissues of resected lung simultaneously, in a patient with pulmonary aspergillosis treated with liposomal amphotericin B (L-AmB). The AmB concentration in the infected lesion of the lung was approximately 5.2 times higher than that in plasma and 3.7 times higher than in uninfected lung tissue. L-AmB accumulated in the infected lesion of the lung at a higher concentration. Although our data are from only one patient, they may be useful in helping to develop better strategies for the use of L-AmB against pulmonary fungal infections.

  1. Inhibition of lung serine proteases in mice: a potentially new approach to control influenza infection

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    Błazejewska Paulina

    2011-01-01

    Full Text Available Abstract Background Host serine proteases are essential for the influenza virus life cycle because the viral haemagglutinin is synthesized as a precursor which requires proteolytic maturation. Therefore, we studied the activity and expression of serine proteases in lungs from mice infected with influenza and evaluated the effect of serine protease inhibitors on virus replication both in cell culture and in infected mice. Results Two different inbred mouse strains were investigated: DBA/2J as a highly susceptible and C57Bl/6J as a more resistant strain to influenza virus infection. The serine proteases from lung homogenates of mice exhibited pH optima of 10.00. Using the substrate Bz-Val-Gly-Arg-p-nitroanilide or in zymograms, the intensities of proteolysis increased in homogenates from both mouse strains with time post infection (p.i. with the mouse-adapted influenza virus A/Puerto Rico/8/34 (H1N1; PR8. In zymograms at day 7 p.i., proteolytic bands were stronger and numerous in lung homogenates from DBA/2J than C57Bl/6J mice. Real-time PCR results confirmed differential expression of several lung proteases before and after infecting mice with the H1N1 virus. The most strongly up-regulated proteases were Gzma, Tmprss4, Elane, Ctrl, Gzmc and Gzmb. Pretreatment of mouse and human lung cell lines with the serine protease inhibitors AEBSF or pAB or a cocktail of both prior to infection with the H1N1 or the A/Seal/Massachusetts/1/80 (H7N7; SC35M virus resulted in a decrease in virus replication. Pretreatment of C57Bl/6J mice with either AEBSF or a cocktail of AEBSF and pAB prior to infection with the H1N1 virus significantly reduced weight loss and led to a faster recovery of treated versus untreated mice while pAB alone exerted a very poor effect. After infection with the H7N7 virus, the most significant reduction of weight loss was obtained upon pretreatment with either the protease inhibitor cocktail or pAB. Furthermore, pretreatment of C57BL/6J

  2. 铜绿假单胞菌血流感染27例临床分析%Clinical analysis of bloodstream infections caused by Pseudomonas aeruginosa

    Institute of Scientific and Technical Information of China (English)

    丁艳苓; 姚婉贞; 宁永忠

    2013-01-01

    Objective To analyze the clinical characteristics and antimicrobial resistance of blood stream infections caused by P. aeruginosa. Methods The clinical data were retrospectively reviewed for the patients with P. aeruginosa bloodstream infection who were treated in Peking University Third Hospital from January 2006 to December 2009. Results A total of 27 patients were found with P. aeruginosa bloodstream infection. The Charlson scores of the patients were 4. 48 ± 2. 10. All patients had fever and increased or decreased white blood cell counts when their bloodstream infection was identified. Six patients were infected by multidrug-resistant (MDR) strains. Compared with the patients with non-MDR P. aeruginosa infection, the patients infected by MDR strains had significantly higher APACHE TJ scores and Sequential Organ Failure Assessment (SOFA) scores at admission, longer stay in Intensive Care Unit (RICU and SICU), higher prevalence of multiple (two or more) antibiotics use before positive blood culture after admission, and lower proprotion of patients with appropriate antibiotic therapy after blood culture. The Charlson scores, clinical manifestation, APACHE TJ scores and SOFA scores at the time of bloodstream infection, and in-hospital mortality were similar between the two groups of patients. Conclusions The patients with P. aeruginosa bloodstream infection showed severe clinical status and high mortality rate. The MDR strains-infected patients had more severe conditions than those infected by non-MDR strains, but their clinical manifestations were similar. Patients with bloodstream infection should subject to microbiological testing and be treated with appropriate active agents as soon as possible to reduce fatality rate.%目的 探讨铜绿假单胞菌血流感染的临床特点及细菌耐药性.方法 回顾性分析北京大学第三医院2006年1月-2009年12月铜绿假单胞菌血流感染患者的临床及微生物学资料.结果 27例患者纳入分

  3. [Diagnosis, therapy and prevention of respiratory virus infections in lung transplant recipients].

    Science.gov (United States)

    Huber, Lars C; Isenring, Bruno D; Schuurmans, Macé M

    2014-04-09

    Lung transplant recipients have a life-long profound immunosuppression which makes them prone to respiratory tract infections, in particular viral infections during the winter season. Since the respiratory tract infections may have potentially severe consequences, we recommend early diagnosis and treatment. We obtain nasopharyngeal swabs for viral and bacteriological examination and then treat pre-emptively with antivirals, broad-band antibiotics and often also with intravenous immunoglobulins. Treatment duration is often longer than in immunocompetent patients. As preventive measures we provide vaccination against seasonal influenza and recommend specific daily hygiene measures.

  4. Treatment of Severe Post-kidney-transplant Lung Infection by Integrative Chinese and Western Medicine

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective: To explore treatments of severe post-kidney-transplant lung infection by integrative Chinese and Western medicine (ICWM), in order to elevate the curing rate as well as to lower the death rate. Methods: Based on conventional ways of Western medical treatments of 18 cases of severe post-kidney-transplant lung infection, such as putting the patients in single individual ward, antibiotics to prevent infection, respiratory machines, blood filtration, nutritional support, steroids, and maintaining electrolytes balance, we applied integrated Chinese medicinal treatments, like altering conventional prescription "pneumonia Ⅲ ", and conducted clinical observation of effectiveness, and indexes including white blood cell (WBC), neutrophilic granulocyte, blood urea nitrogen (BUN), blood creatinine (Cr), etc. Results: Of the 18cases studied, 7 were already cured, 8 proved the treatment effective, 3 died. All clinical indexes had statistically significant changes compared with those of before treatment (P<0.01). Conclusion: ICWM can increase curing rate and lower death rate.

  5. Nocardia farcinica lung infection in a patient with cystic fibrosis: a case report

    Directory of Open Access Journals (Sweden)

    Rolain Jean-Marc

    2010-03-01

    Full Text Available Abstract Introduction Respiratory tract infections are the major causes of morbidity and mortality in patients with cystic fibrosis. Nocardia are rarely implicated in these infections and few reports of the involvement of this species are found in the literature. Case presentation We describe a case of lung infection followed by chronic colonization of trimethoprim and sulfamethoxazole resistant Nocardia farcinica in a patient with cystic fibrosis. The chronic colonization of this uncommon bacterium in patients with cystic fibrosis was proved using a newly developed real-time polymerase chain reaction assay, which indicates that this bacterium, despite treatment, is difficult to eradicate. Conclusion Our case report confirms that this organism can be recovered in persons with cystic fibrosis. Its eradication is necessary especially if the patient is to undergo lung transplantation.

  6. Spatiotemporal quantification of cell dynamics in the lung following influenza virus infection

    Science.gov (United States)

    Yin, Lu; Xu, Shuoyu; Cheng, Jierong; Zheng, Dahai; Limmon, Gino V.; Leung, Nicola H. N.; Rajapakse, Jagath C.; Chow, Vincent T. K.; Chen, Jianzhu; Yu, Hanry

    2013-04-01

    Lung injury caused by influenza virus infection is widespread. Understanding lung damage and repair progression post infection requires quantitative spatiotemporal information on various cell types mapping into the tissue structure. Based on high content images acquired from an automatic slide scanner, we have developed algorithms to quantify cell infiltration in the lung, loss and recovery of Clara cells in the damaged bronchioles and alveolar type II cells (AT2s) in the damaged alveolar areas, and induction of pro-surfactant protein C (pro-SPC)-expressing bronchiolar epithelial cells (SBECs). These quantitative analyses reveal: prolonged immune cell infiltration into the lung that persisted long after the influenza virus was cleared and paralleled with Clara cell recovery; more rapid loss and recovery of Clara cells as compared to AT2s; and two stages of SBECs from Scgb1a1+ to Scgb1a1-. These results provide evidence supporting a new mechanism of alveolar repair where Clara cells give rise to AT2s through the SBEC intermediates and shed light on the understanding of the lung damage and repair process. The approach and algorithms in quantifying cell-level changes in the tissue context (cell-based tissue informatics) to gain mechanistic insights into the damage and repair process can be expanded and adapted in studying other disease models.

  7. Biological efficacy and stability of diluted ticarcillin-clavulanic acid in the topical treatment of Pseudomonas aeruginosa infections.

    Science.gov (United States)

    Bateman, Fiona L; Moss, Susan M; Trott, Darren J; Shipstone, Michael A

    2012-04-01

    Topical compounded Timentin(®) diluted with an inactive vehicle has been reported to be effective in the treatment of otitis externa caused by Pseudomonas aeruginosa. The aims of this study were to determine the biological efficacy of Timentin(®) (ticarcillin and clavulanic acid) when diluted in the carrier vehicle Methopt(®) against P. aeruginosa and to determine the efficacy and stability of Timentin(®) aqueous stock concentrate solution. Timentin(®) stock concentrate was tested against four P. aeruginosa isolates on days 0, 7, 14, 21 and 28; then after 2, 3, 4, 5, 6, 9 and 12 months of storage at 4 or -20°C. The diluted Timentin(®)-Methopt(®) solutions were tested against all isolates after 0, 2, 4, 6, 8, 10, 12, 14, 17, 21, 24 and 28 days of storage at 24 or 4°C. Minimal inhibitory concentration (MIC) levels for all strains were determined using the broth microdilution method. The MIC of the stock solution remained relatively constant and acceptable throughout the study when stored at -20°C and was also acceptable for shorter time periods (6-9 months) when stored at 4°C. The MIC for the diluted Timentin(®)-Methopt(®) solution remained relatively constant and acceptable throughout the study for all four bacterial strains, with no difference between the solutions stored at 4 or 24°C. The results of this study indicate that storage of the Timentin(®) stock solution at -20°C does not compromise efficacy for at least 12 months and that Timentin(®) diluted in Methopt(®) was stable for 28 days when stored at either 4 or 24°C.

  8. Immunization with Pseudomonas aeruginosa vaccines and adjuvant can modulate the type of inflammatory response subsequent to infection

    DEFF Research Database (Denmark)

    Johansen, H K; Espersen, F; Cryz, S J

    1994-01-01

    immunized with P. aeruginosa whole-cell sonicates, O-polysaccharide toxin A conjugate, an alginate-toxin A conjugate, or native alginate. Control animals received sterile saline or incomplete Freund's adjuvant (IFA). The macroscopic (mean score, 2.4 versus 2.7 to 3.2) (P .... The histopathologic results in the saline control rats were characterized by acute inflammation dominated by numerous polymorphonuclear leukocytes surrounding the alginate beads (microcolonies), as in CF patients. In contrast, the inflammatory response in the IFA group and in the immunized rats had changed from...

  9. Proteoglycans: key regulators of pulmonary inflammation and the innate immune response to lung infection.

    Science.gov (United States)

    Gill, Sean; Wight, Thomas N; Frevert, Charles W

    2010-06-01

    Exposure to viruses and bacteria results in lung infections and places a significant burden on public health. The innate immune system is an early warning system that recognizes viruses and bacteria, which results in the rapid production of inflammatory mediators such as cytokines and chemokines and the pulmonary recruitment of leukocytes. When leukocytes emigrate from the systemic circulation through the extracellular matrix (ECM) in response to lung infection they encounter proteoglycans, which consist of a core protein and their associated glycosaminoglycans. In this review, we discuss how proteoglycans serve to modify the pulmonary inflammatory response and leukocyte migration through a number of different mechanisms including: (1) The ability of soluble proteoglycans or fragments of glycosaminoglycans to activate Toll-like receptor (TLRs) signaling pathways; (2) The binding and sequestration of cytokines, chemokines, and growth factors by proteoglycans; (3) the ability of proteoglycans and hyaluronan to facilitate leukocyte adhesion and sequestration; and (4) The interactions between proteoglycans and matrix metalloproteinases (MMP) that alter the function of these proteases. In conclusion, proteoglycans fine-tune tissue inflammation through a number of different mechanisms. Clarification of the mechanisms whereby proteoglycans modulate the pulmonary inflammatory response will most likely lead to new therapeutic approaches to inflammatory lung disease and lung infection.

  10. Neutrophil elastase causes tissue damage that decreases host tolerance to lung infection with burkholderia species.

    Directory of Open Access Journals (Sweden)

    Manoranjan Sahoo

    2014-08-01

    Full Text Available Two distinct defense strategies can protect the host from infection: resistance is the ability to destroy the infectious agent, and tolerance is the ability to withstand infection by minimizing the negative impact it has on the host's health without directly affecting pathogen burden. Burkholderia pseudomallei is a Gram-negative bacterium that infects macrophages and causes melioidosis. We have recently shown that inflammasome-triggered pyroptosis and IL-18 are equally important for resistance to B. pseudomallei, whereas IL-1β is deleterious. Here we show that the detrimental role of IL-1β during infection with B. pseudomallei (and closely related B. thailandensis is due to excessive recruitment of neutrophils to the lung and consequent tissue damage. Mice deficient in the potentially damaging enzyme neutrophil elastase were less susceptible than the wild type C57BL/6J mice to infection, although the bacterial burdens in organs and the extent of inflammation were comparable between C57BL/6J and elastase-deficient mice. In contrast, lung tissue damage and vascular leakage were drastically reduced in elastase-deficient mice compared to controls. Bradykinin levels were higher in C57BL/6 than in elastase-deficient mice; administration of a bradykinin antagonist protected mice from infection, suggesting that increased vascular permeability mediated by bradykinin is one of the mechanisms through which elastase decreases host tolerance to melioidosis. Collectively, these results demonstrate that absence of neutrophil elastase increases host tolerance, rather than resistance, to infection by minimizing host tissue damage.

  11. Candida albicans and Pseudomonas aeruginosa Interaction, with Focus on the Role of Eicosanoids.

    Science.gov (United States)

    Fourie, Ruan; Ells, Ruan; Swart, Chantel W; Sebolai, Olihile M; Albertyn, Jacobus; Pohl, Carolina H

    2016-01-01

    Candida albicans is commonly found in mixed infections with Pseudomonas aeruginosa, especially in the lungs of cystic fibrosis (CF) patients. Both of these opportunistic pathogens are able to form resistant biofilms and frequently infect immunocompromised individuals. The interaction between these two pathogens, which includes physical interaction as well as secreted factors, is mainly antagonistic. In addition, research suggests considerable interaction with their host, especially with immunomodulatory lipid mediators, termed eicosanoids. Candida albicans and Pseudomonas aeruginosa are both able to utilize arachidonic acid (AA), liberated from the host cells during infection, to form eicosanoids. The production of these eicosanoids, such as Prostaglandin E2, by the host and the pathogens may affect the dynamics of polymicrobial infection and the outcome of infections. It is of considerable importance to elucidate the role of host-produced, as well as pathogen-produced eicosanoids in polymicrobial infection. This review will focus on in vitro as well as in vivo interaction between C. albicans and P. aeruginosa, paying special attention to the role of eicosanoids in the cross-talk between host and the pathogens.

  12. [Opportunistic lung infections in patients with chronic obstructive lung disease; a side effect of inhalation corticosteroids?].

    Science.gov (United States)

    Smeenk, F W; Klinkhamer, P J; Breed, W; Jansz, A R; Jansveld, C A

    1996-01-13

    In four patients, men of 64, 66 and 69 years old and a woman of 65 years, who suffered from chronic obstructive pulmonary disease (COPD) and used inhalation corticosteroids in a relatively high dose (800-1600 micrograms of budesonide per day), a pulmonary infection was diagnosed caused by Mycobacterium malmoense (the first two patients) and Aspergillus (the other two) respectively. Inhalation corticosteroids are of great importance in the treatment of asthmatic patients. Their place in the treatment of patients with COPD is much less clear. The patients did not have an immunological deficiency or anatomical pulmonary or bronchial deformation which could have explained the occurrence of these infections. The high dosages of inhalation corticosteroids may have been involved in the cause of these infections by suppressing the T-cell response locally. In view of this, longterm inhalation corticosteroid treatment should be prescribed in COPD patients only if the efficacy of the medication has been proved in the individual patient involved.

  13. LasR Variant Cystic Fibrosis Isolates Reveal an Adaptable Quorum-Sensing Hierarchy in Pseudomonas aeruginosa

    Science.gov (United States)

    Feltner, John B.; Wolter, Daniel J.; Pope, Christopher E.; Groleau, Marie-Christine; Smalley, Nicole E.; Greenberg, E. Peter; Mayer-Hamblett, Nicole; Burns, Jane; Hoffman, Lucas R.

    2016-01-01

    ABSTRACT Chronic Pseudomonas aeruginosa infections cause significant morbidity in patients with cystic fibrosis (CF). Over years to decades, P. aeruginosa adapts genetically as it establishes chronic lung infections. Nonsynonymous mutations in lasR, the quorum-sensing (QS) master regulator, are common in CF. In laboratory strains of P. aeruginosa, LasR activates transcription of dozens of genes, including that for another QS regulator, RhlR. Despite the frequency with which lasR coding variants have been reported to occur in P. aeruginosa CF isolates, little is known about their consequences for QS. We sequenced lasR from 2,583 P. aeruginosa CF isolates. The lasR sequences of 580 isolates (22%) coded for polypeptides that differed from the conserved LasR polypeptides of well-studied laboratory strains. This collection included 173 unique lasR coding variants, 116 of which were either missense or nonsense mutations. We studied 31 of these variants. About one-sixth of the variant LasR proteins were functional, including 3 with nonsense mutations, and in some LasR-null isolates, genes that are LasR dependent in laboratory strains were nonetheless expressed. Furthermore, about half of the LasR-null isolates retained RhlR activity. Therefore, in some CF isolates the QS hierarchy is altered such that RhlR quorum sensing is independent of LasR regulation. Our analysis challenges the view that QS-silent P. aeruginosa is selected during the course of a chronic CF lung infection. Rather, some lasR sequence variants retain functionality, and many employ an alternate QS strategy involving RhlR. PMID:27703072

  14. Candida albicans ethanol stimulates Pseudomonas aeruginosa WspR-controlled biofilm formation as part of a cyclic relationship involving phenazines.

    Directory of Open Access Journals (Sweden)

    Annie I Chen

    2014-10-01

    Full Text Available In chronic infections, pathogens are often in the presence of other microbial species. For example, Pseudomonas aeruginosa is a common and detrimental lung pathogen in individuals with cystic fibrosis (CF and co-infections with Candida albicans are common. Here, we show that P. aeruginosa biofilm formation and phenazine production were strongly influenced by ethanol produced by the fungus C. albicans. Ethanol stimulated phenotypes that are indicative of increased levels of cyclic-di-GMP (c-di-GMP, and levels of c-di-GMP were 2-fold higher in the presence of ethanol. Through a genetic screen, we found that the diguanylate cyclase WspR was required for ethanol stimulation of c-di-GMP. Multiple lines of evidence indicate that ethanol stimulates WspR signaling through its cognate sensor WspA, and promotes WspR-dependent activation of Pel exopolysaccharide production, which contributes to biofilm maturation. We also found that ethanol stimulation of WspR promoted P. aeruginosa colonization of CF airway epithelial cells. P. aeruginosa production of phenazines occurs both in the CF lung and in culture, and phenazines enhance ethanol production by C. albicans. Using a C. albicans adh1/adh1 mutant with decreased ethanol production, we found that fungal ethanol strongly altered the spectrum of P. aeruginosa phenazines in favor of those that are most effective against fungi. Thus, a feedback cycle comprised of ethanol and phenazines drives this polymicrobial interaction, and these relationships may provide insight into why co-infection with both P. aeruginosa and C. albicans has been associated with worse outcomes in cystic fibrosis.

  15. Respiratory Failure due to Possible Donor-Derived Sporothrix schenckii Infection in a Lung Transplant Recipient

    Directory of Open Access Journals (Sweden)

    Nathan C. Bahr

    2015-01-01

    Full Text Available Background. De novo and donor-derived invasive fungal infections (IFIs contribute to morbidity and mortality in solid organ transplant (SOT recipients. Reporting of donor-derived IFIs (DDIFIs to the Organ Procurement Transplant Network has been mandated since 2005. Prior to that time no systematic monitoring of DDIFIs occurred in the United States. Case Presentation. We report a case of primary graft dysfunction in a 49-year-old male lung transplant recipient with diffuse patchy bilateral infiltrates likely related to pulmonary Sporothrix schenckii infection. The organism was isolated from a bronchoalveolar lavage on the second day after transplantation. Clinical and radiographic responses occurred after initiation of amphotericin B lipid formulation. Conclusion. We believe that this was likely a donor-derived infection given the early timing of the Sporothrix isolation after transplant in a bilateral single lung transplant recipient. This is the first case report of sporotrichosis in a lung transplant recipient. Our patient responded well to amphotericin induction therapy followed by maintenance therapy with itraconazole. The implications of donor-derived fungal infections and Sporothrix in transplant recipients are reviewed. Early recognition and management of these fungi are essential in improving outcomes.

