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Sample records for corynebacterium diphtheriae invasion-associated

  1. Corynebacterium diphtheriae invasion-associated protein (DIP1281 is involved in cell surface organization, adhesion and internalization in epithelial cells

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    Rheinlaender Johannes

    2010-01-01

    Full Text Available Abstract Background Corynebacterium diphtheriae, the causative agent of diphtheria, is well-investigated in respect to toxin production, while little is known about C. diphtheriae factors crucial for colonization of the host. In this study, we investigated the function of surface-associated protein DIP1281, previously annotated as hypothetical invasion-associated protein. Results Microscopic inspection of DIP1281 mutant strains revealed an increased size of the single cells in combination with an altered less club-like shape and formation of chains of cells rather than the typical V-like division forms or palisades of growing C. diphtheriae cells. Cell viability was not impaired. Immuno-fluorescence microscopy, SDS-PAGE and 2-D PAGE of surface proteins revealed clear differences of wild-type and mutant protein patterns, which were verified by atomic force microscopy. DIP1281 mutant cells were not only altered in shape and surface structure but completely lack the ability to adhere to host cells and consequently invade these. Conclusions Our data indicate that DIP1281 is predominantly involved in the organization of the outer surface protein layer rather than in the separation of the peptidoglycan cell wall of dividing bacteria. The adhesion- and invasion-negative phenotype of corresponding mutant strains is an effect of rearrangements of the outer surface.

  2. Corynebacterium ulcerans cutaneous diphtheria.

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    Moore, Luke S P; Leslie, Asuka; Meltzer, Margie; Sandison, Ann; Efstratiou, Androulla; Sriskandan, Shiranee

    2015-09-01

    We describe the case of a patient with cutaneous diphtheria caused by toxigenic Corynebacterium ulcerans who developed a right hand flexor sheath infection and symptoms of sepsis such as fever, tachycardia, and elevated C-reactive protein, after contact with domestic cats and dogs, and a fox. We summarise the epidemiology, clinical presentation, microbiology, diagnosis, therapy, and public health aspects of this disease, with emphasis on improving recognition. In many European countries, C ulcerans has become the organism commonly associated with cutaneous diphtheria, usually seen as an imported tropical disease or resulting from contact with domestic and agricultural animals. Diagnosis relies on bacterial culture and confirmation of toxin production, with management requiring appropriate antimicrobial therapy and prompt administration of antitoxin, if necessary. Early diagnosis is essential for implementation of control measures and clear guidelines are needed to assist clinicians in managing clinical diphtheria. This case was a catalyst to the redrafting of the 2014 national UK interim guidelines for the public health management of diphtheria, released as final guidelines in March, 2015. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Exacerbation of tracheobronchitis due to nontoxigenic Corynebacterium diphtheriae

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    Shinagawa, Shunji; Fujimura, Masaki; Mizuhashi, Keiichi; Takahashi, Shigeo; Noda, Yatsugi; Hirose, Takae; Matsuda, Tamotsu

    1996-01-01

    This is the first case report of exacerbation of tracheobronchitis due to nontoxigenic Corynebacterium diphtheriae in which tracheal pseudomembrane was identified and oral erythromycine therapy was very successful.

  4. Antimicrobial resistance among Brazilian Corynebacterium diphtheriae strains

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    Gabriela Andrade Pereira

    2008-08-01

    Full Text Available The increasing problems with multidrug resistance in relation to Corynebacterium, including C. diphtheriae, are examples of challenges confronting many countries. For this reason, Brazilian C. diphtheriae strains were evaluated by the E-Test for their susceptibility to nine antibacterial drugs used in therapy. Resistance (MIC < 0.002; 0.38 µg/ml to penicillin G was found in 14.8% of the strains tested. Although erythromycin (MIC90 0.75 µg/ml and azithromycin (MIC90 0.064 µg/ml were active against C. diphtheriae in this study, 4.2% of the strains showed decreased susceptibility (MIC 1.0 µg/ml to erythromycin. Multiple resistance profiles were determined by the disk diffusion method using 31 antibiotics. Most C. diphtheriae strains (95.74% showed resistance to mupirocin, aztreonam, ceftazidime, and/or oxacillin, ampicillin, penicillin, tetracycline, clindamycin, lincomycin, and erythromycin. This study presents the antimicrobial susceptibility profiles of Brazilian C. diphtheriae isolates. The data are of value to practitioners, and suggest that some concern exists regarding the use of penicillin.

  5. Toxigenic Corynebacterium ulcerans in human and non-toxigenic Corynebacterium diphtheriae in cat.

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    Detemmerman, L; Rousseaux, D; Efstratiou, A; Schirvel, C; Emmerechts, K; Wybo, I; Soetens, O; Piérard, D

    2013-10-01

    Corynebacterium diphtheriae and Corynebacterium ulcerans are rarely isolated from clinical samples in Belgium. A case of toxigenic C. ulcerans in a woman is described, which confirms that this pathogen is still present. During investigation of the patient's cats, only a non-toxigenic toxin-bearing C. diphtheriae strain was detected.