  16. Respiratory Failure due to Possible Donor-Derived Sporothrix schenckii Infection in a Lung Transplant Recipient.

    Science.gov (United States)

    Bahr, Nathan C; Janssen, Katherine; Billings, Joanne; Loor, Gabriel; Green, Jaime S

    2015-01-01

    Background. De novo and donor-derived invasive fungal infections (IFIs) contribute to morbidity and mortality in solid organ transplant (SOT) recipients. Reporting of donor-derived IFIs (DDIFIs) to the Organ Procurement Transplant Network has been mandated since 2005. Prior to that time no systematic monitoring of DDIFIs occurred in the United States. Case Presentation. We report a case of primary graft dysfunction in a 49-year-old male lung transplant recipient with diffuse patchy bilateral infiltrates likely related to pulmonary Sporothrix schenckii infection. The organism was isolated from a bronchoalveolar lavage on the second day after transplantation. Clinical and radiographic responses occurred after initiation of amphotericin B lipid formulation. Conclusion. We believe that this was likely a donor-derived infection given the early timing of the Sporothrix isolation after transplant in a bilateral single lung transplant recipient. This is the first case report of sporotrichosis in a lung transplant recipient. Our patient responded well to amphotericin induction therapy followed by maintenance therapy with itraconazole. The implications of donor-derived fungal infections and Sporothrix in transplant recipients are reviewed. Early recognition and management of these fungi are essential in improving outcomes.

  17. Detection of blaSPM-1, blaKPC, blaTEM and blaCTX-M genes in isolates of Pseudomonas aeruginosa, Acinetobacter spp. and Klebsiella spp. from cancer patients with healthcare-associated infections.

    Science.gov (United States)

    Jácome, Paula Regina Luna de Araújo; Alves, Lílian Rodrigues; Jácome-Júnior, Agenor Tavares; Silva, Maria Jesuíta Bezerra da; Lima, Jailton Lobo da Costa; Araújo, Paulo Sérgio Ramos; Lopes, Ana Catarina S; Maciel, Maria Amélia Vieira

    2016-07-01

    Pseudomonas aeruginosa, Acinetobacter spp. and Klebsiella spp. are three of the pathogens most frequently involved in infections of cancer patients, and the production of β -lactamases is a major mechanism of resistance due to its wide diversity of existing enzymes. Therefore, the aim of the present study was to investigate the microbiological profile and data related to patients and infections, and to search for β -lactamase genes in bacterial isolates from hospitalized cancer patients in a hospital in Recife, Pernambuco, Brazil. A total of 169 isolates were recovered between 2012 and 2014, of which 58 were P. aeruginosa, 36 were Acinetobacter spp. and 75 were Klebsiella spp. A high percentage of carbapenem resistance was observed in P. aeruginosa and Acinetobacter spp. Among the carbapenem-resistant bacteria, the blaSPM-1 gene was detected in P. aeruginosa (35.5 %) and Acinetobacter spp. (3.8 %), while blaKPC was detected in P. aeruginosa (25.8 %) only. Among the third- and fourth-generation cephalosporin-resistant strains, in Klebsiella spp. we detected the genes blaTEM (30.6 %), blaCTX-M (58.3 %) and blaKPC (5.6 %), and in Acinetobacter spp. only blaTEM (25.9 %). This the first report of an Acinetobacter baumannii blaSPM-1 gene carrier that has been isolated in Brazil. The most frequent cancer types were bowel tumour [14.8 %; 95 % confidence interval (CI95 %) 9.8-21.1 %], breast cancer (13.6 %; CI95 % 8.8-19.7 %) and prostate cancer (11.2%; CI95 % 6.9-17.0 %). These results therefore provide knowledge of susceptibility profile and resistance mechanisms and thus can contribute to the strategic formulation of hospital infection control plans and the rational use of antimicrobials, reducing mortality from infection levels in cancer patients.

  18. Dysregulation of beta-chemokines in the lungs of HIV-1-infected patients.

    Science.gov (United States)

    Aung, H; McKenna, S M; Ketoff, N R; Jones, L; Wu, M; Hejal, R; Rich, E A; Toossi, Z

    2001-04-01

    The beta-chemokines, macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, monocyte chemotactic protein (MCP)-1 and regulated-on-activation normal T cell, expressed and secreted (RANTES) are not only chemotactic for mononuclear cells but may be important in suppression of HIV-1 replication through competitive binding to the chemokine receptor, CCR5, which is critical to viral entry. In this study, bronchoalveolar cells (BACs) and autologous peripheral blood mononuclear cells (PBMCs) were obtained from HIV-1-infected participants who did not manifest clinical signs of lung disease with peripheral CD4 T-cell count >200/mm(3) (n = 7, group with high CD4 count), or CD4 T-cell count CCR5 was assessed. Induction of MIP-1 alpha by lipopolysaccharide (LPS) in BAC of HIV-1-infected study subjects from the low CD4 group was less than BAC from healthy study subjects (p HIV-1-infected patients was significantly less than that from healthy study subjects (p CCR5 and MIP-1 alpha in BAC was significantly lower in HIV-1-infected patients compared with in healthy study subjects (p HIV-1-infected patients with high CD4 count was significantly higher than healthy study subjects (p HIV-1 infection in the lung.

  19. QapR (PA5506) represses an operon that negatively affects the Pseudomonas quinolone signal in Pseudomonas aeruginosa.

    Science.gov (United States)

    Tipton, Kyle A; Coleman, James P; Pesci, Everett C

    2013-08-01

    Pseudomonas aeruginosa is a Gram-negative, opportunistic pathogen that can cause disease in varied sites within the human body and is a significant source of morbidity and mortality in those afflicted with cystic fibrosis. P. aeruginosa is able to coordinate group behaviors, such as virulence factor production, through the process of cell-to-cell signaling. There are three intercellular signaling systems employed by P. aeruginosa, and one of these systems utilizes the small molecule 2-heptyl-3-hydroxy-4-quinolone (Pseudomonas quinolone signal [PQS]). PQS is required for virulence in multiple infection models and has been found in the lungs of cystic fibrosis patients colonized by P. aeruginosa. In this study, we have identified an RpiR family transcriptional regulator, QapR, which is an autoregulatory repressor. We found that mutation of qapR caused overexpression of the qapR operon. We characterized the qapR operon to show that it contains genes qapR, PA5507, PA5508, and PA5509 and that QapR directly controls the transcription of these genes in a negative manner. We also show that derepression of this operon greatly reduces PQS concentration in P. aeruginosa. Our results suggest that qapR affects PQS concentration by repressing an enzymatic pathway that acts on PQS or a PQS precursor to lower the PQS concentration. We believe that this operon comprises a novel mechanism to regulate PQS concentration in P. aeruginosa.

  20. Paragonimus westermani infection in lung: A confounding diagnostic entity

    Directory of Open Access Journals (Sweden)

    Shivani Kalhan

    2015-01-01

    Full Text Available Paragonimiasis is a food-borne parasitic zoonosis caused by the genus Paragonimus. Fresh water snails, crabs, and crayfish are the first and second intermediate hosts, respectively. Humans acquire this infection by ingesting uncooked/undercooked crustaceans. Laboratory diagnosis of Paragonimiasis is done by demonstration of ova in the sputum/feces/pleural fluid or by serology. A case of pulmonary Paragonimiasis is presented herewith; the patient having been diagnosed with pulmonary tuberculosis earlier. The aim of this presentation is to highlight this entity so that it is considered in the differential diagnosis in a case of hemoptysis.

  1. Paragonimus westermani infection in lung: A confounding diagnostic entity

    Science.gov (United States)

    Kalhan, Shivani; Sharma, Pankaj; Sharma, Sonia; Kakria, Neha; Dudani, Sharmila; Gupta, Anshu

    2015-01-01

    Paragonimiasis is a food-borne parasitic zoonosis caused by the genus Paragonimus. Fresh water snails, crabs, and crayfish are the first and second intermediate hosts, respectively. Humans acquire this infection by ingesting uncooked/undercooked crustaceans. Laboratory diagnosis of Paragonimiasis is done by demonstration of ova in the sputum/feces/pleural fluid or by serology. A case of pulmonary Paragonimiasis is presented herewith; the patient having been diagnosed with pulmonary tuberculosis earlier. The aim of this presentation is to highlight this entity so that it is considered in the differential diagnosis in a case of hemoptysis. PMID:25983414

  2. Quantitative proteome profiling of respiratory virus-infected lung epithelial cells.

    Science.gov (United States)

    van Diepen, Angela; Brand, H Kim; Sama, Iziah; Lambooy, Lambert H J; van den Heuvel, Lambert P; van der Well, Leontine; Huynen, Martijn; Osterhaus, Albert D M E; Andeweg, Arno C; Hermans, Peter W M

    2010-08-05

    Respiratory virus infections are among the primary causes of morbidity and mortality in humans. Influenza virus, respiratory syncytial virus (RSV), parainfluenza (PIV) and human metapneumovirus (hMPV) are major causes of respiratory illness in humans. Especially young children and the elderly are susceptible to infections with these viruses. In this study we aim to gain detailed insight into the molecular pathogenesis of respiratory virus infections by studying the protein expression profiles of infected lung epithelial cells. A549 cells were exposed to a set of respiratory viruses [RSV, hMPV, PIV and Measles virus (MV)] using both live and UV-inactivated virus preparations. Cells were harvested at different time points after infection and processed for proteomics analysis by 2-dimensional difference gel electrophoresis. Samples derived from infected cells were compared to mock-infected cells to identify proteins that are differentially expressed due to infection. We show that RSV, hMPV, PIV3, and MV induced similar core host responses and that mainly proteins involved in defense against ER stress and apoptosis were affected which points towards an induction of apoptosis upon infection. By 2-D DIGE analyses we have gathered information on the induction of apoptosis by respiratory viruses in A549 cells.

  3. Persistent activation of an innate immune response translates respiratory viral infection into chronic lung disease.

    Science.gov (United States)

    Kim, Edy Y; Battaile, John T; Patel, Anand C; You, Yingjian; Agapov, Eugene; Grayson, Mitchell H; Benoit, Loralyn A; Byers, Derek E; Alevy, Yael; Tucker, Jennifer; Swanson, Suzanne; Tidwell, Rose; Tyner, Jeffrey W; Morton, Jeffrey D; Castro, Mario; Polineni, Deepika; Patterson, G Alexander; Schwendener, Reto A; Allard, John D; Peltz, Gary; Holtzman, Michael J

    2008-06-01

    To understand the pathogenesis of chronic inflammatory disease, we analyzed an experimental mouse model of chronic lung disease with pathology that resembles asthma and chronic obstructive pulmonary disease (COPD) in humans. In this model, chronic lung disease develops after an infection with a common type of respiratory virus is cleared to only trace levels of noninfectious virus. Chronic inflammatory disease is generally thought to depend on an altered adaptive immune response. However, here we find that this type of disease arises independently of an adaptive immune response and is driven instead by interleukin-13 produced by macrophages that have been stimulated by CD1d-dependent T cell receptor-invariant natural killer T (NKT) cells. This innate immune axis is also activated in the lungs of humans with chronic airway disease due to asthma or COPD. These findings provide new insight into the pathogenesis of chronic inflammatory disease with the discovery that the transition from respiratory viral infection into chronic lung disease requires persistent activation of a previously undescribed NKT cell-macrophage innate immune axis.

  4. Interstitial lung disease associated with Equine Infectious Anemia Virus infection in horses.

    Science.gov (United States)

    Bolfa, Pompei; Nolf, Marie; Cadoré, Jean-Luc; Catoi, Cornel; Archer, Fabienne; Dolmazon, Christine; Mornex, Jean-François; Leroux, Caroline

    2013-12-01

    EIA (Equine Infectious Anemia) is a blood-borne disease primarily transmitted by haematophagous insects or needle punctures. Other routes of transmission have been poorly explored. We evaluated the potential of EIAV (Equine Infectious Anemia Virus) to induce pulmonary lesions in naturally infected equids. Lungs from 77 EIAV seropositive horses have been collected in Romania and France. Three types of lesions have been scored on paraffin-embedded lungs: lymphocyte infiltration, bronchiolar inflammation, and thickness of the alveolar septa. Expression of the p26 EIAV capsid (CA) protein has been evaluated by immunostaining. Compared to EIAV-negative horses, 52% of the EIAV-positive horses displayed a mild inflammation around the bronchioles, 22% had a moderate inflammation with inflammatory cells inside the wall and epithelial bronchiolar hyperplasia and 6.5% had a moderate to severe inflammation, with destruction of the bronchiolar epithelium and accumulation of smooth muscle cells within the pulmonary parenchyma. Changes in the thickness of the alveolar septa were also present. Expression of EIAV capsid has been evidenced in macrophages, endothelial as well as in alveolar and bronchiolar epithelial cells, as determined by their morphology and localization. To summarize, we found lesions of interstitial lung disease similar to that observed during other lentiviral infections such as FIV in cats, SRLV in sheep and goats or HIV in children. The presence of EIAV capsid in lung epithelial cells suggests that EIAV might be responsible for the broncho-interstitial damages observed.

  5. Novel Path Towards Colistin Resistance In Pseudomonas Aeruginosa During Chronic Infection Involves Polymorphisms In Uncharacterized Glycosyltransferase Gene

    DEFF Research Database (Denmark)

    Hermansen, Grith Miriam Maigaard; Jelsbak, Lars

    2015-01-01

    Introduction: Antibiotic resistance development in the gram-negative bacterium Pseudomonas aeruginosa is an increasing problem. The effect of colistin, one of the few last resort drugs commonly given to cystic fibrosis (CF) patients, is dependent on the lipopolysaccharide (LPS) structure. We have....... The results indicate that this glycosyltransferase polymorphism is needed for the clinical strain to be fully virulent. However, introducing the SNP into PAO1 did not result in altered phenotypes. These results reveal this uncharacterized glycosyltransferase as a novel in vivo path to colistin resistance...... by LPS modification. Conclusions: Colistin resistance development in vivo occurs via multiple paths. Here a novel pathway for the development of colistin resistance was described. It involves mutations in a hitherto uncharacterized glycosyltransferase....

  6. Systemic signature of the lung response to respiratory syncytial virus infection.

    Directory of Open Access Journals (Sweden)

    Jeroen L A Pennings

    Full Text Available Respiratory Syncytial Virus is a frequent cause of severe bronchiolitis in children. To improve our understanding of systemic host responses to RSV, we compared BALB/c mouse gene expression responses at day 1, 2, and 5 during primary RSV infection in lung, bronchial lymph nodes, and blood. We identified a set of 53 interferon-associated and innate immunity genes that give correlated responses in all three murine tissues. Additionally, we identified blood gene signatures that are indicative of acute infection, secondary immune response, and vaccine-enhanced disease, respectively. Eosinophil-associated ribonucleases were characteristic for the vaccine-enhanced disease blood signature. These results indicate that it may be possible to distinguish protective and unfavorable patient lung responses via blood diagnostics.

  7. 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.

  8. Lung fibrosis in deceased HIV-infected patients with Pneumocystis pneumonia

    Directory of Open Access Journals (Sweden)

    Erica J Shaddock

    2012-06-01

    Full Text Available Background. Pneumocystis pneumonia (PcP is one of the most common opportunistic infections found in patients with HIV. The prognosis if ventilation is required is poor, with mortality of 36 - 80%. Although more recent studies have shown improved survival, our experience has been that close to 100% of such patients die, and we therefore decided to investigate further. Methods. All patients with confirmed or suspected PcP who died owing to respiratory failure were eligible for the study. Where consent was obtained, trucut lung biopsies were performed post mortem, stored in formalin and sent for histopathological assessment. Results. Twelve adequate lung biopsies were obtained from 1 July 2008 to 28 February 2011 – 3 from men and 9 from women. The mean age was 34.7 years (range 24 - 46, and the mean admission CD4 count was 20.8 (range 1 - 68 cells/μl and median 18.5 cells/μl. All specimens demonstrated typical PcP histopathology; in addition, 9 showed significant interstitial fibrosis. Three had co-infection with cytomegalovirus (CMV, two of which had fibrosis present. There was no evidence of TB or other fungal infections. Conclusion. The high mortality seen in this cohort of PcP patients was due to intractable respiratory failure from interstitial lung fibrosis. whereas the differential includes ventilator induced lung injury, drug resistance or co-infections, we suggest that this is part of the disease progression in certain individuals. Further studies are required to identify interventions that could modify this process and improve outcomes in patients with PcP who require mechanical ventilation. S Afr J HIV Med 2012;13(2:64-67.

  9. High-resolution computed tomography (HRCT) of lung infections in non-AIDS immunocompromised patients

    Energy Technology Data Exchange (ETDEWEB)

    Franquet, Tomas [Universitat Autonoma de Barcelona, Department of Radiology, Thoracic Radiology Section, Hospital de Sant Pau, Barcelona (Spain)

    2006-03-15

    Non-AIDS immunocompromised patients are susceptible to infections by a wide range of organisms. In the past several decades, advances in the treatment of cancer, organ transplantation, and immunosuppressive therapy have resulted in large numbers of patients who develop abnormalities in their immune system. Moreover, mildly impaired host immunity as it occurs in chronic debilitating illness, diabetes mellitus, malnutrition, alcoholism, advanced age, prolonged corticosteroid administration, and chronic obstructive lung disease have also been regarded as predisposing factors of pulmonary infections. Imaging plays a crucial role in the detection and management of patients with pulmonary infectious diseases. When pulmonary infection is suspected, knowledge of the varied radiographic manifestations will narrow the differential diagnosis, helping to direct additional diagnostic measures and serving as an ideal tool for follow-up examinations. Combination of pattern recognition with knowledge of the clinical setting is the best approach to pulmonary infection occurring in the immunocompromised patients. (orig.)

  10. Pulmonary bacteriophage therapy on Pseudomonas aeruginosa cystic fibrosis strains: first steps towards treatment and prevention.

    Directory of Open Access Journals (Sweden)

    Eric Morello

    Full Text Available Multidrug-resistant bacteria are the cause of an increasing number of deadly pulmonary infections. Because there is currently a paucity of novel antibiotics, phage therapy--the use of specific viruses that infect bacteria--is now more frequently being considered as a potential treatment for bacterial infections. Using a mouse lung-infection model caused by a multidrug resistant Pseudomonas aeruginosa mucoid strain isolated from a cystic fibrosis patient, we evaluated bacteriophage treatments. New bacteriophages were isolated from environmental samples and characterized. Bacteria and bacteriophages were applied intranasally to the immunocompetent mice. Survival was monitored and bronchoalveolar fluids were analysed. Quantification of bacteria, bacteriophages, pro-inflammatory and cytotoxicity markers, as well as histology and immunohistochemistry analyses were performed. A curative treatment (one single dose administrated 2 h after the onset of the infection allowed over 95% survival. A four-day preventive treatment (one single dose resulted in a 100% survival. All of the parameters measured correlated with the efficacy of both curative and preventive bacteriophage treatments. We also showed that in vitro optimization of a bacteriophage towards a clinical strain improved both its efficacy on in vivo treatments and its host range on a panel of 20 P. aeruginosa cystic fibrosis strains. This work provides an incentive to develop clinical studies on pulmonary bacteriophage therapy to combat multidrug-resistant lung infections.

  11. Lung function and bronchial responsiveness after Mycoplasma pneumoniae infection in early childhood

    DEFF Research Database (Denmark)

    Boysen, Birgitte Kjær; Jensen, Jørgen S; Nielsen, Kim G

    2008-01-01

    Mycoplasma (M.) pneumoniae has been associated with exacerbation of symptoms in asthmatic school children and adults; and an etiological role in asthma has been suggested. The purpose of this study was to investigate whether infection with M. pneumoniae in early childhood has a long-term influenc...... 1.21 (kPa sec), P = 0.45; and mean change in specific resistance was 13% versus 9%, P = 0.42. In conclusion, M. pneumoniae infection in early childhood was not associated with long-term effects on lung function and bronchial hyperresponsiveness 2 years after infection.......Mycoplasma (M.) pneumoniae has been associated with exacerbation of symptoms in asthmatic school children and adults; and an etiological role in asthma has been suggested. The purpose of this study was to investigate whether infection with M. pneumoniae in early childhood has a long-term influence...... on lung function and bronchial responsiveness. In a retrospective, clinical cohort-study children younger than 5 years-of-age when PCR-tested for M. pneumoniae were enrolled. Sixty-five children with clinical symptoms suggesting infection with M. pneumoniae during an epidemic season completed a clinical...

  12. siRNA-mediated gene silencing of MexB from the MexA-MexB-OprM efflux pump in Pseudomonas aeruginosa.

    Science.gov (United States)

    Gong, Feng-Yun; Zhang, Ding-Yu; Zhang, Jiang-Guo; Wang, Li-Li; Zhan, Wei-Li; Qi, Jun-Ying; Song, Jian-Xin

    2014-04-01

    To gain insights into the effect of MexB gene under the short interfering RNA (siRNA), we synthesized 21 bp siRNA duplexes against the MexB gene. RT-PCR was performed to determine whether the siRNA inhibited the expression of MexB mRNA. Changes in antibiotic susceptibility in response to siRNA were measured by the E-test method. The efficacy of siRNAs was determined in a murine model of chronic P. aeruginosa lung infection. MexB-siRNAs inhibited both mRNA expression and the activity of P. aeruginosa in vitro. In vivo, siRNA was effective in reducing the bacterial load in the model of chronic lung infection and the P. aeruginosa-induced pathological changes. MexB-siRNA treatment enhanced the production of inflammatory cytokines in the early infection stage (P<0.05). Our results suggest that targeting of MexB with siRNA appears to be a novel strategy for treating P. aeruginosa infections.

  13. Toxicogenomic response of Pseudomonas aeruginosa to ortho-phenylphenol

    Directory of Open Access Journals (Sweden)

    Toghrol Freshteh

    2008-10-01

    Full Text Available Abstract Background Pseudomonas aeruginosa (P. aeruginosa is the most common opportunistic pathogen implicated in nosocomial infections and in chronic lung infections in cystic fibrosis patients. Ortho-phenylphenol (OPP is an antimicrobial agent used as an active ingredient in several EPA registered disinfectants. Despite its widespread use, there is a paucity of information on its target molecular pathways and the cellular responses that it elucidates in bacteria in general and in P. aeruginosa in particular. An understanding of the OPP-driven gene regulation and cellular response it elicits will facilitate more effective utilization of this antimicrobial and possibly lead to the development of more effective disinfectant treatments. Results Herein, we performed a genome-wide transcriptome analysis of the cellular responses of P. aeruginosa exposed to 0.82 mM OPP for 20 and 60 minutes. Our data indicated that OPP upregulated the transcription of genes encoding ribosomal, virulence and membrane transport proteins after both treatment times. After 20 minutes of exposure to 0.82 mM OPP, genes involved in the exhibition of swarming motility and anaerobic respiration were upregulated. After 60 minutes of OPP treatment, the transcription of genes involved in amino acid and lipopolysaccharide biosynthesis were upregulated. Further, the transcription of the ribosome modulation factor (rmf and an alternative sigma factor (rpoS of RNA polymerase were downregulated after both treatment times. Conclusion Results from this study indicate that after 20 minutes of exposure to OPP, genes that have been linked to the exhibition of anaerobic respiration and swarming motility were upregulated. This study also suggests that the downregulation of the rmf and rpoS genes may be indicative of the mechanism by which OPP causes decreases in cell viability in P. aeruginosa. Consequently, a protective response involving the upregulation of translation leading to the

  14. Pseudomonas aeruginosa Reduces VX-809 Stimulated F508del-CFTR Chloride Secretion by Airway Epithelial Cells.

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    Bruce A Stanton

    Full Text Available P. aeruginosa is an opportunistic pathogen that chronically infects the lungs of 85% of adult patients with Cystic Fibrosis (CF. Previously, we demonstrated that P. aeruginosa reduced wt-CFTR Cl secretion by airway epithelial cells. Recently, a new investigational drug VX-809 has been shown to increase F508del-CFTR Cl secretion in human bronchial epithelial (HBE cells, and, in combination with VX-770, to increase FEV1 (forced expiratory volume in 1 second by an average of 3-5% in CF patients homozygous for the F508del-CFTR mutation. We propose that P. aeruginosa infection of CF lungs reduces VX-809 + VX-770- stimulated F508del-CFTR Cl secretion, and thereby reduces the clinical efficacy of VX-809 + VX-770.F508del-CFBE cells and primary cultures of CF-HBE cells (F508del/F508del were exposed to VX-809 alone or a combination of VX-809 + VX-770 for 48 hours and the effect of P. aeruginosa on F508del-CFTR Cl secretion was measured in Ussing chambers. The effect of VX-809 on F508del-CFTR abundance was measured by cell surface biotinylation and western blot analysis. PAO1, PA14, PAK and 6 clinical isolates of P. aeruginosa (3 mucoid and 3 non-mucoid significantly reduced drug stimulated F508del-CFTR Cl secretion, and plasma membrane F508del-CFTR.The observation that P. aeruginosa reduces VX-809 and VX-809 + VX-770 stimulated F508del CFTR Cl secretion may explain, in part, why VX-809 + VX-770 has modest efficacy in clinical trials.

  15. Characterization of biofilm-like structures formed by Pseudomonas aeruginosa in a synthetic mucus medium

    Directory of Open Access Journals (Sweden)

    Haley Cecily L

    2012-08-01

    Full Text Available Abstract Background The accumulation of thick stagnant mucus provides a suitable environment for the growth of Pseudomonas aeruginosa and Staphylococcus aureus within the lung alveoli of cystic fibrosis (CF patients. These infections cause significant lung damage, leading to respiratory failure and death. In an artificial mucin containing medium ASM+, P. aeruginosa forms structures that resemble typical biofilms but are not attached to any surface. We refer to these structures as biofilm like structures (BLS. Using ASM+ in a static microtiter plate culture system, we examined the roles of mucin, extracellular DNA, environmental oxygen (EO2, and quorum sensing (QS in the development of biofilm-like structures (BLS by P. aeruginosa; and the effect of EO2 and P. aeruginosa on S. aureus BLS. Results Under 20% EO2, P. aeruginosa strain PAO1 produced BLS that resemble typical biofilms but are confined to the ASM+ and not attached to the surface. Levels of mucin and extracellular DNA within the ASM+ were optimized to produce robust well developed BLS. At 10% EO2, PAO1 produced thicker, more developed BLS, while under 0% EO2, BLS production was diminished. In contrast, the S. aureus strain AH133 produced well-developed BLS only under 20% EO2. In PAO1, loss of the QS system genes rhlI and rhlR affected the formation of BLS in ASM+ in terms of both structure and architecture. Whether co-inoculated into ASM+ with AH133, or added to established AH133 BLS, PAO1 eliminated AH133 within 48–56 h. Conclusions The thick, viscous ASM+, which contains mucin and extracellular DNA levels similar to those found in the CF lung, supports the formation of biofilm-like structures similar to the aggregates described within CF airways. Alterations in environmental conditions or in the QS genes of P. aeruginosa, as occurs naturally during the progression of CF lung infection, affect the architecture and quantitative structural features of these BLS. Thus, ASM+ provides an

  16. Pathogenic bacteria and their drug sensitivity in patients with advanced lung cancer accompanying lung infection%晚期肺癌患者并发肺部感染的病原菌及药敏分析

    Institute of Scientific and Technical Information of China (English)

    于海容; 张丽娜; 薛庆亮; 薛新颖; 王娜; 杨冰; 汪建新

    2012-01-01

    目的 探讨晚期肺癌患者并发肺部感染的病原菌种类及药敏情况.方法 统计我院2009 年3 月-2011 年5 月收治的56 例Ⅳ期肺癌伴肺部感染的患者,对所有患者的痰菌培养及药敏试验结果进行回顾性分析.结果 共分离菌株228 株,其中G- 菌113 株(49.56%),以铜绿假单孢菌占首位(18.86%),其次为鲍曼氏不动杆菌、嗜麦芽窄食单胞菌、肺炎克雷伯杆菌及大肠埃希氏菌等;G+ 菌47 株(20.61%),以凝固酶阴性葡萄球菌为主(10.09%),其次为屎肠球菌、金黄色葡萄球菌等.真菌菌株68 株(29.82%),以白色念珠菌为主(14.04%).G- 菌主要对头孢他啶、氨基糖甙类、碳青酶烯类敏感,G+ 菌主要对万古霉素、替考拉宁、利奈唑胺敏感,真菌主要对氟康唑敏感.结论 晚期肺癌合并肺部感染主要以G- 菌为主,常伴有真菌感染,根据药敏结果合理应用抗生素是治疗的关键.%Objective To study the pathogenic bacteria and their drug sensitivity in patients with advanced lung cancer accompanying lung infection. Methods Sputum culture and drug sensitivity test data about 56 patients with advanced lung cancer accompanying lung infection admitted to our hospital from March 2009 to May 2011 were retrospectively analyzed. Results Two hundred and twenty-eight strains were isolated from sputum. Of these strains,113 (49.56%)were Gram-negative bacteria with Pseudomonas aeruginosa accounted for 18.86% followed by Bowman amobile bacteria, Klebsiella pneumoniae and E.coli, 47(20.61 %)were Gram-positive bacteria with coagulase negative staphylococcus accounted for 10.09% followed by Mycobacterium stercoris and Staphylococcus aureus, 68(29.82%)were fungi with Candida albicans accounted for 14.04%. The Gram-negative bacteria were sensitive to ceftazidime, aminoglycoside and carbapenem. The Gram-positive bacteria were sensitive to vancomycin, teicoplanin and linezolid. Fungi were sensitive to fluconazole. Conclusion Gram

  17. Efficacy comparison of adjuvants in PcrV vaccine against Pseudomonas aeruginosa pneumonia.

    Science.gov (United States)

    Hamaoka, Saeko; Naito, Yoshifumi; Katoh, Hideya; Shimizu, Masaru; Kinoshita, Mao; Akiyama, Koichi; Kainuma, Atsushi; Moriyama, Kiyoshi; Ishii, Ken J; Sawa, Teiji

    2017-02-01

    Vaccination against the type III secretion system of P. aeruginosa is a potential prophylactic strategy for reducing the incidence and improving the poor prognosis of P. aeruginosa pneumonia. In this study, the efficacies of three different adjuvants, Freund's adjuvant (FA), aluminum hydroxide (alum) and CpG oligodeoxynucleotide (ODN), were examined from the viewpoint of inducing PcrV-specific immunity against virulent P. aeruginosa. Mice that had been immunized intraperitoneally with recombinant PcrV formulated with one of the above adjuvants were challenged intratracheally with a lethal dose of P. aeruginosa. The PcrV-FA immunized group attained a survival rate of 91%, whereas the survival rates of the PcrV-alum and PcrV-CpG groups were 73% and 64%, respectively. In terms of hypothermia recovery after bacterial instillation, PcrV-alum was the most protective, followed by PcrV-FA and PcrV-CpG. The lung edema index was lower in the PcrV-CpG vaccination group than in the other groups. PcrV-alum immunization was associated with the greatest decrease in myeloperoxidase in infected lungs, and also decreased the number of lung bacteria to a similar number as in the PcrV-FA group. There was less neutrophil recruitment in the lungs of mice vaccinated with PcrV-alum or PcrV-CpG than in those of mice vaccinated with PcrV-FA or PcrV alone. Overall, in terms of mouse survival the PcrV-CpG vaccine, which could be a relatively safe next-generation vaccine, showed a comparable effect to the PcrV-alum vaccine.

  18. Effects of Pseudomonas aeruginosa on CFTR chloride secretion and the host immune response.

    Science.gov (United States)

    Stanton, Bruce A

    2017-04-01

    In the healthy lung the opportunistic pathogen, Pseudomonas aeruginosa, is rapidly eliminated by mucociliary clearance, a process that is dependent on the activity of the CFTR anion channel that, in concert with a number of other transport proteins, regulates the volume and composition of the periciliary surface liquid. This fluid layer is essential to enable cilia to clear pathogens from the lungs. However, in cystic fibrosis (CF), mutations in the CFTR gene reduce Cl(-) and [Formula: see text] secretion, thereby decreasing periciliary surface liquid volume and mucociliary clearance of bacteria. In CF this leads to persistent infection with the opportunistic pathogen, P. aeruginosa, which is the cause of reduced lung function and death in ~95% of CF patients. Others and we have conducted studies to elucidate the effects of P. aeruginosa on wild-type and Phe508del-CFTR Cl(-) secretion as well as on the host immune response. These studies have demonstrated that Cif (CFTR inhibitory factor), a virulence factor secreted by P. aeruginosa, is associated with reduced lung function in CF and induces the ubiquitination and degradation of wt-CFTR as well as TAP1, which plays a key role in viral and bacterial antigen presentation. Cif also enhances the degradation of Phe508del-CFTR that has been rescued by ORKAMBI, a drug approved for CF patients homozygous for the Phe508del-CFTR mutation, thereby reducing drug efficacy. This review is based on the Hans Ussing Distinguished Lecture at the 2016 Experimental Biology Meeting given by the author.

  19. A case of failed eradication of cystic fibrosis-related sinus colonisation by Pseudomonas aeruginosa.

    LENUS (Irish Health Repository)

    Linnane, Barry

    2015-10-01

    Pseudomonas aeruginosa is a pathogen associated with cystic fibrosis that has potential to decrease lung function and cause respiratory failure. Paranasal sinuses are increasingly recognised as potential reservoirs for intermittent colonisation by P. aeruginosa. This case documents investigation and outcome of P. aeruginosa recurrence in a male paediatric patient over an eight year period.

  20. Immunization protected well nourished mice but not undernourished ones from lung injury in Methicillin-resistant Staphylococcus aureus (MRSA infection

    Directory of Open Access Journals (Sweden)

    da Cunha Maria

    2009-11-01

    Full Text Available Abstract Background Staphylococcus aureus methicillin-resistant (MRSA has been frequently isolated from endotracheal and lung puncture aspirates in malnourished children with pneumonia. In this work we evaluated the susceptibility of undernourished BALB/c mice and its ability to mount a protective immunity against MRSA with emphasis on the lung involvement. Results BALB/c mice submitted to a 20% dietary restriction during 20 days presented a significant decrease in body weight, lymphocyte number and also atrophy in thymus and intestinal epithelium. Determination of bacterial load by the number of colony forming units (CFU indicated a similar susceptibility whereas the findings of Gram stain clearly suggested a higher amount of bacteria in the lungs of normal mice than in the undernourished ones. Immunization reduced bacterial growth in the lungs of normal mice but not in the undernourished ones. Histopathological analysis showed that inflammation appeared in the lungs from normal mice only after infection and that immunization prevented this pulmonary inflammatory process. On the other hand, undernourished mice presented lung inflammation even before infection. In addition, the degree of this inflammatory process did not change with infection or previous immunization. Conclusion Our results indicated that lung injury during MRSA infection is prevented by previous immunization in well nourished but not in undernourished mice.

  1. Drastic Attenuation of Pseudomonas aeruginosa Pathogenicity in a Holoxenic Mouse Experimental Model Induced by Subinhibitory Concentrations of Phenyllactic acid (PLA)

    Science.gov (United States)

    Chifiriuc, Mariana–Carmen; Veronica, Lazar; Dracea, Olguta; Ditu, Lia-Mara; Smarandache, Diana; Bucur, Marcela; Larion, Cristina; Cernat, Ramona; Sasarman, Elena

    2007-01-01

    The discovery of communication systems regulating bacterial virulence has afforded a novel opportunity to control infectious bacteria without interfering with growth. In this paper we describe the effect of subinhibitory concentrations of phenyllactic acid (PLA) on the pathogenicity of Pseudomonas aeruginosa in mice. The animals were inoculated by oral (p.o.), intranasal (i.n.), intravenous (i.v.) and intraperitoneal (i.p.) routes with P. aeruginoasa wild and PLA-treated cultures. The mice were followed up during 16 days after infection and the body weight, mortality and morbidity rate were measured every day. The microbial charge was studied by viable cell counts in lungs, spleen, intestinal mucosa and blood. The mice batches infected with wild P. aeruginosa bacterial cultures exhibited high mortality rates (100 % after i.v. and i.p. route) and very high cell counts in blood, lungs, intestine and spleen. In contrast, the animal batches infected with PLA treated bacterial cultures exhibited good survival rates (0 % mortality) and the viable cell counts in the internal organs revealed with one exception the complete abolition of the invasive capacity of the tested strains. In this study, using a mouse infection model we show that D-3-phenyllactic acid (PLA) can act as a potent antagonist of Pseudomonas (P.) aeruginosa pathogenicity, without interfering with the bacterial growth, as demonstrated by the improvement of the survival rates as well as the clearance of bacterial strains from the body.

  2. Effects of Silver Nanoparticles on Multiple Drug-Resistant Strains of Staphylococcus aureus and Pseudomonas aeruginosa from Mastitis-Infected Goats: An Alternative Approach for Antimicrobial Therapy

    Directory of Open Access Journals (Sweden)

    Yu-Guo Yuan

    2017-03-01

    Full Text Available Recently, silver nanoparticles (AgNPs have been widely used in various applications as antimicrobial agents, anticancer, diagnostics, biomarkers, cell labels, and drug delivery systems for the treatment of various diseases. Microorganisms generally acquire resistance to antibiotics through the course of antibacterial therapy. Multi-drug resistance (MDR has become a growing problem in the treatment of infectious diseases, and the widespread use of broad-spectrum antibiotics has resulted in the development of antibiotic resistance by numerous human and animal bacterial pathogens. As a result, an increasing number of microorganisms are resistant to multiple antibiotics causing continuing economic losses in dairy farming. Therefore, there is an urgent need for the development of alternative, cost-effective, and efficient antimicrobial agents that overcome antimicrobial resistance. Here, AgNPs synthesized using the bio-molecule quercetin were characterized using various analytical techniques. The synthesized AgNPs were highly spherical in shape and had an average size of 11 nm. We evaluated the efficacy of synthesized AgNPs against two MDR pathogenic bacteria, namely, Pseudomonas aeruginosa and Staphylococcus aureus, which were isolated from milk samples produced by mastitis-infected goats. The minimum inhibitory concentrations (MICs of AgNPs against P. aeruginosa and S. aureus were found to be 1 and 2 μg/mL, respectively. Our findings suggest that AgNPs exert antibacterial effects in a dose- and time-dependent manner. Results from the present study demonstrate that the antibacterial activity of AgNPs is due to the generation of reactive oxygen species (ROS, malondialdehyde (MDA, and leakage of proteins and sugars in bacterial cells. Results of the present study showed that AgNP-treated bacteria had significantly lower lactate dehydrogenase activity (LDH and lower adenosine triphosphate (ATP levels compared to the control. Furthermore, Ag

  3. [Molecular typification of Pseudomonas aeruginosa strains isolated from patients with cystic fibrosis].

    Science.gov (United States)

    Iglesias, N G; Marengo, J M; Rentería, F; Gatti, B; Segal, E; Semorile, L

    2008-01-01

    Cystic fibrosis is the most frequent lethal genetic disease that affects the caucasian population. The main cause of morbidity is the chronic lung infection, being the infection caused by Pseudomonas aeruginosa the most difficult to eradicate. This bacteria can be acquired in direct form, by person-to-person transfer, or indirectly, by hospital acquired infection. The Centro Provincial de Referencia de Fibrosis Quistica functioning in the Hospital de Niños "Sor María Ludovica", in La Plata, cares almost 220 patients aged two months to 45 years. The life expectancy depends of factors like the early diagnosis of the disease and the later acquisition of the chronic lung infection. The purpose of this work was the molecular typing of P. aeruginosa isolates obtained from cystic fibrosis patients to evaluate the genomic relationship among them. The study was carried out using RAPD-PCR. The analysis showed a great genetic heterogeneity among the isolates. The separation of the patients in groups in accordance with its bacteriology, that implies the attendance in different days and the implementation of isolation (or segregation) measures had demonstrated to be, in addition to other strategies, effective in the reduction of cross infections.

  4. Exaggerated Acute Lung Injury and Impaired Antibacterial Defenses During Staphylococcus aureus Infection in Rats with the Metabolic Syndrome.

    Directory of Open Access Journals (Sweden)

    Xiaomei Feng

    Full Text Available Rats with Metabolic Syndrome (MetaS have a dysregulated immune response to the aseptic trauma of surgery. We hypothesized that rats with MetaS would have dysregulated inflammation, increased lung injury, and less effective antibacterial defenses during Staphylococcus (S. aureus sepsis as compared to rats without MetaS. Low capacity runner (LCR; a model of MetaS and high capacity runner (HCR rats were challenged intravenously with S. aureus bacteria. After 48 h, inflammatory mediators and bacteria were quantified in the blood, bronchoalveolar lavage fluid (BALF, and lung homogenates. Lungs were analyzed histologically. BALF protein and lung wet-dry ratios were quantified to assess for vascular leak. Endpoints were compared in infected LCR vs HCR rats. LCR rats had higher blood and lung S. aureus counts, as well as higher levels of IL-6 in plasma, lungs and BALF, MIP-2 in plasma and lung, and IL-17A in lungs. Conversely, LCR rats had lower levels of IL-10 in plasma and lungs. Although lactate levels, and liver and renal function tests were similar between groups, LCR rats had higher BALF protein and lung wet-dry ratios, and more pronounced acute lung injury histologically. During S. aureus bacteremia, as compared with HCR rats, LCR (MetaS rats have heightened pro-inflammatory responses, accompanied by increased acute lung injury and vascular leak. Notably, despite an augmented pro-inflammatory phenotype, LCR rats have higher bacterial levels in their blood and lungs. The MetaS state may exacerbate lung injury and vascular leak by attenuating the inflammation-resolving response, and by weakening antimicrobial defenses.

  5. Exaggerated Acute Lung Injury and Impaired Antibacterial Defenses During Staphylococcus aureus Infection in Rats with the Metabolic Syndrome.

    Science.gov (United States)

    Feng, Xiaomei; Maze, Mervyn; Koch, Lauren G; Britton, Steven L; Hellman, Judith

    2015-01-01

    Rats with Metabolic Syndrome (MetaS) have a dysregulated immune response to the aseptic trauma of surgery. We hypothesized that rats with MetaS would have dysregulated inflammation, increased lung injury, and less effective antibacterial defenses during Staphylococcus (S.) aureus sepsis as compared to rats without MetaS. Low capacity runner (LCR; a model of MetaS) and high capacity runner (HCR) rats were challenged intravenously with S. aureus bacteria. After 48 h, inflammatory mediators and bacteria were quantified in the blood, bronchoalveolar lavage fluid (BALF), and lung homogenates. Lungs were analyzed histologically. BALF protein and lung wet-dry ratios were quantified to assess for vascular leak. Endpoints were compared in infected LCR vs HCR rats. LCR rats had higher blood and lung S. aureus counts, as well as higher levels of IL-6 in plasma, lungs and BALF, MIP-2 in plasma and lung, and IL-17A in lungs. Conversely, LCR rats had lower levels of IL-10 in plasma and lungs. Although lactate levels, and liver and renal function tests were similar between groups, LCR rats had higher BALF protein and lung wet-dry ratios, and more pronounced acute lung injury histologically. During S. aureus bacteremia, as compared with HCR rats, LCR (MetaS) rats have heightened pro-inflammatory responses, accompanied by increased acute lung injury and vascular leak. Notably, despite an augmented pro-inflammatory phenotype, LCR rats have higher bacterial levels in their blood and lungs. The MetaS state may exacerbate lung injury and vascular leak by attenuating the inflammation-resolving response, and by weakening antimicrobial defenses.

  6. Synergistic antibacterial efficacy of early combination treatment with tobramycin and quorum-sensing inhibitors against Pseudomonas aeruginosa in an intraperitoneal foreign-body infection mouse model

    DEFF Research Database (Denmark)

    Christensen, Louise; van Gennip, Maria; Jakobsen, Tim H;

    2012-01-01

    Quorum sensing (QS)-deficient Pseudomonas aeruginosa biofilms formed in vitro are more susceptible to tobramycin than QS-proficient P. aeruginosa biofilms, and combination treatment with a QS inhibitor (QSI) and tobramycin shows synergistic effects on the killing of in vitro biofilms. We extended...

  7. Nodular inflammatory foci are sites of T cell priming and control of murine cytomegalovirus infection in the neonatal lung.

    Directory of Open Access Journals (Sweden)

    Felix R Stahl

    Full Text Available Neonates, including mice and humans, are highly susceptible to cytomegalovirus (CMV infection. However, many aspects of neonatal CMV infections such as viral cell tropism, spatio-temporal distribution of the pathogen as well as genesis of antiviral immunity are unknown. With the use of reporter mutants of the murine cytomegalovirus (MCMV we identified the lung as a primary target of mucosal infection in neonatal mice. Comparative analysis of neonatal and adult mice revealed a delayed control of virus replication in the neonatal lung mucosa explaining the pronounced systemic infection and disease in neonates. This phenomenon was supplemented by a delayed expansion of CD8(+ T cell clones recognizing the viral protein M45 in neonates. We detected viral infection at the single-cell level and observed myeloid cells forming "nodular inflammatory foci" (NIF in the neonatal lung. Co-localization of infected cells within NIFs was associated with their disruption and clearance of the infection. By 2-photon microscopy, we characterized how neonatal antigen-presenting cells (APC interacted with T cells and induced mature adaptive immune responses within such NIFs. We thus define NIFs of the neonatal lung as niches for prolonged MCMV replication and T cell priming but also as sites of infection control.

  8. Nodular inflammatory foci are sites of T cell priming and control of murine cytomegalovirus infection in the neonatal lung.

    Science.gov (United States)

    Stahl, Felix R; Heller, Katrin; Halle, Stephan; Keyser, Kirsten A; Busche, Andreas; Marquardt, Anja; Wagner, Karen; Boelter, Jasmin; Bischoff, Yvonne; Kremmer, Elisabeth; Arens, Ramon; Messerle, Martin; Förster, Reinhold

    2013-01-01

    Neonates, including mice and humans, are highly susceptible to cytomegalovirus (CMV) infection. However, many aspects of neonatal CMV infections such as viral cell tropism, spatio-temporal distribution of the pathogen as well as genesis of antiviral immunity are unknown. With the use of reporter mutants of the murine cytomegalovirus (MCMV) we identified the lung as a primary target of mucosal infection in neonatal mice. Comparative analysis of neonatal and adult mice revealed a delayed control of virus replication in the neonatal lung mucosa explaining the pronounced systemic infection and disease in neonates. This phenomenon was supplemented by a delayed expansion of CD8(+) T cell clones recognizing the viral protein M45 in neonates. We detected viral infection at the single-cell level and observed myeloid cells forming "nodular inflammatory foci" (NIF) in the neonatal lung. Co-localization of infected cells within NIFs was associated with their disruption and clearance of the infection. By 2-photon microscopy, we characterized how neonatal antigen-presenting cells (APC) interacted with T cells and induced mature adaptive immune responses within such NIFs. We thus define NIFs of the neonatal lung as niches for prolonged MCMV replication and T cell priming but also as sites of infection control.

  9. 恶性肿瘤患者铜绿假单胞菌血流感染的临床分析%Clinical analysis of cancer patients with Pseudomonas aeruginosa bloodstream infections

    Institute of Scientific and Technical Information of China (English)

    白长森; 李丁; 张文芳; 张青; 郑珊; 张鹏

    2014-01-01

    目的:分析恶性肿瘤患者合并铜绿假单胞菌血流感染的相关危险因素及耐药性情况。方法:回顾性分析天津医科大学肿瘤医院2010年1月至2012年12月30例合并铜绿假单胞菌血流感染及90例无铜绿假单胞菌血流感染的恶性肿瘤患者的临床资料;采用Whonet 5.6软件和SPSS 19.0对数据进行统计学分析。结果:感染组患者男20例,女10例,平均年龄(60.9±11.2)岁;对照组患者男60例,女30例,平均年龄(51.3±15.9)岁;多因素Logistic回归分析显示住院次数、合并其他部位感染和应用≥2种类型抗生素为恶性肿瘤患者合并铜绿假单胞菌血流感染的独立危险因素(P80%)。合并铜绿假单胞菌血流感染的恶性肿瘤患者的死亡率为60%。结论:恶性肿瘤患者合并铜绿假单胞菌血流感染死亡率高,在临床工作中必须采取综合防治的措施,减少铜绿假单胞菌血流感染的发生。%Objective:To analyze risk factors of cancer patients with Pseudomonas aeruginosa bloodstream infections and drug resistance. Methods:Clinical data of 30 cancer patients with P. aeruginosa bloodstream infection and 90 without infection who were ad-mitted in the Tianjin Medical University Cancer Institute and Hospital between January 2010 and December 2012 were retrospectively analyzed. Whonet 5.6 and SPSS19.0 software were used for statistical analysis of the data. Results:The infection group consisted of 20 male and 10 female patients with a mean age of 60.9±11.2 years. The control group consisted of 60 males and 30 females with a mean age of 51.3 ± 15.9 years. Multivariate logistic regression analysis showed that the number of hospitalization, combined with infection of other sites, and more than two types of antibiotics were independent risk factors of cancer patients with P. aeruginosa bloodstream infec-tions. P. aeruginosa showed high sensitivity(>80%) to carbapenems, ceftazidime, cefepime

  10. Treatment of Cytomegalovirus Infection with Cidofovir and CMV Immune Globulin in a Lung Transplant Recipient

    Directory of Open Access Journals (Sweden)

    Heinrike Wilkens

    2016-01-01

    Full Text Available Cytomegalovirus (CMV infection after lung transplantation is associated with increased risk for pneumonitis and bronchiolitis obliterans as well as allograft rejection and opportunistic infections. Ganciclovir is the mainstay of prophylaxis and treatment but CMV infections can be unresponsive. Apart from direct antiviral drugs, CMV immunoglobulin (CMVIG preparations may be considered but are only licensed for prophylaxis. A CMV-seronegative 42-year-old man with cystic fibrosis received a lung from a CMV-seropositive donor. Intravenous ganciclovir prophylaxis was delayed until day 12 due to acute postoperative renal failure and was accompanied by five doses of CMVIG (10 g. By day 16, CMV-DNA was detectable and rising; CMV-specific T-cells were undetectable. Switch from ganciclovir to foscarnet prompted a transient decrease in CMV viral load, but after increasing again to reach 3600 copies/mL foscarnet was changed to intravenous cidofovir and CMVIG was restarted. CMV load continued to fluctuate and declined slowly, whereas CMV-specific T-cells were detected five months later and increased thereafter. At last follow-up, the patient was in very good clinical condition with no evidence of bronchiolitis obliterans. No side effects of this treatment were observed. In this hard-to-treat case, the combination of cidofovir with off-label use of CMVIG contributed to a successful outcome.

  11. The NOD/RIP2 pathway is essential for host defenses against Chlamydophila pneumoniae lung infection.

    Directory of Open Access Journals (Sweden)

    Kenichi Shimada

    2009-04-01

    Full Text Available Here we investigated the role of the Nod/Rip2 pathway in host responses to Chlamydophila pneumoniae-induced pneumonia in mice. Rip2(-/- mice infected with C. pneumoniae exhibited impaired iNOS expression and NO production, and delayed neutrophil recruitment to the lungs. Levels of IL-6 and IFN-gamma levels as well as KC and MIP-2 levels in bronchoalveolar lavage fluid (BALF were significantly decreased in Rip2(-/- mice compared to wild-type (WT mice at day 3. Rip2(-/- mice showed significant delay in bacterial clearance from the lungs and developed more severe and chronic lung inflammation that continued even on day 35 and led to increased mortality, whereas WT mice cleared the bacterial load, recovered from acute pneumonia, and survived. Both Nod1(-/- and Nod2(-/- mice also showed delayed bacterial clearance, suggesting that C. pneumoniae is recognized by both of these intracellular receptors. Bone marrow chimera experiments demonstrated that Rip2 in BM-derived cells rather than non-hematopoietic stromal cells played a key role in host responses in the lungs and clearance of C. pneumoniae. Furthermore, adoptive transfer of WT macrophages intratracheally was able to rescue the bacterial clearance defect in Rip2(-/- mice. These results demonstrate that in addition to the TLR/MyD88 pathway, the Nod/Rip2 signaling pathway also plays a significant role in intracellular recognition, innate immune host responses, and ultimately has a decisive impact on clearance of C. pneumoniae from the lungs and survival of the infectious challenge.

  12. The NOD/RIP2 pathway is essential for host defenses against Chlamydophila pneumoniae lung infection.

    Science.gov (United States)

    Shimada, Kenichi; Chen, Shuang; Dempsey, Paul W; Sorrentino, Rosalinda; Alsabeh, Randa; Slepenkin, Anatoly V; Peterson, Ellena; Doherty, Terence M; Underhill, David; Crother, Timothy R; Arditi, Moshe

    2009-04-01

    Here we investigated the role of the Nod/Rip2 pathway in host responses to Chlamydophila pneumoniae-induced pneumonia in mice. Rip2(-/-) mice infected with C. pneumoniae exhibited impaired iNOS expression and NO production, and delayed neutrophil recruitment to the lungs. Levels of IL-6 and IFN-gamma levels as well as KC and MIP-2 levels in bronchoalveolar lavage fluid (BALF) were significantly decreased in Rip2(-/-) mice compared to wild-type (WT) mice at day 3. Rip2(-/-) mice showed significant delay in bacterial clearance from the lungs and developed more severe and chronic lung inflammation that continued even on day 35 and led to increased mortality, whereas WT mice cleared the bacterial load, recovered from acute pneumonia, and survived. Both Nod1(-/-) and Nod2(-/-) mice also showed delayed bacterial clearance, suggesting that C. pneumoniae is recognized by both of these intracellular receptors. Bone marrow chimera experiments demonstrated that Rip2 in BM-derived cells rather than non-hematopoietic stromal cells played a key role in host responses in the lungs and clearance of C. pneumoniae. Furthermore, adoptive transfer of WT macrophages intratracheally was able to rescue the bacterial clearance defect in Rip2(-/-) mice. These results demonstrate that in addition to the TLR/MyD88 pathway, the Nod/Rip2 signaling pathway also plays a significant role in intracellular recognition, innate immune host responses, and ultimately has a decisive impact on clearance of C. pneumoniae from the lungs and survival of the infectious challenge.

  13. 晚期肺癌肺部感染细菌培养及药敏实验%Experimental study of advanced lung cancer susceptibility lung infection and bacterial culture

    Institute of Scientific and Technical Information of China (English)

    吴展陵; 钟敏华; 谢志斌; 彭清臻

    2016-01-01

    Objective:To explore the advanced lung cancer patients with bacterial lung infection infection and sen-sitivity test status. Methods:All 100 cases were analyzad for bacterial infection and drug resistance. Results:In 100 patients with advanced lung cancer complicated by lung infection culture results:150 samples were isolated patho-gens,gram - negative bacteria 77,the proportion of 51. 3% ,as the first place,followed by fungi 53,the ratio 35. 3% , gram - positive bacteria 20,accounting for the smallest proportion. A larger proportion of gram - negative bacteria were Pseudomonas aeruginosa,Acinetobacter baumannii,Klebsiella pneumoniae and Escherichia coli bacteria. Fungus Can-dida albicans was the largest proportion,followed by tropical rosary bacteria and Candida glabrata. Gram - positive bacteria occupy the largest proportion of Staphylococcus aureus(6. 7% ),by Pseudomonas aeruginosa,Acinetobacter baumannii,Klebsiella pneumoniae,Escherichia coli and Staphylococcus aureus and the main fungal susceptibility was found that different bacterial or fungal resistance to different antibiotics were different. Conclusion:Advanced lung cancer patients with lung infections,gram - negative bacteria proportion occupied first place,followed by fungi,gram -positive bacteria smallest proportion. Drug susceptibility test different bacterial or fungal resistance to different antibi-otics is different.%目的:探究晚期肺癌肺部感染患者的细菌感染及药敏实验情况。方法:选择2013年3月-2014年7月收治的100例晚期肺癌并发肺部感染患者进行药敏实验研究,分析细菌感染以及耐药状况。结果:100例晚期肺癌并发肺部感染患者痰液标本中的细菌培养结果显示,共分离出150株病原菌,革兰氏阴性菌77株,比例51.3%,占据首位,其次是真菌53株,比例35.3%,革兰氏阳性菌20株,占据比例最小。革兰氏阴性菌中比例较大的有铜绿假单胞菌、鲍氏不动杆菌、肺炎

  14. Role of quorum sensing by Pseudomonas aeruginosa in microbial keratitis and cystic fibrosis

    DEFF Research Database (Denmark)

    Willcox, M.D.P.; Zhu, H.; Conibear, T.C.R.

    2008-01-01

    Pseudomonas aeruginosa is a ubiquitous bacterium that causes opportunistic infections in a range of host tissues and organs. Infections by P. aeruginosa are difficult to treat and hence there is interest in the development of effective therapeutics. One of the key mechanisms that P. aeruginosa us...

  15. Azithromycin-Ciprofloxacin-Impregnated Urinary Catheters Avert Bacterial Colonization, Biofilm Formation, and Inflammation in a Murine Model of Foreign-Body-Associated Urinary Tract Infections Caused by Pseudomonas aeruginosa.

    Science.gov (United States)

    Saini, Hina; Vadekeetil, Anitha; Chhibber, Sanjay; Harjai, Kusum

    2017-03-01

    Pseudomonas aeruginosa is a multifaceted pathogen causing a variety of biofilm-mediated infections, including catheter-associated urinary tract infections (CAUTIs). The high prevalence of CAUTIs in hospitals, their clinical manifestations, such as urethritis, cystitis, pyelonephritis, meningitis, urosepsis, and death, and the associated economic challenges underscore the need for management of these infections. Biomaterial modification of urinary catheters with two drugs seems an interesting approach to combat CAUTIs by inhibiting biofilm. Previously, we demonstrated the in vitro efficacy of urinary catheters impregnated with azithromycin (AZM) and ciprofloxacin (CIP) against P. aeruginosa Here, we report how these coated catheters impact the course of CAUTI induced by P. aeruginosa in a murine model. CAUTI was established in female LACA mice with uncoated or AZM-CIP-coated silicone implants in the bladder, followed by transurethral inoculation of 10(8) CFU/ml of biofilm cells of P. aeruginosa PAO1. AZM-CIP-coated implants (i) prevented biofilm formation on the implant's surface (P ≤ 0.01), (ii) restricted bacterial colonization in the bladder and kidney (P < 0.0001), (iii) averted bacteriuria (P < 0.0001), and (iv) exhibited no major histopathological changes for 28 days in comparison to uncoated implants, which showed persistent CAUTI. Antibiotic implants also overcame implant-mediated inflammation, as characterized by trivial levels of inflammatory markers such as malondialdehyde (P < 0.001), myeloperoxidase (P < 0.05), reactive oxygen species (P ≤ 0.001), and reactive nitrogen intermediates (P < 0.01) in comparison to those in uncoated implants. Further, AZM-CIP-coated implants showed immunomodulation by manipulating the release of inflammatory cytokines interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and IL-10 to the benefit of the host. Overall, the study demonstrates long-term in vivo effectiveness of AZM-CIP-impregnated catheters, which may

  16. Lung infection

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930508 Assessment on the epidemiological effi-ciency resulted from case finding and case-treatment of smear positive pulmonary tuberculo-sis.PENG Daping(彭达平),et al.Hunan Anti—Tuberculosis Instit,Changsha,410006.ChinJ Tuberc &.Respir Dis 1993;16(2):85—87.An epidemiological project for discovery andtreatment of sputum (+)pulmonary tuberculouspatients had been carried out during 1988~1990.The patients collected,were as many as 3.1times of those obtained in the five year pre—ap-

  17. Lung infection

    Institute of Scientific and Technical Information of China (English)

    1992-01-01

    920671 Studies of BAL cells during theairborne Klebsiella pneumoniae infectionin immunocompromised mice. ZHU Ben-hong(朱本洪), et al. Dept Respir Med, XinhuaHosp, Shanghai 2nd Med Univ, 200092. Chin JTuberc & Respir Dis 1992; 15(3): 161-162. We compared immunocompromised mice

  18. Inactivation of the potent Pseudomonas aeruginosa cytotoxin pyocyanin by airway peroxidases and nitrite.

    Science.gov (United States)

    Reszka, Krzysztof J; Xiong, Ye; Sallans, Larry; Pasula, Rajamouli; Olakanmi, Oyebode; Hassett, Daniel J; Britigan, Bradley E

    2012-05-15

    Pyocyanin (1-hydroxy-N-methylphenazine, PCN) is a cytotoxic pigment and virulence factor secreted by the human bacterial pathogen, Pseudomonas aeruginosa. Here, we report that exposure of PCN to airway peroxidases, hydrogen peroxide (H(2)O(2)), and NaNO(2) generates unique mononitrated PCN metabolites (N-PCN) as revealed by HPLC/mass spectrometry analyses. N-PCN, in contrast to PCN, was devoid of antibiotic activity and failed to kill Escherichia coli and Staphylococcus aureus. Furthermore, in contrast to PCN, intratracheal instillation of N-PCN into murine lungs failed to induce a significant inflammatory response. Surprisingly, at a pH of ∼7, N-PCN was more reactive than PCN with respect to NADH oxidation but resulted in a similar magnitude of superoxide production as detected by electron paramagnetic resonance and spin trapping experiments. When incubated with Escherichia coli or lung A549 cells, PCN and N-PCN both led to superoxide formation, but lesser amounts were detected with N-PCN. Our results demonstrate that PCN that has been nitrated by peroxidase/H(2)O(2)/NO(2)(-) systems possesses less cytotoxic/proinflammatory activity than native PCN. Yield of N-PCN was decreased by the presence of the competing physiological peroxidase substrates (thiocyonate) SCN(-) (myeloperoxidase, MPO, and lactoperoxidase, LPO) and Cl(-) (MPO), which with Cl(-) yielded chlorinated PCNs. These reaction products also showed decreased proinflammatory ability when instilled into the lungs of mice. These observations add important insights into the complexity of the pathogenesis of lung injury associated with Pseudomonas aeruginosa infections and provide additional rationale for exploring the efficacy of NO(2)(-) in the therapy of chronic Pseudomonas aeruginosa airway infection in cystic fibrosis.

  19. Mortality associated with Acinetobacter baumannii infections experienced by lung transplant recipients.

    Science.gov (United States)

    Nunley, D R; Bauldoff, G S; Mangino, J E; Pope-Harman, A L

    2010-10-01

    Lung transplantation (LTX) requires continual systemic immunosuppression, which can result in infections that may compromise recipient survival. A recent outbreak of Acinetobacter baumannii at our institution resulted in infections experienced in both LTX recipients and nontransplant patients. A retrospective review was conducted of patients who had A. baumannii recovered from blood, other normally sterile body fluids, and/or respiratory secretions and who had clinical follow-up extending to 1 year postinfection. A. baumannii was considered "multidrug-resistant" when its growth was not inhibited by minimum inhibitory concentrations of multiple antibiotics. Despite the resistance profile, patients were treated with a combination of antibiotics, which included tigecycline, colistimethate, and when susceptible, imipenem. Once infection was diagnosed, immunosuppression was reduced in all LTX recipients. Six LTX recipients became infected with A. baumannii and were contrasted to infections identified in 14 non-LTX, nonimmunosuppressed patients. A. baumannii was persistently recovered in 4 of 6 LTX recipients (66.7%) compared with only 1 of 14 (7.1%) non-LTX patients (χ(2) = 9.9, p = 0.005). LTX recipients received antibiotic therapy for an average of 76 ± 18.4 days compared with 16.0 ± 6.8 days for the non-LTX patients (p = 0.025, Mann-Whitney U test). All 4 of the 6 (66.7%) LTX recipients died as a consequence of their infection compared with 1 of 14 (7.1%) of the non-LTX patients (χ(2) = 9.9, p = 0.005). Despite receiving more antibiotic therapy, LTX recipients who were infected with multidrug-resistant A. baumannii were less likely to clear their infection and experienced greater mortality compared with non-LTX patients.

  20. Dermal Wound Transcriptomic Responses to Infection with Pseudomonas aeruginosa versus Klebsiella pneumoniae in a Rabbit Ear Wound Model

    Science.gov (United States)

    2014-05-02

    syndrome toxin 1. Infect lrnrnun 2005, 73:2164 2174. 65. Narasimhan J, Staschke KA, Wek RC: Dimerization is required for activation of eiF2 kinase Gcn2 in...145 154. 67. Papa FR: Endoplasmic reticulum stress, pancreatic beta cell degeneration, and diabetes. Cold Spring Harbor perspectives In medlcile 2012

  1. Flagellin stimulates protective lung mucosal immunity: role of cathelicidin-related antimicrobial peptide.

    Science.gov (United States)

    Yu, Fu-shin; Cornicelli, Matthew D; Kovach, Melissa A; Newstead, Michael W; Zeng, Xianying; Kumar, Ashok; Gao, Nan; Yoon, Sang Gi; Gallo, Richard L; Standiford, Theodore J

    2010-07-15

    TLRs are required for generation of protective lung mucosal immune responses against microbial pathogens. In this study, we evaluated the effect of the TLR5 ligand flagellin on stimulation of antibacterial mucosal immunity in a lethal murine Pseudomonas aeruginosa pneumonia model. The intranasal pretreatment of mice with purified P. aeruginosa flagellin induced strong protection against intratracheal P. aeruginosa-induced lethality, which was attributable to markedly improved bacterial clearance, reduced dissemination, and decreased alveolar permeability. The protective effects of flagellin on survival required TLR5 and were observed even in the absence of neutrophils. Flagellin induced strong induction of innate genes, most notably the antimicrobial peptide cathelicidin-related antimicrobial peptide. Finally, flagellin-induced protection was partially abrogated in cathelicidin-related antimicrobial peptide-deficient mice. Our findings illustrate the profound stimulatory effect of flagellin on lung mucosal innate immunity, a response that might be exploited therapeutically to prevent the development of gram-negative bacterial infection of the respiratory tract.

  2. Tobramycin inhalation powder: an efficient and efficacious therapy for the treatment of Pseudomonas aeruginosa infection in cystic fibrosis.

    Science.gov (United States)

    Somayaji, Ranjani; Parkins, Michael D

    2015-02-01

    Inhaled antipseudomonal therapies are critical components in the management of cystic fibrosis (CF) and have significantly contributed to improved patient outcomes. Dry powder inhaler technologies represent a significant advance in drug delivery, alleviating treatment burden and potentially improving adherence associated with traditional CF nebulized therapies. Tobramycin inhalation powder (TIP) uses PulmoSphere(®) technology for very efficient drug delivery into the lower airways. In placebo-controlled and comparative studies with traditional tobramycin formulations, TIP is equally efficacious and is associated with increased patient convenience and satisfaction. TIP has been recommended in the 2013 CF Foundation and the 2014 European guidelines as a therapy in CF for the maintenance of lung health. Going forward, TIP may offer a therapeutic advantage over traditional formulations of tobramycin as recent prospective 'real world' studies of TIP have demonstrated high patient tolerance and improved adherence compared with traditional formulations.

  3. Morphology and Morphometry of the Lung in Corn Snakes (Pantherophis guttatus) Infected with Three Different Strains of Ferlavirus.

    Science.gov (United States)

    Starck, J M; Neul, A; Schmidt, V; Kolb, T; Franz-Guess, S; Balcecean, D; Pees, M

    2017-03-08

    Ophidian paramyxovirus (ferlavirus) is a global threat to reptilian sauropsids in herpetological collections, with occasional but fatal effects. This study characterizes the effects of three different genetic strains of ferlavirus on the dynamic changes of histology and morphometry of the lung of corn snakes (Pantherophis guttatus). Lungs from 42 corn snakes were either sham-infected or infected experimentally under standardized conditions. From 4 to 49 days after intratracheal inoculation, the lungs were examined qualitatively and quantitatively. Progressive microscopical changes were seen in the lung. Initially, increased numbers of heterophils were observed in the interstitium followed by proliferation and vacuolation of epithelial cells lining faveoli. Electron microscopy revealed loss of type-I pneumocytes, hyperplasia of type-II pneumocytes, and interstitial infiltrates of heterophils and mononuclear cells. With progression of disease the respiratory epithelium was initially overgrown by transformed type-II pneumocytes and later became multilayered. The results of the study suggest that the respiratory capacity of the lungs declines with disease development. The dynamics of disease development and histopathology differed in snakes infected with different ferlavirus genogroups. Animals infected with virus genogroup B developed histopathological changes and morphometric changes more rapidly and of greater intensity than snakes infected with viruses from genogroups A or C.

  4. Influenza H5N1 virus infection of polarized human alveolar epithelial cells and lung microvascular endothelial cells

    Directory of Open Access Journals (Sweden)

    Yuen Kit M

    2009-10-01

    Full Text Available Abstract Background Highly pathogenic avian influenza (HPAI H5N1 virus is entrenched in poultry in Asia and Africa and continues to infect humans zoonotically causing acute respiratory disease syndrome and death. There is evidence that the virus may sometimes spread beyond respiratory tract to cause disseminated infection. The primary target cell for HPAI H5N1 virus in human lung is the alveolar epithelial cell. Alveolar epithelium and its adjacent lung microvascular endothelium form host barriers to the initiation of infection and dissemination of influenza H5N1 infection in humans. These are polarized cells and the polarity of influenza virus entry and egress as well as the secretion of cytokines and chemokines from the virus infected cells are likely to be central to the pathogenesis of human H5N1 disease. Aim To study influenza A (H5N1 virus replication and host innate immune responses in polarized primary human alveolar epithelial cells and lung microvascular endothelial cells and its relevance to the pathogenesis of human H5N1 disease. Methods We use an in vitro model of polarized primary human alveolar epithelial cells and lung microvascular endothelial cells grown in transwell culture inserts to compare infection with influenza A subtype H1N1 and H5N1 viruses via the apical or basolateral surfaces. Results We demonstrate that both influenza H1N1 and H5N1 viruses efficiently infect alveolar epithelial cells from both apical and basolateral surface of the epithelium but release of newly formed virus is mainly from the apical side of the epithelium. In contrast, influenza H5N1 virus, but not H1N1 virus, efficiently infected polarized microvascular endothelial cells from both apical and basolateral aspects. This provides a mechanistic explanation for how H5N1 virus may infect the lung from systemic circulation. Epidemiological evidence has implicated ingestion of virus-contaminated foods as the source of infection in some instances and our

  5. Dynamics of Pseudomonas aeruginosa genome evolution

    OpenAIRE

    Mathee, Kalai; Narasimhan, Giri; Valdes, Camilo; Qiu, Xiaoyun; Matewish, Jody M.; Koehrsen, Michael; Rokas, Antonis; Yandava, Chandri N.; Engels, Reinhard; Zeng, Erliang; Olavarietta, Raquel; Doud, Melissa; Smith, Roger S.; Montgomery, Philip; White, Jared R.

    2008-01-01

    One of the hallmarks of the Gram-negative bacterium Pseudomonas aeruginosa is its ability to thrive in diverse environments that includes humans with a variety of debilitating diseases or immune deficiencies. Here we report the complete sequence and comparative analysis of the genomes of two representative P. aeruginosa strains isolated from cystic fibrosis (CF) patients whose genetic disorder predisposes them to infections by this pathogen. The comparison of the genomes of the two CF strains...

  6. Soluble CD163 Predicts Incident Chronic Lung, Kidney and Liver Disease in HIV Infection

    DEFF Research Database (Denmark)

    Kirkegaard-Klitbo, Ditte M.; Mejer, Niels; Knudsen, Troels Bygum

    2017-01-01

    OBJECTIVE:: To examine if monocyte and macrophage activity may be on the mechanistic pathway to non-AIDS comorbidity by investigating the associations between plasma soluble CD163 (sCD163) and incident non-AIDS comorbidities in well-treated HIV-infected individuals. DESIGN:: Prospective single......-center cohort study. METHODS:: Plasma sCD163 was quantified by ELISA technique at study entry in 2004/05 and non-AIDS comorbidity was identified by International Classification of Disease Tenth revision (ICD-10) diagnosis codes and registry linkage in 2014/2015. Associations between sCD163 and incident...... comorbidity was examined using multivariable Cox proportional hazards models adjusted for pertinent covariates. RESULTS:: In HIV-1 infected individuals (n=799), the highest quartile of plasma sCD163 was associated with incident chronic lung disease (adjusted hazard ratio (aHR), 3.2; 95% confidence interval...

  7. Qingfei Xiaoyan Wan, a traditional Chinese medicine formula, ameliorates Pseudomonas aeruginosa-induced acute lung inflammation by regulation of PI3K/AKT and Ras/MAPK pathways.

    Science.gov (United States)

    Hou, Yuanyuan; Nie, Yan; Cheng, Binfeng; Tao, Jin; Ma, Xiaoyao; Jiang, Min; Gao, Jie; Bai, Gang

    2016-05-01

    Gram-negative pathogen-induced nosocomial infections and resistance are a most serious menace to global public health. Qingfei Xiaoyan Wan (QF), a traditional Chinese medicine (TCM) formula, has been used clinically in China for the treatment of upper respiratory tract infections, acute or chronic bronchitis and pulmonary infection. In this study, the effects of QF on Pseudomonas aeruginosa-induced acute pneumonia in mice were evaluated. The mechanisms by which four typical anti-inflammatory ingredients from QF, arctigenin (ATG), cholic acid (CLA), chlorogenic acid (CGA) and sinapic acid (SPA), regulate anti-inflammatory signaling pathways and related targets were investigated using molecular biology and molecular docking techniques. The results showed that pretreatment with QF significantly inhibits the release of cytokines (TNF-α and IL-6) and chemokines (IL-8 and RANTES), reduces leukocytes recruitment into inflamed tissues and ameliorates pulmonary edema and necrosis. In addition, ATG was identified as the primary anti-inflammatory agent with action on the PI3K/AKT and Ras/MAPK pathways. CLA and CGA enhanced the actions of ATG and exhibited synergistic NF-κB inactivation effects possibly via the Ras/MAPK signaling pathway. Moreover, CLA is speculated to target FGFR and MEK firstly. Overall, QF regulated the PI3K/AKT and Ras/MAPK pathways to inhibit pathogenic bacterial infections effectively.

  8. The aliphatic amidase AmiE is involved in regulation of Pseudomonas aeruginosa virulence

    Science.gov (United States)

    Clamens, Thomas; Rosay, Thibaut; Crépin, Alexandre; Grandjean, Teddy; Kentache, Takfarinas; Hardouin, Julie; Bortolotti, Perrine; Neidig, Anke; Mooij, Marlies; Hillion, Mélanie; Vieillard, Julien; Cosette, Pascal; Overhage, Joerg; O’Gara, Fergal; Bouffartigues, Emeline; Dufour, Alain; Chevalier, Sylvie; Guery, Benoit; Cornelis, Pierre; Feuilloley, Marc G. J.; Lesouhaitier, Olivier

    2017-01-01

    We have previously shown that the eukaryotic C-type natriuretic peptide hormone (CNP) regulates Pseudomonas aeruginosa virulence and biofilm formation after binding on the AmiC sensor, triggering the amiE transcription. Herein, the involvement of the aliphatic amidase AmiE in P. aeruginosa virulence regulation has been investigated. The proteome analysis of an AmiE over-producing strain (AmiE+) revealed an expression change for 138 proteins, including some that are involved in motility, synthesis of quorum sensing compounds and virulence regulation. We observed that the AmiE+ strain produced less biofilm compared to the wild type, and over-produced rhamnolipids. In the same line, AmiE is involved in P. aeruginosa motilities (swarming and twitching) and production of the quorum sensing molecules N-acyl homoserine lactones and Pseudomonas Quinolone Signal (PQS). We observed that AmiE overproduction reduced levels of HCN and pyocyanin causing a decreased virulence in different hosts (i.e. Dictyostelium discoideum and Caenorhabditis elegans). This phenotype was further confirmed in a mouse model of acute lung infection, in which AmiE overproduction resulted in an almost fully virulence decrease. Taken together, our data suggest that, in addition to its role in bacterial secondary metabolism, AmiE is involved in P. aeruginosa virulence regulation by modulating pilus synthesis and cell-to-cell communication. PMID:28117457

  9. Use of an artificial neural network to predict risk factors of nosocomial infection in lung cancer patients.

    Science.gov (United States)

    Chen, Jie; Pan, Qin-Shi; Hong, Wan-Dong; Pan, Jingye; Zhang, Wen-Hui; Xu, Gang; Wang, Yu-Min

    2014-01-01

    Statistical methods to analyze and predict the related risk factors of nosocomial infection in lung cancer patients are various, but the results are inconsistent. A total of 609 patients with lung cancer were enrolled to allow factor comparison using Student's t-test or the Mann-Whitney test or the Chi-square test. Variables that were significantly related to the presence of nosocomial infection were selected as candidates for input into the final ANN model. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the performance of the artificial neural network (ANN) model and logistic regression (LR) model. The prevalence of nosocomial infection from lung cancer in this entire study population was 20.1% (165/609), nosocomial infections occurring in sputum specimens (85.5%), followed by blood (6.73%), urine (6.0%) and pleural effusions (1.82%). It was shown that long term hospitalization (≥ 22 days, P= 0.000), poor clinical stage (IIIb and IV stage, P=0.002), older age (≥ 61 year old, P=0.023), and use the hormones were linked to nosocomial infection and the ANN model consisted of these four factors .The artificial neural network model with variables consisting of age, clinical stage, time of hospitalization, and use of hormones should be useful for predicting nosocomial infection in lung cancer cases.

  10. 秀丽隐杆线虫-耐药铜绿假单胞菌感染模型的建立%Establishment of an infection model using Caenorhabditis elegans-multidrug resistance P.aeruginosa

    Institute of Scientific and Technical Information of China (English)

    周雨朦; 陈代杰; 李继安; 邵雷; 朱春宝

    2011-01-01

    目的 建立耐药铜绿假单胞菌感染的秀丽隐杆线虫感染模型。方法 利用临床分离的P.aeruginosa A258制各BHI、PGS、NG和Aga线虫感染平板。采用不同浓度的四环素、利福平和多粘菌素B对感染线虫进行治疗,考察感染线虫的存活率。结果 不同感染平板对线虫致死情况不同。采用NG感染平板对glp-4;sek-1线虫进行感染,其LT50 为3.5d。32μg/mL利福平和16μg/mL多粘菌素B对该感染线虫进行治疗,与不加入药物的对照组相比,其存活率分别提高了5和14倍。但一定浓度的四环素没有提高感染线虫的存活率,在线虫体内不能抑制P.aeruginosa A258的感染,与体外抑菌实验结果相一致。结论 建立了秀丽隐杆线虫-耐药铜绿假单胞菌A258感染模型,为此模型用于抗感染化合物的筛选奠定基础。%Objective Establishment of an infection model using Caenorhabditis elegans-multidrug resistance P. Aeruginosa system. Method P. Aeruginosa A258 strain isolated from clinical patient was used to prepare BHI, PGS, NG and Agar plates for infecting Caenorhabditis elegans. The infected worms were then treated by tetracycline, rifampicin and polymyxin B at different concentrations to investigate the survival rates of infected worms. Results Different infective plates led to different patterns on the worm death. The LT50 was 3.5 days, when glp-4;sek-l mutant worms were transferred to NG medium. Comparing to control groups without antibiotic, the survival rates of infected worms which were treated with 32μg/mL rifampicin and 16ug/mL polymyxin B were increased to 5 and 14 folds. However, tetracycline which was not active against P. Aeruginosa A258 in vitro, and did not promote survival of infected worms. Conclusion We had established the infection model of C. Elegans-multidrug resistance P. Aeruginosa A258, and the model may build the basic of screening anti-infective compounds.

  11. Lung fluke (Paragonimus africanus) infects Nigerian red-capped mangabeys and causes respiratory disease.

    Science.gov (United States)

    Friant, Sagan; Brown, Kelsey; Saari, Mason T; Segel, Nicholas H; Slezak, Julia; Goldberg, Tony L

    2015-12-01

    Eggs of the lung fluke genus Paragonimus were detected in red-capped mangabeys (Cercocebus torquatus) in Nigeria. We assess the role of these primates as potential sylvatic hosts and the clinical effects of the parasite on monkeys. DNA sequenced from eggs in feces were 100% identical in the ITS2 region to Paragonimus africanus sequences from humans in Cameroon. Paragonimus-positive monkeys coughed more than uninfected monkeys. Experimental de-worming led to reduction in parasite intensity and a corresponding reduction of coughing to baseline levels in infected monkeys. This report provides the first evidence of Paragonimus sp. in C. torquatus, of P. africanus in Nigerian wildlife, and the first molecular evidence of the parasite in African wildlife. Coughing, sometimes interpreted as a communication behavior in primates, can actually indicate infection with lung parasites. Observations of coughing in primates may, in turn, provide a useful mechanism for surveillance of Paragonimus spp, which are re-emerging human pathogens, in wildlife reservoirs.

  12. Lung fluke (Paragonimus africanus infects Nigerian red-capped mangabeys and causes respiratory disease

    Directory of Open Access Journals (Sweden)

    Sagan Friant

    2015-12-01

    Full Text Available Eggs of the lung fluke genus Paragonimus were detected in red-capped mangabeys (Cercocebus torquatus in Nigeria. We assess the role of these primates as potential sylvatic hosts and the clinical effects of the parasite on monkeys. DNA sequenced from eggs in feces were 100% identical in the ITS2 region to Paragonimus africanus sequences from humans in Cameroon. Paragonimus-positive monkeys coughed more than uninfected monkeys. Experimental de-worming led to reduction in parasite intensity and a corresponding reduction of coughing to baseline levels in infected monkeys. This report provides the first evidence of Paragonimus sp. in C. torquatus, of P. africanus in Nigerian wildlife, and the first molecular evidence of the parasite in African wildlife. Coughing, sometimes interpreted as a communication behavior in primates, can actually indicate infection with lung parasites. Observations of coughing in primates may, in turn, provide a useful mechanism for surveillance of Paragonimus spp, which are re-emerging human pathogens, in wildlife reservoirs.

  13. Natural killer cells regulate Th1/Treg and Th17/Treg balance in chlamydial lung infection.

    Science.gov (United States)

    Li, Jing; Dong, Xiaojing; Zhao, Lei; Wang, Xiao; Wang, Yan; Yang, Xi; Wang, Hong; Zhao, Weiming

    2016-07-01

    Natural killer (NK) cell is an important component in innate immunity, playing a critical role in bridging innate and adaptive immunity by modulating the function of other immune cells including T cells. In this study, we focused on the role of NK cells in regulating Th1/Treg and Th17/Treg balance during chlamydial lung infection. We found that NK cell-depleted mice showed decreased Th1 and Th17 cells, which was correlated with reduced interferon-γ, interleukin (IL)-12, IL-17 and IL-22 production as well as T-bet and receptor-related orphan receptor gamma t expression compared with mice treated with the isotype control antibody. In contrast, NK cell depletion significantly increased Treg in cell number and related transcription factor (Foxp3) expression. The opposite trends of changes of Th1/Th17 and Treg led to significant reduction in the Th1/Treg and Th17/Treg ratios. The data implicate that NK cells play an important role in host defence against chlamydial lung infection, mainly through maintaining Th1/Treg and Th17/Treg balance.

  14. Leukotriene B4 induces release of antimicrobial peptides in lungs of virally infected mice.

    Science.gov (United States)

    Gaudreault, Eric; Gosselin, Jean

    2008-05-01

    Leukotriene B(4) (LTB(4)) is a lipid mediator of inflammation that was recently shown to exert antiviral activities. In this study, we demonstrate that the release of antimicrobial proteins by neutrophils contribute to an early host defense against influenza virus infection in vitro as well as in vivo. Daily i.v. treatments with LTB(4) lead to a significant decrease in lung viral loads at day 5 postinfection in mice infected with influenza A virus compared with the placebo-treated group. This reduction in viral load was not present in mice deficient in the high-affinity LTB(4) receptor. Viral clearance in lungs was associated with up-regulated presence of antimicrobial peptides such as beta-defensin-3, members of the mouse eosinophil-related RNase family, and the mouse cathelicidin-related antimicrobial peptide. Our results also indicate that neutrophils are important in the antiviral effect of LTB(4). Viral loads in neutrophil-depleted mice were not diminished by LTB(4) administration, and a substantial reduction in the presence of murine cathelicidin-related antimicrobial peptide and the murine eosinophil-related RNase family in lung tissue was observed. Moreover, in vitro treatment of human neutrophil cultures with LTB(4) led rapidly to the secretion of the human cathelicidin LL-37 and eosinophil-derived neurotoxin, known as antiviral peptides. Pretreatment of cell cultures with specific LTB(4) receptor antagonists clearly demonstrate the implication of the high-affinity LTB(4) receptor in the LTB(4)-mediated activity. Together, these results demonstrate the importance of neutrophils and the secretion of antimicrobial peptides during the early immune response mediated by LTB(4) against a viral pathogen.

  15. Vaccination promotes TH1-like inflammation and survival in chronic Pseudomonas aeruginosa pneumonia in rats

    DEFF Research Database (Denmark)

    Johansen, H K; Hougen, H P; Cryz, S J;

    1995-01-01

    In a rat model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis (CF) we studied whether the inflammatory response could be altered by vaccination. Rats were immunized with either a depolymerized alginate toxin A conjugate (D-ALG toxin A), purified alginate, an O...... with the other three groups (p = 0.009). The histopathologic response in the control rats was dominated by numerous polymorphonuclear leukocytes (PMN) surrounding the alginate beads. In contrast, the histopathologic response in rats immunized with D-ALG toxin A changed within the first week after challenge from...

  16. Pharmacokinetic/pharmacodynamic evaluation of sulbactam against Acinetobacter baumannii in in vitro and murine thigh and lung infection models.

    Science.gov (United States)

    Yokoyama, Yuta; Matsumoto, Kazuaki; Ikawa, Kazuro; Watanabe, Erika; Shigemi, Akari; Umezaki, Yasuhiro; Nakamura, Koyo; Ueno, Keiichiro; Morikawa, Norifumi; Takeda, Yasuo

    2014-06-01

    Acinetobacter baumannii is a pathogen that has become globally associated with nosocomial infections. Sulbactam, a potent inhibitor of β-lactamases, was previously shown to be active against A. baumannii strains in vitro and effective against A. baumannii infections. However, a pharmacokinetic/pharmacodynamic (PK/PD) analysis of sulbactam against A. baumannii infections has not yet been performed. This is necessary because optimisation of dosing regimens should be based on PK/PD analysis. Therefore, in vitro and in vivo PK/PD analyses of sulbactam were performed using murine thigh and lung infection models of A. baumannii to evaluate the pharmacokinetics and pharmacodynamics of sulbactam. Sulbactam showed time-dependent bactericidal activity in vitro against A. baumannii. The PK/PD index that best correlated with its in vivo effects was the time that the free drug concentration remained above the minimum inhibitory concentration (fT>MIC) both in the thigh (R(2)=0.95) and lung (R(2)=0.96) infection models. Values of fT>MIC for a static effect and 1, 2 and 3log10 kill, respectively, were 21.0%, 32.9%, 43.6% and 57.3% in the thigh infection model and 20.4%, 24.5%, 29.3% and 37.3% in the lung infection model. Here we report the in vitro and in vivo time-dependent activities of sulbactam against A. baumannii infection and demonstrate that sulbactam was sufficiently bactericidal when an fT>MIC of >60% against A. baumannii thigh infection and >40% against A. baumannii lung infection was achieved.

  17. Efficacy of calcium-EDTA as an inhibitor for metallo-β-lactamase in a mouse model of Pseudomonas aeruginosa pneumonia.

    Science.gov (United States)

    Aoki, Nobumasa; Ishii, Yoshikazu; Tateda, Kazuhiro; Saga, Tomoo; Kimura, Soichiro; Kikuchi, Yoshiaki; Kobayashi, Tetsuo; Tanabe, Yoshinari; Tsukada, Hiroki; Gejyo, Fumitake; Yamaguchi, Keizo

    2010-11-01

    In this study, we have evaluated the efficacy of calcium-EDTA (Ca-EDTA) as an inhibitor of bacterial metalloenzymes, such as metallo-β-lactamase (MBL) and other proteases, in a mouse model of Pseudomonas aeruginosa pneumonia. The simultaneous presence of Ca-EDTA (32 μg/ml) reduced the MICs of imipenem (IPM) in all MBL-producing P. aeruginosa isolates (IMP-1, -2, -7, and -10 and VIM-2) but not non-MBL-producing strains. In the pneumonia model, mice were intranasally infected with MBL-producing P. aeruginosa and then kept under conditions of hyperoxia to mimic ventilator-associated pneumonia. With both intranasal and subcutaneous administrations, Ca-EDTA significantly potentiated survival benefits of IPM compared to those of IPM alone. Ca-EDTA combination therapy induced a significant reduction of the bacterial burden in the lungs (P EDTA against MBL activity was confirmed by using the purified IMP-1 enzyme, which was characterized by a 50% inhibitory concentration (IC(50)) of 55 ± 8.2 μM. Finally, the protective effects of Ca-EDTA were demonstrated by culture supernatant-induced epithelial cell damage and acute lung injury in mice. These data suggest the therapeutic potential of Ca-EDTA not only by the blocking of MBLs but also by neutralizing tissue-damaging metalloproteases in P. aeruginosa infections.

  18. Are ciprofloxacin dosage regimens adequate for antimicrobial efficacy and prevention of resistance? Pseudomonas aeruginosa bloodstream infection in elderly patients as a simulation case study.

    Science.gov (United States)

    Cazaubon, Yoann; Bourguignon, Laurent; Goutelle, Sylvain; Martin, Olivier; Maire, Pascal; Ducher, Michel

    2015-12-01

    The aim of this work was to define the optimal dosage (OD) of ciprofloxacin in order to prevent the emergence of bacterial resistance of Pseudomonas aeruginosa in a geriatric population with a bloodstream infection. A thousand pharmacokinetic profiles were simulated with a ciprofloxacin pharmacokinetic model from the literature. Three dosing regimens were tested for five days: once daily (QD), twice daily (BID), and thrice daily (TID). First of all, effective dosages (ED) of ciprofloxacin were defined as those achieving a target AUC24 /MIC ≥ 125. Then, these ED were simulated in order to calculate the percentage of time spent within the mutant selection window (TMSW ) and to select optimal dosage (OD) defined as those achieving TMSW ≤ 20%. Based on the AUC24 /MIC, for low MICs (0.125 μg/mL), all dosing regimens recommended by French guidelines were effective. For intermediate MICs (0.25 and 0.5 μg/mL), simulated doses higher than those recommended were needed to achieve the efficacy target. About prevention of resistance for low MICs, dosages recommended were only effective in patients with creatinine clearance (CLCR ) ≥ 60 mL/min. For intermediate MICs, dosages higher than recommended were needed to achieve the optimality target. This study shows that current ciprofloxacin dosing guidelines have not been optimized to prevent the emergence of bacterial resistance, especially in geriatric patients with mild to severe renal impairment. To achieve both efficacy and prevention of resistance, ciprofloxacin dosages greater than those recommended would be needed. Tolerance of such higher doses needs to be evaluated in clinical studies.

  19. Plasminogen activator inhibitor-1 in cigarette smoke exposure and influenza A virus infection-induced lung injury.

    Directory of Open Access Journals (Sweden)

    Yashodhar P Bhandary

    Full Text Available Parenchymal lung inflammation and airway and alveolar epithelial cell apoptosis are associated with cigarette smoke exposure (CSE, which contributes to chronic obstructive pulmonary disease (COPD. Epidemiological studies indicate that people exposed to chronic cigarette smoke with or without COPD are more susceptible to influenza A virus (IAV infection. We found increased p53, PAI-1 and apoptosis in AECs, with accumulation of macrophages and neutrophils in the lungs of patients with COPD. In Wild-type (WT mice with passive CSE (PCSE, p53 and PAI-1 expression and apoptosis were increased in AECs as was lung inflammation, while those lacking p53 or PAI-1 resisted AEC apoptosis and lung inflammation. Further, inhibition of p53-mediated induction of PAI-1 by treatment of WT mice with caveolin-1 scaffolding domain peptide (CSP reduced PCSE-induced lung inflammation and reversed PCSE-induced suppression of eosinophil-associated RNase1 (EAR1. Competitive inhibition of the p53-PAI-1 mRNA interaction by expressing p53-binding 3'UTR sequences of PAI-1 mRNA likewise suppressed CS-induced PAI-1 and AEC apoptosis and restored EAR1 expression. Consistent with PCSE-induced lung injury, IAV infection increased p53, PAI-1 and apoptosis in AECs in association with pulmonary inflammation. Lung inflammation induced by PCSE was worsened by subsequent exposure to IAV. Mice lacking PAI-1 that were exposed to IAV showed minimal viral burden based on M2 antigen and hemagglutination analyses, whereas transgenic mice that overexpress PAI-1 without PCSE showed increased M2 antigen and inflammation after IAV infection. These observations indicate that increased PAI-1 expression promotes AEC apoptosis and exacerbates lung inflammation induced by IAV following PCSE.

  20. Acanthamoeba infection in lungs of mice expressed by toll-like receptors (TLR2 and TLR4).

    Science.gov (United States)

    Derda, Monika; Wojtkowiak-Giera, Agnieszka; Kolasa-Wołosiuk, Agnieszka; Kosik-Bogacka, Danuta; Hadaś, Edward; Jagodziński, Paweł P; Wandurska-Nowak, Elżbieta

    2016-06-01

    Toll-like receptors (TLRs) play a key role in the innate immune responses to a variety of pathogens including parasites. TLRs are among the most highly conserved in the evolution of the receptor family, localized mainly on cells of the immune system and on other cells such as lung cells. The aim of this study was to determine for the first time the expression of TLR2 and TLR4 in the lung of Acanthamoeba spp. infected mice using quantitative real-time polymerase chain reaction (Q-PCR) and immunohistochemical (IHC) staining. The Acanthamoeba spp. were isolated from a patient with Acanthamoeba keratitis (AK) (strain Ac 55) and from environmental samples of water from Malta Lake (Poznań, Poland - strain Ac 43). We observed a significantly increased level of expression of TLR2 as well as TLR4 mRNA from 2 to 30 days post Acanthamoeba infection (dpi) in the lungs of mice infected with Ac55 (KP120880) and Ac43 (KP120879) strains. According to our observations, increased TLR2 and TLR4 expression in the pneumocytes, interstitial cells and epithelial cells of the bronchial tree may suggest an important role of these receptors in protective immunity against Acanthamoeba infection in the lung. Moreover, increased levels of TLR2 and TLR4 mRNA expression in infected Acanthamoeba mice may suggest the involvement of these TLRs in the recognition of this amoeba pathogen-associated molecular pattern (PAMP).

  1. Simultaneous sinus and lung infections in patients with primary ciliary dyskinesia

    DEFF Research Database (Denmark)

    Alanin, Mikkel Christian; Johansen, Helle Krogh; Aanaes, Kasper

    2015-01-01

    Conclusion: The sinuses should be considered as a bacterial reservoir and a target for surgery and antibiotic treatment in patients with primary ciliary dyskinesia (PCD). The observed decrease in serum precipitating antibodies (precipitins) against Pseudomonas aeruginosa may indicate a beneficial...

  2. In utero infection with PRRS virus modulates cellular functions of blood monocytes and alveolar lung macrophages in piglets

    DEFF Research Database (Denmark)

    Riber, Ulla; Nielsen, Jens; Lind, Peter

    2004-01-01

    . Phagocytic capacity of blood monocytes against Salmonella bacteria was investigated by flow cytometry. Oxidative burst in blood monocytes and in alveolar lung macrophages was investigated by luminol- and lucigenin-enhanced chemiluminescence, respectively. Decreased phagocytosis against Salmonella was found...... burst capacity of alveolar lung macrophages was decreased, especially in 2- and 4-week-old piglets, compared to age-matched control piglets. The present results indicate that in utero infection with PRRSV inhibits phagocytosis against Salmonella in blood monocytes as well as the oxidative burst capacity...... in blood monocytes from 4- and 6-week-old infected piglets compared to controls. In contrast, 2-week-old infected piglets showed phagocytic responses comparable to age matched control piglets. While oxidative burst capacity was increased in blood (PBMC) from in utero PRRSV infected piglets, the oxidative...

  3. Integrated analysis of microRNA expression and mRNA transcriptome in lungs of avian influenza virus infected broilers

    Directory of Open Access Journals (Sweden)

    Wang Ying

    2012-06-01

    Full Text Available Abstract Background Avian influenza virus (AIV outbreaks are worldwide threats to both poultry and humans. Our previous study suggested microRNAs (miRNAs play significant roles in the regulation of host response to AIV infection in layer chickens. The objective of this study was to test the hypothesis if genetic background play essential role in the miRNA regulation of AIV infection in chickens and if miRNAs that were differentially expressed in layer with AIV infection would be modulated the same way in broiler chickens. Furthermore, by integrating with parallel mRNA expression profiling, potential molecular mechanisms of host response to AIV infection can be further exploited. Results Total RNA isolated from the lungs of non-infected and low pathogenic H5N3 infected broilers at four days post-infection were used for both miRNA deep sequencing and mRNA microarray analyses. A total of 2.6 M and 3.3 M filtered high quality reads were obtained from infected and non-infected chickens by Solexa GA-I Sequencer, respectively. A total of 271 miRNAs in miRBase 16.0 were identified and one potential novel miRNA was discovered. There were 121 miRNAs differentially expressed at the 5% false discovery rate by Fisher’s exact test. More miRNAs were highly expressed in infected lungs (108 than in non-infected lungs (13, which was opposite to the findings in layer chickens. This result suggested that a different regulatory mechanism of host response to AIV infection mediated by miRNAs might exist in broiler chickens. Analysis using the chicken 44 K Agilent microarray indicated that 508 mRNAs (347 down-regulated were differentially expressed following AIV infection. Conclusions A comprehensive analysis combining both miRNA and targeted mRNA gene expression suggests that gga-miR-34a, 122–1, 122–2, 146a, 155, 206, 1719, 1594, 1599 and 451, and MX1, IL-8, IRF-7, TNFRS19 are strong candidate miRNAs or genes involved in regulating the host response to AIV

  4. Detection of P. aeruginosa harboring bla CTX-M-2, bla GES-1 and bla GES-5, bla IMP-1 and bla SPM-1 causing infections in Brazilian tertiary-care hospital

    Directory of Open Access Journals (Sweden)

    Polotto Milena

    2012-08-01

    Full Text Available Abstract Background Nosocomial infections caused by Pseudomonas aeruginosa presenting resistance to beta-lactam drugs are one of the most challenging targets for antimicrobial therapy, leading to substantial increase in mortality rates in hospitals worldwide. In this context, P. aeruginosa harboring acquired mechanisms of resistance, such as production of metallo-beta-lactamase (MBLs and extended-spectrum beta-lactamases (ESBLs have the highest clinical impact. Hence, this study was designed to investigate the presence of genes codifying for MBLs and ESBLs among carbapenem resistant P. aeruginosa isolated in a Brazilian 720-bed teaching tertiary care hospital. Methods Fifty-six carbapenem-resistant P. aeruginosa strains were evaluated for the presence of MBL and ESBL genes. Strains presenting MBL and/or ESBL genes were submitted to pulsed-field gel electrophoresis for genetic similarity evaluation. Results Despite the carbapenem resistance, genes for MBLs (blaSPM-1 or blaIMP-1 were detected in only 26.7% of isolates. Genes encoding ESBLs were detected in 23.2% of isolates. The blaCTX-M-2 was the most prevalent ESBL gene (19.6%, followed by blaGES-1 and blaGES-5 detected in one isolate each. In all isolates presenting MBL phenotype by double-disc synergy test (DDST, the blaSPM-1 or blaIMP-1 genes were detected. In addition, blaIMP-1 was also detected in three isolates which did not display any MBL phenotype. These isolates also presented the blaCTX-M-2 gene. The co-existence of blaCTX-M-2 with blaIMP-1 is presently reported for the first time, as like as co-existence of blaGES-1 with blaIMP-1. Conclusions In this study MBLs production was not the major mechanism of resistance to carbapenems, suggesting the occurrence of multidrug efflux pumps, reduction in porin channels and production of other beta-lactamases. The detection of blaCTX-M-2,blaGES-1 and blaGES-5 reflects the recent emergence of ESBLs among antimicrobial resistant P. aeruginosa and

  5. CXCR3 Directs Antigen-Specific Effector CD4+ T Cell Migration to the Lung During Parainfluenza Virus Infection

    DEFF Research Database (Denmark)

    Kohlmeier, Jacob E; Cookenham, Tres; Miller, Shannon C;

    2009-01-01

    effector CD4(+) T cell migration to the lungs. To assess the role of CCR5 and CXCR3 in vivo, we directly compared the migration of Ag-specific wild-type and chemokine receptor-deficient effector T cells in mixed bone marrow chimeric mice during a parainfluenza virus infection. CXCR3-deficient effector CD4......Effector T cells are a crucial component of the adaptive immune response to respiratory virus infections. Although it was previously reported that the chemokine receptors CCR5 and CXCR3 affect trafficking of respiratory virus-specific CD8(+) T cells, it is unclear whether these receptors govern......(+) T cells were 5- to 10-fold less efficient at migrating to the lung compared with wild-type cells, whereas CCR5-deficient effector T cells were not impaired in their migration to the lung. In contrast to its role in trafficking, CXCR3 had no impact on effector CD4(+) T cell proliferation, phenotype...

  6. Positively charged biopolymeric nanoparticles for the inhibition of Pseudomonas aeruginosa biofilms

    Science.gov (United States)

    Chronopoulou, Laura; Di Domenico, Enea Gino; Ascenzioni, Fiorentina; Palocci, Cleofe

    2016-10-01

    Currently, many microbial infections have the potential to become lethal owing to the development of antimicrobial resistance by means of different mechanisms and mainly on the basis of the fact that many drugs are unable to reach therapeutic levels in the target sites. This requires the use of high doses and frequent administrations, causing adverse side effects or in some cases toxicity. The use of nanoparticle systems could help overcome such problems and increase drug efficacy. In the present study, we developed a new drug delivery system based on the use of biopolymeric nanovectors loaded with tobramycin (Tb), which is the standard antibiotic for the treatment of Cystic Fibrosis-associated P. aeruginosa lung infections. Tb-loaded biopolymeric nanoparticles composed by dextran sulfate (DS) and chitosan (CS) were prepared by ionotropic gelation. We optimized drug entrapment in DS/CS nanoparticles, obtaining particles of 170 nm and with a drug loading of 400 µg Tb/mg of nanoparticles. In accord with in vitro release experiments, such preparations were able to release approximately 25 % of their cargo in 60 h. In vitro, the antimicrobial efficacy of the drug delivery system on P. aeruginosa biofilm was tested and compared to the effects of free drug revealing that this formulation can reduce the viability of P. aeruginosa biofilms for 48 h with a single-dose administration.

  7. Emergence of carbapenem resistance due to the novel insertion sequence ISPa8 in Pseudomonas aeruginosa.

    Directory of Open Access Journals (Sweden)

    Randal C Fowler

    Full Text Available Chronic lung infections due to the persistence of Pseudomonas aeruginosa in cystic fibrosis patients are typically associated with the emergence of antibiotic resistance. The purpose of this study was to investigate the mechanisms responsible for the emergence of carbapenem resistance when a clinical isolate of P. aeruginosa collected from a patient with cystic fibrosis was challenged with meropenem. Nine carbapenem-resistant mutants were selected with subinhibitory concentrations of meropenem from a clinical isolate of P. aeruginosa and characterized for carbapenem resistance. Increased carbapenem MICs were associated with the identification of the novel insertion sequence ISPa8 within oprD or its promoter region in all the mutants. The position of ISPa8 was different for each of the mutants evaluated. In addition, Southern blot analyses identified multiple copies of ISPa8 within the genomes of the mutants and their parent isolate. These data demonstrate that transposition of IS elements within the Pseudomonas genome can influence antibiotic susceptibility. Understanding the selective pressures associated with the emergence of antibiotic resistance is critical for the judicious use of antimicrobial chemotherapy and the successful treatment of bacterial infections.

  8. Emergence of carbapenem resistance due to the novel insertion sequence ISPa8 in Pseudomonas aeruginosa.

    Science.gov (United States)

    Fowler, Randal C; Hanson, Nancy D

    2014-01-01

    Chronic lung infections due to the persistence of Pseudomonas aeruginosa in cystic fibrosis patients are typically associated with the emergence of antibiotic resistance. The purpose of this study was to investigate the mechanisms responsible for the emergence of carbapenem resistance when a clinical isolate of P. aeruginosa collected from a patient with cystic fibrosis was challenged with meropenem. Nine carbapenem-resistant mutants were selected with subinhibitory concentrations of meropenem from a clinical isolate of P. aeruginosa and characterized for carbapenem resistance. Increased carbapenem MICs were associated with the identification of the novel insertion sequence ISPa8 within oprD or its promoter region in all the mutants. The position of ISPa8 was different for each of the mutants evaluated. In addition, Southern blot analyses identified multiple copies of ISPa8 within the genomes of the mutants and their parent isolate. These data demonstrate that transposition of IS elements within the Pseudomonas genome can influence antibiotic susceptibility. Understanding the selective pressures associated with the emergence of antibiotic resistance is critical for the judicious use of antimicrobial chemotherapy and the successful treatment of bacterial infections.

  9. Nocardia kroppenstedtii sp. nov., an actinomycete isolated from a lung transplant patient with a pulmonary infection.

    LENUS (Irish Health Repository)

    Jones, Amanda L

    2014-03-01

    A novel actinomycete, strain N1286(T), isolated from a lung transplant patient with a pulmonary infection, was provisionally assigned to the genus Nocardia. The strain had chemotaxonomic and morphological properties typical of members of the genus Nocardia and formed a distinct phyletic line in the Nocardia 16S rRNA gene tree. Isolate N1286(T) was most closely related to Nocardia farcinica DSM 43665(T) (99.8% gene sequence similarity) but could be distinguished from the latter by the low level of DNA-DNA relatedness. These strains were also distinguishable on the basis of a broad range of phenotypic properties. It is concluded that strain N1286(T) represents a novel species of the genus Nocardia for which the name Nocardia kroppenstedtii sp. nov. is proposed. The type strain is N1286(T) ( = DSM 45810(T) = NCTC 13617(T)).

  10. Trip to immunity: resistant cytomegalovirus infection in a lung transplant recipient

    Directory of Open Access Journals (Sweden)

    Nikolaus Kneidinger

    2014-11-01

    Full Text Available We report the case of a young female lung transplant recipient with difficult-to-treat cytomegalovirus (CMV disease. While treatment with intravenous (IV ganciclovir failed due to antiviral drug resistance, a trial with foscarnet resulted in severe side effects. In addition, the patient received IV CMV-specific immune globulins as adjunctive therapy and leflunomide as experimental therapy. In this context, CMV-specific immune monitoring was performed and was successfully implemented in management decisions. The patient was screened for acquisition of an adaptive immune response, and antiviral prophylaxis and therapy was tailored according to results. This report highlights the impact of CMV-specific immune monitoring on individualized therapy for appropriate prophylaxis and management of CMV infection and diseases.

  11. Immuno PET/MR imaging allows specific detection of Aspergillus fumigatus lung infection in vivo

    DEFF Research Database (Denmark)

    Rolle, Anna-Maria; Hasenberg, Mike; Thornton, Christopher R.;

    2016-01-01

    Invasive pulmonary aspergillosis (IPA) is a life-threatening lung disease caused by the fungus Aspergillus fumigatus, and is a leading cause of invasive fungal infection-related mortality and morbidity in patients with hematological malignancies and bone marrow transplants. We developed and teste...

  12. Evaluation of combination therapy for Burkholderia cenocepacia lung infection in different in vitro and in vivo models

    Science.gov (United States)

    Brackman, Gilles; Crabbé, Aurélie; Rigole, Petra; Vercruysse, Jurgen; Verstraete, Glenn; Cappoen, Davie; Vervaet, Chris; Cos, Paul

    2017-01-01

    Burkholderia cenocepacia is an opportunistic pathogen responsible for life-threatening infections in cystic fibrosis patients. B. cenocepacia is extremely resistant towards antibiotics and therapy is complicated by its ability to form biofilms. We investigated the efficacy of an alternative antimicrobial strategy for B. cenocepacia lung infections using in vitro and in vivo models. A screening of the NIH Clinical Collection 1&2 was performed against B. cenocepacia biofilms formed in 96-well microtiter plates in the presence of tobramycin to identify repurposing candidates with potentiator activity. The efficacy of selected hits was evaluated in a three-dimensional (3D) organotypic human lung epithelial cell culture model. The in vivo effect was evaluated in the invertebrate Galleria mellonella and in a murine B. cenocepacia lung infection model. The screening resulted in 60 hits that potentiated the activity of tobramycin against B. cenocepacia biofilms, including four imidazoles of which econazole and miconazole were selected for further investigation. However, a potentiator effect was not observed in the 3D organotypic human lung epithelial cell culture model. Combination treatment was also not able to increase survival of infected G. mellonella. Also in mice, there was no added value for the combination treatment. Although potentiators of tobramycin with activity against biofilms of B. cenocepacia were identified in a repurposing screen, the in vitro activity could not be confirmed nor in a more sophisticated in vitro model, neither in vivo. This stresses the importance of validating hits resulting from in vitro studies in physiologically relevant model systems. PMID:28248999

  13. Functional genomics highlights differential induction of antiviral pathways in the lungs of SARS-CoV-infected macaques.

    NARCIS (Netherlands)

    A. de Lang (Anna); T. Baas (Tracey); T.H. Teal (Thomas); L.M.E. Leijten (Lonneke); B. Rain (Brandon); A.D.M.E. Osterhaus (Albert); B.L. Haagmans (Bart); M.G. Katze (Michael)

    2007-01-01

    textabstractThe pathogenesis of severe acute respiratory syndrome coronavirus (SARS-CoV) is likely mediated by disproportional immune responses and the ability of the virus to circumvent innate immunity. Using functional genomics, we analyzed early host responses to SARS-CoV infection in the lungs o

  14. Evidence of airborne excretion of Pneumocystis carinii during infection in immunocompetent rats. Lung involvement and antibody response.

    Directory of Open Access Journals (Sweden)

    Jean Menotti

    Full Text Available To better understand the role of immunocompetent hosts in the diffusion of Pneumocystis in the environment, airborne shedding of Pneumocystis carinii in the surrounding air of experimentally infected Sprague Dawley rats was quantified by means of a real-time PCR assay, in parallel with the kinetics of P. carinii loads in lungs and specific serum antibody titres. Pneumocystis-free Sprague Dawley rats were intratracheally inoculated at day 0 (d0 and then followed for 60 days. P. carinii DNA was detected in lungs until d29 in two separate experiments and thereafter remained undetectable. A transient air excretion of Pneumocystis DNA was observed between d14 and d22 in the first experiment and between d9 and d19 in the second experiment; it was related to the peak of infection in lungs. IgM and IgG anti-P. carinii antibody increase preceded clearance of P. carinii in the lungs and cessation of airborne excretion. In rats receiving a second challenge 3 months after the first inoculation, Pneumocystis was only detected at a low level in the lungs of 2 of 3 rats at d2 post challenge and was never detected in air samples. Anti-Pneumocystis antibody determinations showed a typical secondary IgG antibody response. This study provides the first direct evidence that immunocompetent hosts can excrete Pneumocystis following a primary acquired infection. Lung infection was apparently controlled by the immune response since fungal burdens decreased to become undetectable as specific antibodies reached high titres in serum. This immune response was apparently protective against reinfection 3 months later.

  15. 多药耐药铜绿假单胞菌医院感染的高危因素及药物敏感性分析%High risk factors of nosocomial infection caused by multidrug-resistant Pseudomonas aeruginosa and analysis of drug sensitivity

    Institute of Scientific and Technical Information of China (English)

    曹利君; 王春萍

    2011-01-01

    OBJECTIVE To investigate the risk factors for nosocomial infection caused by multidrug-resistant Pseudomonas aeruginosa and analyze the drug sensitivity. METHODS A total of 98 cases of patients with P. Aeruginosa infection in our hospital from Jan 2007 to May 2011 were selected in this study and divided them into control group (sensitive group) with 48 cases and observation group (multi-drug resistant group) with 50 patients. The age, length of stay, mechanical ventilation rate associated with lung-based diseases, APACHE TJ score and so on for the two groups were compared, and statistics and analysis for the observation group of departments and MIC distribution were performed. RESULTS The age of the observed group (60. 25±5. 66)years was older than the control group (53. 14±6. 13)years, length of stay (35. 28±6. 89)d was longer than the control group (26. 52±6. 37)d, mechanical ventilation rate (50. 0%) was higher than control group (25. 0%) , associated with lung disease (28.0%) was proportion (12. 5%} higher than the control group, APACHE II score (20. 5± 3.1) points was (15. 4i2, 9) points higher than the control group. The highest proportion in distributed departments were ICU and neurology, and they were 24. 0% and 20. 0% respectively, There were significantly different (P<0. 05). CONCLUSION There are characteristics of the nosocomial infection in risk factors and drug sensitivity of multi-drug resistant P. Aeruginosa, which are is worthy of the attention in clinic.%目的 探讨分析多药耐药性铜绿假单胞菌医院感染的高危因素及药物敏感性.方法 选取2007年1月-2011年5月检测出的98例铜绿假单胞菌感染患者为研究对象,将其分为对照组(敏感组)48例和观察组(多药耐药组)50例,对两组年龄、住院时间、机械通气率、伴有肺部基础疾病、APACHEⅡ评分等进行统计及比较,并对观察组的科室分布及MIC进行统计及分析.结果 观察组平均年龄(60.25±5.66)

  16. Silver against Pseudomonas aeruginosa biofilms

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas; Kirketerp-Møller, K.; Kristiansen, S.

    2007-01-01

    Silver has been recognized for its antimicrobial properties for centuries. Most studies on the antibacterial efficacy of silver, with particular emphasis on wound healing, have been performed on planktonic bacteria. Our recent studies, however, strongly suggest that colonization of wounds involves...... bacteria in both the planktonic and biofilm modes of growth. The action of silver on mature in vitro biofilms of Pseudomonas aeruginosa, a primary pathogen of chronic infected wounds, was investigated. The results show that silver is very effective against mature biofilms of P. aeruginosa......, but that the silver concentration is important. A concentration of 5-10 ig/mL silver sulfadiazine eradicated the biofilm whereas a lower concentration (1 ig/mL) had no effect. The bactericidal concentration of silver required to eradicate the bacterial biofilm was 10-100 times higher than that used to eradicate...

  17. Mycobacterium tuberculosis can gain access to adipose depots of mice infected via the intra-nasal route and to lungs of mice with an infected subcutaneous fat implant.

    Science.gov (United States)

    Agarwal, Pooja; Pandey, Praveen; Sarkar, Jayanta; Krishnan, Manju Y

    2016-04-01

    Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis has the remarkable ability to persist as non-replicating forms in the host. These persisters are tolerant to drugs targeting actively replicating bacilli and hence are responsible for the need of an extended duration of anti-tubercular therapy. The anatomical locations and cell types housing Mtb persisters are being investigated in the recent times. Adipose tissue and the adipocytes are proposed niches of Mtb persisters. In the present study, we carried out experiments in the immunocompetent Swiss mice to see the dissemination of Mtb from lungs to adipose tissue and vice versa. Mice infected intra-nasally with ∼ 10(6), 10(4) or 10(2) bacilli harboured Mtb in various adipose depots distal to the lungs such as the visceral, subcutaneous and peri-renal depots. The dissemination was minimal at two weeks post-infection, as evident from culture negative adipose tissue samples. But at seven weeks post-infection, viable Mtb could be detected in 78%, 66% and 66% of the samples from high, moderate and low dose-infection groups respectively. In a separate experiment, Mtb-infected pre-adipocytes were implanted subcutaneously to un-infected mice. At five weeks post-implantation, the intact implants had a mean 7 ± 0.53 log10 CFUs/100 mg tissue, while the lungs had a mean 3.25 ± 0.32 log10 CFUs/100 mg tissue. In conclusion, the study shows that Mtb can disseminate from lungs to distant adipose depots and vice versa.

  18. Influenza A Virus Infection in Pigs Attracts Multifunctional and Cross-Reactive T Cells to the Lung

    Science.gov (United States)

    Talker, Stephanie C.; Stadler, Maria; Koinig, Hanna C.; Mair, Kerstin H.; Rodríguez-Gómez, Irene M.; Graage, Robert; Zell, Roland; Dürrwald, Ralf; Starick, Elke; Harder, Timm; Weissenböck, Herbert; Lamp, Benjamin; Hammer, Sabine E.; Ladinig, Andrea; Saalmüller, Armin

    2016-01-01

    ABSTRACT Pigs are natural hosts for influenza A viruses and play a critical role in influenza epidemiology. However, little is known about their influenza-evoked T-cell response. We performed a thorough analysis of both the local and systemic T-cell response in influenza virus-infected pigs, addressing kinetics and phenotype as well as multifunctionality (gamma interferon [IFN-γ], tumor necrosis factor alpha [TNF-α], and interleukin-2 [IL-2]) and cross-reactivity. A total of 31 pigs were intratracheally infected with an H1N2 swine influenza A virus (FLUAVsw) and consecutively euthanized. Lungs, tracheobronchial lymph nodes, and blood were sampled during the first 15 days postinfection (p.i.) and at 6 weeks p.i. Ex vivo flow cytometry of lung lymphocytes revealed an increase in proliferating (Ki-67+) CD8+ T cells with an early effector phenotype (perforin+ CD27+) at day 6 p.i. Low frequencies of influenza virus-specific IFN-γ-producing CD4+ and CD8+ T cells could be detected in the lung as early as 4 days p.i. On consecutive days, influenza virus-specific CD4+ and CD8+ T cells produced mainly IFN-γ and/or TNF-α, reaching peak frequencies around day 9 p.i., which were up to 30-fold higher in the lung than in tracheobronchial lymph nodes or blood. At 6 weeks p.i., CD4+ and CD8+ memory T cells had accumulated in lung tissue. These cells showed diverse cytokine profiles and in vitro reactivity against heterologous influenza virus strains, all of which supports their potential to combat heterologous influenza virus infections in pigs. IMPORTANCE Pigs not only are a suitable large-animal model for human influenza virus infection and vaccine development but also play a central role in the emergence of new pandemic strains. Although promising candidate universal vaccines are tested in pigs and local T cells are the major correlate of heterologous control, detailed and targeted analyses of T-cell responses at the site of infection are scarce. With the present study, we

  19. 一起疑似铜绿假单胞菌医院感染暴发的调查%SURVEY ON A SUSPECTED OUTBREAK OF Pseudomonas aeruginosa INFECTION IN HOSPI-TAL

    Institute of Scientific and Technical Information of China (English)

    王文娟; 邓文琳

    2014-01-01

    Objective To know a suspected outbreak of Pseudomonas aeruginosa infection in hospital,and to provide ev-idence for controlling the spread of infection through investigation.Methods Field surveys and epidemiological case -control study methods were used to study and analysis of hospital infection cases,and then to provide interventions.Results Seven cases Pseudomonas aeruginosa infections continuously occurred in thoracic surgical ICU within 20 days.Pseudo-monas aeruginosa were separated from the patient′s sputum,while the homology Pseudomonas aeruginosa were separated in the ward and on the hands of medical personnel.With two or more underlying diseases,ventilator,central venous catheter and long-term use of antibiotics were the main risk factors for the infection.The infection was timely controlled by taking active treatment and effective disinfection and isolation measures.Conclusion This is a hospital infection outbreak event which has been effectively controlled by taking active intervening measures caused by Pseudomonas aeruginosa in thoracic surgical ICU.%目的:了解一起疑似铜绿假单胞菌引起的医院感染暴发事件,为控制其感染蔓延提供依据。方法采用现场流行病学调查和病例对照研究的方法,对此次医院感染病例进行研究与分析,提出综合干预措施。结果该医院胸外科ICU在20日之内连续发生7例铜绿假单胞菌感染患者,从患者的痰标本中培养出铜绿假单胞菌,同时在该病房环境和医务人员手上检出同源铜绿假单胞菌。患有两种及以上基础疾病、使用呼吸机、中心静脉置管和长期大量使用抗菌药物是本次感染的主要危险因素。经采取积极救治和有效的消毒隔离措施,及时控制了疫情的发展。结论该医院胸外科ICU铜绿假单胞菌引起住院患儿感染为一起医院感染暴发,经采取有效的控制措施控制了疫情。

  20. Tetrahydrodipicolinate N-succinyltransferase and dihydrodipicolinate synthase from Pseudomonas aeruginosa: structure analysis and gene deletion.

    Directory of Open Access Journals (Sweden)

    Robert Schnell

    Full Text Available The diaminopimelic acid pathway of lysine biosynthesis has been suggested to provide attractive targets for the development of novel antibacterial drugs. Here we report the characterization of two enzymes from this pathway in the human pathogen Pseudomonas aeruginosa, utilizing structural biology, biochemistry and genetics. We show that tetrahydrodipicolinate N-succinyltransferase (DapD from P. aeruginosa is specific for the L-stereoisomer of the amino substrate L-2-aminopimelate, and its D-enantiomer acts as a weak inhibitor. The crystal structures of this enzyme with L-2-aminopimelate and D-2-aminopimelate, respectively, reveal that both compounds bind at the same site of the enzyme. Comparison of the binding interactions of these ligands in the enzyme active site suggests misalignment of the amino group of D-2-aminopimelate for nucleophilic attack on the succinate moiety of the co-substrate succinyl-CoA as the structural basis of specificity and inhibition. P. aeruginosa mutants where the dapA gene had been deleted were viable and able to grow in a mouse lung infection model, suggesting that DapA is not an optimal target for drug development against this organism. Structure-based sequence alignments, based on the DapA crystal structure determined to 1.6 Å resolution revealed the presence of two homologues, PA0223 and PA4188, in P. aeruginosa that could substitute for DapA in the P. aeruginosa PAO1ΔdapA mutant. In vitro experiments using recombinant PA0223 protein could however not detect any DapA activity.

  1. Effect of lung resection and sham surgery on the frequency of infection in alloxan-diabetic rats

    Directory of Open Access Journals (Sweden)

    A.C. Seidel

    2003-03-01

    Full Text Available The present study was carried out in order to determine the effect of lung resection on the frequency of infections in alloxan-diabetic rats. Adult female Wistar rats were injected with alloxan (40 mg/kg, iv to induce diabetes mellitus (group D; N = 45 or with vehicle (1.0 ml/kg, iv to be used as controls (group C; N = 45. Thirty-six days after receiving alloxan both groups were randomly divided into three subgroups: no operation (NO; N = 15, sham operation (SO; N = 15, and left pneumonectomy (PE; N = 15. The rats were sacrificed 36 days after surgery and their lungs were examined microscopically and macroscopically. The occurrence of thoracic wall infection, thoracic wall abscess, lung abscess and pleural empyema was similar in groups D and C. In contrast, the overall infection rate was higher (P<0.05 in the diabetic rats (SO-D and PE-D subgroups, but not in the NO-D subgroup. Considering that the overall infection rate was similar in the SO-D and PE-D subgroups, we suggest that surgery but not pneumonectomy was related to the higher prevalence of infection in diabetic rats.

  2. Perinatal Exposure to Insecticide Methamidophos Suppressed Production of Proinflammatory Cytokines Responding to Virus Infection in Lung Tissues in Mice

    Directory of Open Access Journals (Sweden)

    Wataru Watanabe

    2013-01-01

    Full Text Available Methamidophos, a representative organophosphate insecticide, is regulated because of its severe neurotoxicity, but it is suspected of contaminating agricultural foods in many countries due to illicit use. To reveal unknown effects of methamidophos on human health, we evaluated the developmental immunotoxicity of methamidophos using a respiratory syncytial virus (RSV infection mouse model. Pregnant mice were exposed to methamidophos (10 or 20 ppm in their drinking water from gestation day 10 to weaning on postnatal day 21. Offsprings born to these dams were intranasally infected with RSV. The levels of interleukin-6 (IL-6 and interferon-gamma in the bronchoalveolar lavage fluids after infection were significantly decreased in offspring mice exposed to methamidophos. Treatment with methamidophos did not affect the pulmonary viral titers but suppressed moderately the inflammation of lung tissues of RSV-infected offspring, histopathologically. DNA microarray analysis revealed that gene expression of the cytokines in the lungs of offspring mice exposed to 20 ppm of methamidophos was apparently suppressed compared with the control. Methamidophos did not suppress IL-6 production in RSV-infected J774.1 cell cultures. Thus, exposure of the mother to methamidophos during pregnancy and nursing was suggested to cause an irregular immune response in the lung tissues in the offspring mice.

  3. Intensive-care unit lung infections: The role of imaging with special emphasis on multi-detector row computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Romano, Luigia; Pinto, Antonio; Merola, Stefanella; Gagliardi, Nicola; Tortora, Giovanni [Department of Diagnostic Imaging, Cardarelli Hospital, Naples Italy-Via G. Merliani 31, 80127 Naples (Italy); Scaglione, Mariano [Department of Diagnostic Imaging, Cardarelli Hospital, Naples Italy-Via G. Merliani 31, 80127 Naples (Italy)], E-mail: mscaglione@tiscali.it

    2008-03-15

    Nosocomial pneumonia is the most frequent hospital-acquired infection. In mechanically ventilated patients admitted to an intensive-care unit as many as 7-41% may develop pneumonia. The role of imaging is to identify the presence, location and extent of pulmonary infection and the presence of complications. However, the poor resolution of bedside plain film frequently limits the value of radiography as an accurate diagnostic tool. To date, multi-detector row computed tomography with its excellent contrast resolution is the most sensitive modality for evaluating lung parenchyma infections.

  4. The Lon protease is essential for full virulence in Pseudomonas aeruginosa.

    Science.gov (United States)

    Breidenstein, Elena B M; Janot, Laure; Strehmel, Janine; Fernandez, Lucia; Taylor, Patrick K; Kukavica-Ibrulj, Irena; Gellatly, Shaan L; Levesque, Roger C; Overhage, Joerg; Hancock, Robert E W

    2012-01-01

    Pseudomonas aeruginosa PAO1 lon mutants are supersusceptible to ciprofloxacin, and exhibit a defect in cell division and in virulence-related properties, such as swarming, twitching and biofilm formation, despite the fact that the Lon protease is not a traditional regulator. Here we set out to investigate the influence of a lon mutation in a series of infection models. It was demonstrated that the lon mutant had a defect in cytotoxicity towards epithelial cells, was less virulent in an amoeba model as well as a mouse acute lung infection model, and impacted on in vivo survival in a rat model of chronic infection. Using qRT-PCR it was demonstrated that the lon mutation led to a down-regulation of Type III secretion genes. The Lon protease also influenced motility and biofilm formation in a mucin-rich environment. Thus alterations in several virulence-related processes in vitro in a lon mutant were reflected by defective virulence in vivo.

  5. Diagnosis of the primary infection by pneumocystis in autopsy specimens from two infants using lung impression smears (touch preps

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    Carolina A. Ponce

    2014-07-01

    Full Text Available The primary infection by Pneumocystis of normal, healthy infants is asymptomatic and goes undiagnosed. Microscopy diagnosis of Pneumocystis was sought in lung impression smears (LIS from two ~3-month-old infants dying unexpectedly in the community. Pneumocystis nuclei and cysts were identified using Hema-Gurr with subsequent Gomori–Grocott staining in the same spot documenting that these stains may be complementary. LIS provide for an observer–dependent, inexpensive, and ready-available method for detection of Pneumocystis in infant lungs.

  6. Dysfunctional CFTR alters the bactericidal activity of human macrophages against Pseudomonas aeruginosa.

    Directory of Open Access Journals (Sweden)

    Paola Del Porto

    Full Text Available Chronic inflammation of the lung, as a consequence of persistent bacterial infections by several opportunistic pathogens represents the main cause of mortality and morbidity in cystic fibrosis (CF patients. Mechanisms leading to increased susceptibility to bacterial infections in CF are not completely known, although the involvement of cystic fibrosis transmembrane conductance regulator (CFTR in microbicidal functions of macrophages is emerging. Tissue macrophages differentiate in situ from infiltrating monocytes, additionally, mature macrophages from different tissues, although having a number of common activities, exhibit variation in some molecular and cellular functions. In order to highlight possible intrinsic macrophage defects due to CFTR dysfunction, we have focused our attention on in vitro differentiated macrophages from human peripheral blood monocytes. Here we report on the contribution of CFTR in the bactericidal activity against Pseudomonas aeruginosa of monocyte derived human macrophages. At first, by real time PCR, immunofluorescence and patch clamp recordings we demonstrated that CFTR is expressed and is mainly localized to surface plasma membranes of human monocyte derived macrophages (MDM where it acts as a cAMP-dependent chloride channel. Next, we evaluated the bactericidal activity of P. aeruginosa infected macrophages from healthy donors and CF patients by antibiotic protection assays. Our results demonstrate that control and CF macrophages do not differ in the phagocytic activity when infected with P. aeruginosa. Rather, although a reduction of intracellular live bacteria was detected in both non-CF and CF cells, the percentage of surviving bacteria was significantly higher in CF cells. These findings further support the role of CFTR in the fundamental functions of innate immune cells including eradication of bacterial infections by macrophages.

  7. Etiology and prevention countermeasures for nosocomial infections in patients with lung cancer treated by chemotherapy%肺癌化疗患者医院感染病原学特点及预防

    Institute of Scientific and Technical Information of China (English)

    徐爱红; 韩琴; 吴丽花

    2014-01-01

    OBJECTIVE To analyze etiology and prevention countermeasures for nosocomial infections in patients with lung cancer treated by chemotherapy ,in order to provide a theoretical basis to reduce infection rate ,improve pulmonary function and life quality of patients .METHODS A retrospective analysis of the clinical data of 193 lung cancer patients treated by chemotherapy in Mar .2007 to Mar .2012 was conducted ,the pathogens and drug sensi-tivity tests were performed ,and countermeasures were analyzed ,data were analyzed with SPSS 13 .0 .RESULTS In 193 patients ,there were 91 cases of nosocomial infections ,the infection rate was 47 .2% .The sputum culture for 91 cases of infections detected 97 strains of bacteria ,including 72 strains of gram negative bacteria ,accounting for 74 .2% ,predominately Pseudomonas aeruginosa and K lebsiella pneumoniae ,accounting for 29 .9% and 17 .5% ;and 22 gram positive strains ,accounting for 22 .7% ;3 strains of fungi ,accounting for 3 .1% .CONCLUSION The risk of nosocomial infections in patients with lung cancer is high ,the pathogenic bacteria are mainly Pseudomonas aeruginosa and K lebsiella pneumoniae ,which have shown high resistance to commonly used antimicrobial drugs . Clinicians should well implement the nutritional support ,psychological nursing ,and specifications of antibacterial medication and invasive operation ,so as to prevent infections and improve the life quality of patients .%目的:分析肺癌化疗患者医院感染病原学特点及预防对策,为降低患者感染率、改善其肺功能及生活质量提供理论依据。方法回顾性分析2007年3月-2012年3月收治的193例行化疗治疗肺癌患者临床资料,进行病原菌、药敏检测,并分析预防对策,数据采用SPSS13.0进行分析。结果193例患者发生医院感染91例,感染率47.2%;91例感染患者痰培养共分离出病原菌97株,其中革兰阴性菌72株占74.2%,以铜绿假单细胞菌和肺炎

  8. High-resolution computed tomographic findings of Aspergillus infection in lung transplant patients

    Energy Technology Data Exchange (ETDEWEB)

    Gazzoni, Fernando Ferreira, E-mail: gazzoni4@gmail.com [Hospital de Clínicas de Porto Alegre, Av. Cristovão Colombo 4105, ap.603-C, Post Code: 90560-005, Porto Alegre, RS (Brazil); Hochhegger, Bruno, E-mail: brunohochhegger@gmail.com [Santa Casa de Porto Alegre, Rua 24 de outubro 925/903, Post Code: 90510-002, Porto Alegre, RS (Brazil); Severo, Luiz Carlos, E-mail: severo@santacasa.tche.br [Federal University of Rio Grande do Sul, Rua Ramiro Barcelos, 2400, 2° andar, Post Code: 90035-003, Porto Alegre, RS (Brazil); Marchiori, Edson, E-mail: edmarchiori@gmail.com [Federal University of Rio de Janeiro, Radiology Department, Av. Pedro Calmon, n° 550 – Cidade Universitária, Post Code: 21941-901, Rio de Janeiro, RJ (Brazil); Pasqualotto, Alessandro, E-mail: acpasqualotto@hotmail.com [Santa Casa de Porto Alegre, Rua 24 de outubro 925/903, Post Code: 90510-002, Porto Alegre, RS (Brazil); Sartori, Ana Paula Garcia, E-mail: ana_sartori@hotmail.com [Santa Casa de Porto Alegre, Rua 24 de outubro 925/903, Post Code: 90510-002, Porto Alegre, RS (Brazil); Schio, Sadi, E-mail: smschio@hotmail.com [Santa Casa de Porto Alegre, Rua 24 de outubro 925/903, Post Code: 90510-002, Porto Alegre, RS (Brazil); Camargo, José, E-mail: jjcamargo@terra.com.br [Santa Casa de Porto Alegre, Rua 24 de outubro 925/903, Post Code: 90510-002, Porto Alegre, RS (Brazil)

    2014-01-15

    Objective: The aim of this study was to assess high-resolution computed tomographic (HRCT) findings at presentation in lung transplant patients diagnosed with pulmonary Aspergillus infection. Materials and methods: We retrospectively reviewed HRCT findings from 23 patients diagnosed with pulmonary aspergillosis. Imaging studies were performed 2–5 days after the onset of symptoms. The patient sample comprised 12 men and 11 women aged 22–59 years (mean age, 43.6 years). All patients had dyspnea, tachypnea, and cough. Diagnoses were established with Platelia Aspergillus enzyme immunoassays for galactomannan antigen detection in bronchoalveolar lavage and recovery of symptoms, and HRCT findings after voriconazole treatment. The HRCT scans were reviewed independently by two observers who reached a consensus decision. Results: The main HRCT pattern, found in 65% (n = 15) of patients, was centrilobular tree-in-bud nodules associated with bronchial thickening. This pattern was described in association with areas of consolidation and ground-glass opacities in 13% (n = 3) of patients. Consolidation and ground-glass opacities were the main pattern in 22% (n = 5) of patients. The pattern of large nodules with and without the halo sign was observed in 13% (n = 3) of patients, and were associated with consolidation and ground-glass opacities in one case. Conclusion: The predominant HRCT findings in lung transplant patients with pulmonary aspergillosis were bilateral bronchial wall thickening and centrilobular opacities with the tree-in-bud pattern. Ground-glass opacities and/or bilateral areas of consolidation were also common findings. Pulmonary nodules with the halo sign were found in only 13% of patients.

  9. Alginate overproduction affects Pseudomonas aeruginosa biofilm structure and function

    DEFF Research Database (Denmark)

    Hentzer, Morten; Teitzel, G.M.; Balzer, G.J.;

    2001-01-01

    During the course of chronic cystic fibrosis (CF) infections, Pseudomonas aeruginosa undergoes a conversion to a mucoid phenotype, which is characterized by overproduction of the exopolysaccharide alginate. Chronic P. aeruginosa infections involve surface-attached, highly antibiotic-resistant com......During the course of chronic cystic fibrosis (CF) infections, Pseudomonas aeruginosa undergoes a conversion to a mucoid phenotype, which is characterized by overproduction of the exopolysaccharide alginate. Chronic P. aeruginosa infections involve surface-attached, highly antibiotic......-resistant communities of microorganisms organized in biofilms. Although biofilm formation and the conversion to mucoidy are both important aspects of CF pathogenesis, the relationship between them is at the present unclear. In this study, we report that the overproduction of alginate affects biofilm development...

  10. Mycobacterium tuberculosis Cell Wall Fragments Released upon Bacterial Contact with the Human Lung Mucosa Alter the Neutrophil Response to Infection

    Science.gov (United States)

    Scordo, Julia M.; Arcos, Jesús; Kelley, Holden V.; Diangelo, Lauren; Sasindran, Smitha J.; Youngmin, Ellie; Wewers, Mark D.; Wang, Shu-Hua; Balada-Llasat, Joan-Miquel; Torrelles, Jordi B.

    2017-01-01

    In 2016, the World Health Organization reported that one person dies of tuberculosis (TB) every 21 s. A host environment that Mycobacterium tuberculosis (M.tb) finds during its route of infection is the lung mucosa bathing the alveolar space located in the deepest regions of the lungs. We published that human lung mucosa, or alveolar lining fluid (ALF), contains an array of hydrolytic enzymes that can significantly alter the M.tb surface during infection by cleaving off parts of its cell wall. This interaction results in two different outcomes: modifications on the M.tb cell wall surface and release of M.tb cell wall fragments into the environment. Typically, one of the first host immune cells at the site of M.tb infection is the neutrophil. Neutrophils can mount an extracellular and intracellular innate immune response to M.tb during infection. We hypothesized that exposure of neutrophils to ALF-induced M.tb released cell wall fragments would prime neutrophils to control M.tb infection better. Our results show that ALF fragments activate neutrophils leading to an increased production of inflammatory cytokines and oxidative radicals. However, neutrophil exposure to these fragments reduces production of chemoattractants (i.e., interleukin-8), and degranulation, with the subsequent reduction of myeloperoxidase release, and does not induce cytotoxicity. Unexpectedly, these ALF fragment-derived modulations in neutrophil activity do not further, either positively or negatively, contribute to the intracellular control of M.tb growth during infection. However, secreted products from neutrophils primed with ALF fragments are capable of regulating the activity of resting macrophages. These results indicate that ALF-induced M.tb fragments could further contribute to the control of M.tb growth and local killing by resident neutrophils by switching on the total oxidative response and limiting migration of neutrophils to the infection site. PMID:28373877

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

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    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.

  12. Streptococcus pneumoniae-induced pneumonia and Citrobacter rodentium-induced gut infection differentially alter vitamin A concentrations in the lung and liver of mice.

    Science.gov (United States)

    Restori, Katherine H; McDaniel, Kaitlin L; Wray, Amanda E; Cantorna, Margherita T; Ross, A Catharine

    2014-03-01

    In the developing world, vitamin A (VA) deficiency is endemic in populations that are also at great risk of morbidity and mortality because of pneumococcal pneumonia and enteric infections. To better understand how lung and gastrointestinal pathogens affect VA status, we assessed VA concentrations in serum, lung, and liver during an invasive pneumonia infection induced by Streptococcus pneumoniae serotype 3, and a noninvasive gut infection induced by Citrobacter rodentium, in vitamin A-adequate (VAA) and vitamin A-deficient (VAD) mice. For pneumonia infection, mice were immunized with pneumococcal polysaccharide serotype 3 (PPS3), or not (infected-control), 5 d prior to intranasal inoculation with S. pneumoniae. Two days post-inoculation, immunization was protective against systemic infection regardless of VA status as PPS3 immunization decreased bacteremia compared with infected-control mice (P pneumonia had less effect on VA status than gastrointestinal infection, predominantly owing to reduced hepatic VA storage at the peak of gut infection.

  13. [Lung disease and HIV infection in children at the Charles de Gaulle university pediatric hospital center in Ouagadougou (Burkina Faso)].

    Science.gov (United States)

    Kouéta, Fla; Yé, Diarra; Dao, Lassina; Zoungrana-Kaboré, Alice; Ouédraogo, Sylvie Armelle P; Napon, M; Sawadogo, Alphonse

    2008-01-01

    To compare the clinical and radiological aspects of lung diseases in HIV-positive and HIV-negative children, we conducted a retrospective case control study covering a 3-year period from January 2003 through December 2005 at Charles de Gaulle University Pediatric Hospital Center in Ouagadougou. HIV-positive patients hospitalised for lung disease were matched to HIV-negative patients controls, hospitalised for the same symptoms, by age and date of hospitalisation. The study included 186 patients (93 HIV-positive and 93 HIV-negative) and collected data on age, sex, clinical signs, radiological signs and short-term course. Of the 93 HIV-positive children suspected to have been contaminated by mother-to-child transmission, 92 had HIV1 and 1 had a double infection of HIV1 and 2. The mean age in both groups was 48 months. Clinically severe lung disease (44%) was more common in HIV-positive children. Radiology showed that interstitial syndrome was significantly more common in HIV-positive children (p=0001) with a sensitivity of 71% and a specificity of 60%. The case-fatality rate was 4.2% among HIV-positive children. This study allows us to remind paediatricians of the importance of lung disease in HIV-infected children. Moreover, the vertical transmission responsible for disease in all our patients shows the need to accelerate the scaling up of the program for prevention of mother-to-child HIV transmission in our country.

  14. Optimizing intravenous fosfomycin dosing in combination with carbapenems for treatment of Pseudomonas aeruginosa infections in critically ill patients based on pharmacokinetic/pharmacodynamic (PK/PD) simulation

    OpenAIRE

    O. Asuphon; P. Montakantikul; J. Houngsaitong; Kiratisin, P.; P. Sonthisombat

    2016-01-01

    Objective: The purpose of the study was to determine the optimal dosing regimen of intravenous fosfomycin for the treatment of Pseudomonas aeruginosa (PA) based on PK/PD targets. Method: A total of 120 PA isolates were recovered from various clinical specimens at university hospital in Thailand. Minimum Inhibitory Concentrations (MICs) of all the isolates were determined by the E-test method. PK parameters were obtained from a published study. Monte Carlo simulation was performed to calcul...

  15. Proteomic profiling of Pseudomonas aeruginosa AES-1R, PAO1 and PA14 reveals potential virulence determinants associated with a transmissible cystic fibrosis-associated strain

    Directory of Open Access Journals (Sweden)

    Hare Nathan J

    2012-01-01

    Full Text Available Abstract Background Pseudomonas aeruginosa is an opportunistic pathogen that is the major cause of morbidity and mortality in patients with cystic fibrosis (CF. While most CF patients are thought to acquire P. aeruginosa from the environment, person-person transmissible strains have been identified in CF clinics worldwide. The molecular basis for transmissibility and colonization of the CF lung remains poorly understood. Results A dual proteomics approach consisting of gel-based and gel-free comparisons were undertaken to analyse protein profiles in a transmissible, early (acute isolate of the Australian epidemic strain 1 (AES-1R, the virulent burns/wound isolate PA14, and the poorly virulent, laboratory-associated strain PAO1. Over 1700 P. aeruginosa proteins were confidently identified. AES-1R protein profiles revealed elevated abundance of proteins associated with virulence and siderophore biosynthesis and acquisition, antibiotic resistance and lipopolysaccharide and fatty acid biosynthesis. The most abundant protein in AES-1R was confirmed as a previously hypothetical protein with sequence similarity to carbohydrate-binding proteins and database search revealed this gene is only found in the CF-associated strain PA2192. The link with CF infection may suggest that transmissible strains have acquired an ability to rapidly interact with host mucosal glycoproteins. Conclusions Our data suggest that AES-1R expresses higher levels of proteins, such as those involved in antibiotic resistance, iron acquisition and virulence that may provide a competitive advantage during early infection in the CF lung. Identification of novel proteins associated with transmissibility and acute infection may aid in deciphering new strategies for intervention to limit P. aeruginosa infections in CF patients.

  16. True microbiota involved in chronic lung infection of cystic fibrosis patients found by culturing and 16S rRNA gene analysis

    DEFF Research Database (Denmark)

    Rudkjøbing, Vibeke Børsholt; Thomsen, Trine R; Alhede, Morten

    2011-01-01

    Patients suffering from cystic fibrosis (CF) develop chronic lung infection. In this study, we investigated the microorganisms present in transplanted CF lungs (n = 5) by standard culturing and 16S rRNA gene analysis. A correspondence between culturing and the molecular methods was observed. In c...

  17. Drastic Attenuation of Pseudomonas aeruginosa Pathogenicity in a Holoxenic Mouse Experimental Model Induced by Subinhibitory Concentrations of Phenyllactic acid (PLA

    Directory of Open Access Journals (Sweden)

    Elena Sasarman

    2007-07-01

    Full Text Available The discovery of communication systems regulating bacterial virulence hasafforded a novel opportunity to control infectious bacteria without interfering withgrowth. In this paper we describe the effect of subinhibitory concentrations of phenyl-lactic acid (PLA on the pathogenicity of Pseudomonas aeruginosa in mice. The animalswere inoculated by oral (p.o., intranasal (i.n., intravenous (i.v. and intraperitoneal (i.p.routes with P. aeruginoasa wild and PLA-treated cultures. The mice were followed upduring 16 days after infection and the body weight, mortality and morbidity rate weremeasured every day. The microbial charge was studied by viable cell counts in lungs,spleen, intestinal mucosa and blood. The mice batches infected with wild P. aeruginosabacterial cultures exhibited high mortality rates (100 % after i.v. and i.p. route and veryhigh cell counts in blood, lungs, intestine and spleen. In contrast, the animal batchesinfected with PLA treated bacterial cultures exhibited good survival rates (0 % mortality and the viable cell counts in the internal organs revealed with one exception the complete abolition of the invasive capacity of the tested strains. In this study, using a mouse infection model we show that D-3-phenyllactic acid (PLA can act as a potent antagonist of Pseudomonas (P. aeruginosa pathogenicity, without interfering with the bacterial growth, as demonstrated by the improvement of the survival rates as well as the clearance of bacterial strains from the body.

  18. Responses of Pseudomonas aeruginosa to antimicrobials

    Directory of Open Access Journals (Sweden)

    Yuji eMorita

    2014-01-01

    Full Text Available Infections caused by Pseudomonas aeruginosa often are hard to treat; inappropriate chemotherapy readily selects multidrug-resistant P. aeruginosa. This organism can be exposed to a wide range of concentrations of antimicrobials during treatment; learning more about the responses of P. aeruginosa to antimicrobials is therefore important. We review here responses of the bacterium P. aeruginosa upon exposure to antimicrobials at levels below the inhibitory concentration.Carbapenems (e.g., imipenem have been shown to induce the formation of thicker and more robust biofilms, while fluoroquinolones (e.g., ciprofloxacin and aminoglycosides (e.g., tobramycin have been shown to induce biofilm formation. Ciprofloxacin also has been demonstrated to enhance the frequency of mutation to carbapenem resistance. Conversely, although macrolides (e.g., azithromycin typically are not effective against P. aeruginosa because of the pseudomonal outer-membrane impermeability and efflux, macrolides do lead to a reduction in virulence factor production. Similarly, tetracycline is not very effective against this organism, but is known to induce the type-III secretion system and consequently enhance cytotoxicity of P. aeruginosa in vivo. Of special note are the effects of antibacterials and disinfectants on pseudomonal efflux systems. Sub-inhibitory concentrations of protein synthesis inhibitors (aminoglycosides, tetracycline, chloramphenicol, etc. induce the MexXY multidrug efflux system. This response is known to be mediated by interference with the translation of the leader peptide PA5471.1, with consequent effects on expression of the PA5471 gene product. Additionally, induction of the MexCD-OprJ multidrug efflux system is observed upon exposure to sub-inhibitory concentrations of disinfectants such as chlorhexidine and benzalkonium. This response is known to be dependent upon the AlgU stress response factor.Altogether, these biological responses of P. aeruginosa

  19. Sequencing and Characterization of Pseudomonas aeruginosa phage JG004

    Directory of Open Access Journals (Sweden)

    Bunk Boyke

    2011-05-01

    Full Text Available Abstract Background Phages could be an important alternative to antibiotics, especially for treatment of multiresistant bacteria as e.g. Pseudomonas aeruginosa. For an effective use of bacteriophages as antimicrobial agents, it is important to understand phage biology but also genes of the bacterial host essential for phage infection. Results We isolated and characterized a lytic Pseudomonas aeruginosa phage, named JG004, and sequenced its genome. Phage JG004 is a lipopolysaccharide specific broad-host-range phage of the Myoviridae phage family. The genome of phage JG004 encodes twelve tRNAs and is highly related to the PAK-P1 phage genome. To investigate phage biology and phage-host interactions, we used transposon mutagenesis of the P. aeruginosa host and identified P. aeruginosa genes, which are essential for phage infection. Analysis of the respective P. aeruginosa mutants revealed several characteristics, such as host receptor and possible spermidine-dependance of phage JG004. Conclusions Whole genome sequencing of phage JG004 in combination with identification of P. aeruginosa host genes essential for infection, allowed insights into JG004 biology, revealed possible resistance mechanisms of the host bacterium such as mutations in LPS and spermidine biosynthesis and can also be used to characterize unknown gene products in P. aeruginosa.

  20. Glycopeptide dendrimers as Pseudomonas aeruginosa biofilm inhibitors.

    Science.gov (United States)

    Reymond, Jean-Louis; Bergmann, Myriam; Darbre, Tamis

    2013-06-01

    Synthetic glycopeptide dendrimers composed of a branched oligopeptide tree structure appended with glycosidic groups at its multiple N-termini were investigated for binding to the Pseudomonas aeruginosa lectins LecB and LecA. These lectins are partly responsible for the formation of antibiotic resistant biofilms in the human pathogenic bacterium P. aeruginosa, which causes lethal airway infections in immune-compromised and cystic fibrosis patients. Glycopeptide dendrimers with high affinity to the lectins were identified by screening of combinatorial libraries. Several of these dendrimers, in particular the LecB specific glycopeptide dendrimers FD2 and D-FD2 and the LecA specific glycopeptide dendrimers GalAG2 and GalBG2, also efficiently block P. aeruginosa biofilm formation and induce biofilm dispersal in vitro. Structure-activity relationship and structural studies are reviewed, in particular the observation that multivalency is essential to the anti-biofilm effect in these dendrimers.

  1. Nuclear Magnetic Resonance Characterization of the Type III Secretion System Tip Chaperone Protein PcrG of Pseudomonas aeruginosa.

    Science.gov (United States)

    Chaudhury, Sukanya; Nordhues, Bryce A; Kaur, Kawaljit; Zhang, Na; De Guzman, Roberto N

    2015-11-01

    Lung infection with Pseudomonas aeruginosa is the leading cause of death among cystic fibrosis patients. To initiate infection, P. aeruginosa assembles a protein nanomachine, the type III secretion system (T3SS), to inject bacterial proteins directly into target host cells. An important regulator of the P. aeruginosa T3SS is the chaperone protein PcrG, which forms a complex with the tip protein, PcrV. In addition to its role as a chaperone to the tip protein, PcrG also regulates protein secretion. PcrG homologues are also important in the T3SS of other pathogens such as Yersinia pestis, the causative agent of bubonic plague. The atomic structure of PcrG or any member of the family of tip protein chaperones is currently unknown. Here, we show by circular dichroism and nuclear magnetic resonance (NMR) spectroscopy that PcrG lacks a tertiary structure. However, it is not completely disordered but contains secondary structures dominated by two long α-helices from residue 16 to 41 and from residue 55 to 76. The helices of PcrG are partially formed, have similar backbone dynamics, and are flexible. NMR titrations show that the entire length of PcrG residues from position 9 to 76 is involved in binding to PcrV. PcrG adds to the growing list of partially folded or unstructured proteins with important roles in type III secretion.

  2. 10 years of prophylaxis with nebulized liposomal amphotericin B and the changing epidemiology of Aspergillus spp. infection in lung transplantation.

    Science.gov (United States)

    Peghin, Maddalena; Monforte, Victor; Martin-Gomez, Maria-Teresa; Ruiz-Camps, Isabel; Berastegui, Cristina; Saez, Berta; Riera, Jordi; Ussetti, Piedad; Solé, Juan; Gavaldá, Joan; Roman, Antonio

    2016-01-01

    The aim of this study was to assess the outcome and tolerability of prophylactic nebulized liposomal amphotericin B (n-LAB) in lung transplant recipients (LTR) and the changing epidemiology of Aspergillus spp. infection and colonization. We performed an observational study including consecutive LTR recipients (2003-2013) undergoing n-LAB prophylaxis lifetime. A total of 412 patients were included (mean postoperative follow-up 2.56 years; IQR 1.01-4.65). Fifty-three (12.8%) patients developed 59 Aspergillus spp. infections, and 22 invasive aspergillosis (overall incidence 5.3%). Since 2009, person-time incidence rates of Aspergillus spp. colonization and infection decreased (2003-2008, 0.19; 2009-2014, 0.09; P = 0.0007), but species with reduced susceptibility or resistance to amphotericin significantly increased (2003-2008, 38.1% vs 2009-2014, 58.1%; P = 0.039). Chronic lung allograft dysfunction (CLAD) was associated with Aspergillus spp. coloni