  6. Draft Genome Sequence of Corynebacterium diphtheriae Biovar Intermedius NCTC 5011

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    Sangal, Vartul; Nicholas P Tucker; Burkovski, Andreas; Hoskisson, Paul A.

    2012-01-01

    We report an annotated draft genome of the human pathogen Corynebacterium diphtheriae bv. intermedius NCTC 5011. This strain is the first C. diphtheriae bv. intermedius strain to be sequenced, and our results provide a useful comparison to the other primary disease-causing biovars, C. diphtheriae bv. gravis and C. diphtheriae bv. mitis. The sequence has been deposited at DDBJ/EMBL/GenBank with the accession number AJVH01000000.

  7. Draft genome sequence of Corynebacterium diphtheriae biovar intermedius NCTC 5011.

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    Sangal, Vartul; Tucker, Nicholas P; Burkovski, Andreas; Hoskisson, Paul A

    2012-09-01

    We report an annotated draft genome of the human pathogen Corynebacterium diphtheriae bv. intermedius NCTC 5011. This strain is the first C. diphtheriae bv. intermedius strain to be sequenced, and our results provide a useful comparison to the other primary disease-causing biovars, C. diphtheriae bv. gravis and C. diphtheriae bv. mitis. The sequence has been deposited at DDBJ/EMBL/GenBank with the accession number AJVH01000000.

  8. Diphtheria due to non-toxigenic corynebacterium diphtheriae: A report of two cases

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    Kanungo R

    2002-01-01

    Full Text Available Diseases due to non-toxigenic strains of Corynebacterium diphtheriae are being increasingly reported. These diseases have been found to occur in vaccinated individuals. We report two cases of diphtheria with myocarditis and polyneuritis caused by non-toxigenic strains of C. diphtheriae. The virulence factors of this organism and the pitfalls in diagnosis have also been discussed.

  9. Human Clinical Isolates of Corynebacterium diphtheriae and Corynebacterium ulcerans Collected in Canada from 1999 to 2003 but Not Fitting Reporting Criteria for Cases of Diphtheria

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    DeWinter, Leanne M.; Bernard, Kathryn A.; Marc G Romney

    2005-01-01

    A 5-year collection of Corynebacterium diphtheriae and Corynebacterium ulcerans human clinical isolates yielded nine isolates from blood cultures of patients with invasive infections, stressing the importance of C. diphtheriae as a serious blood-borne pathogen. Seven percent of C. diphtheriae and 100% of C. ulcerans isolates produced diphtheria toxin, demonstrating that toxigenic corynebacteria continue to circulate.

  10. Human clinical isolates of Corynebacterium diphtheriae and Corynebacterium ulcerans collected in Canada from 1999 to 2003 but not fitting reporting criteria for cases of diphtheria.

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    Dewinter, Leanne M; Bernard, Kathryn A; Romney, Marc G

    2005-07-01

    A 5-year collection of Corynebacterium diphtheriae and Corynebacterium ulcerans human clinical isolates yielded nine isolates from blood cultures of patients with invasive infections, stressing the importance of C. diphtheriae as a serious blood-borne pathogen. Seven percent of C. diphtheriae and 100% of C. ulcerans isolates produced diphtheria toxin, demonstrating that toxigenic corynebacteria continue to circulate.

  11. Diphtheria

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    ... is an acute infection caused by the bacteria Corynebacterium diphtheriae . ... MacGregor RR. Corynebacterium diphtheriae. In: Bennett JE, Dolin R, Blaser MJ, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases . ...

  12. Persistence of Corynebacterium diphtheriae in Delhi & National Capital Region (NCR)

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    Bhagat, S.; Grover, S.S.; Gupta, N.; Roy, R.D.; Khare, S.

    2015-01-01

    Despite the introduction of mass immunization, diphtheria continues to play a major role as a potentially lethal infectious disease in many countries. Delay in the specific therapy of diphtheria may result in death and, therefore, accurate diagnosis of diphtheria is imperative. This study was carried out at National Centre for Disease Control (NCDC), Delhi, India, on samples of suspected diphtheria cases referred from various government hospitals of Delhi and neighbouring areas during 2012-2014. Primary identification of Corynebacterium diphtheriae was done by standard culture, staining and biochemical tests followed by toxigenicity testing by Elek's test on samples positive for C. diphtheriae. The results showed persistence of toxigenic C. diphtheriae in our community indicating the possibility of inadequate immunization coverage. PMID:26609038

  13. Persistence of Corynebacterium diphtheriae in Delhi & National Capital Region (NCR).

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    Bhagat, S; Grover, S S; Gupta, N; Roy, R D; Khare, S

    2015-10-01

    Despite the introduction of mass immunization, diphtheria continues to play a major role as a potentially lethal infectious disease in many countries. Delay in the specific therapy of diphtheria may result in death and, therefore, accurate diagnosis of diphtheria is imperative. This study was carried out at National Centre for Disease Control (NCDC), Delhi, India, on samples of suspected diphtheria cases referred from various government hospitals of Delhi and neighbouring areas during 2012-2014. Primary identification of Corynebacterium diphtheriae was done by standard culture, staining and biochemical tests followed by toxigenicity testing by Elek's test on samples positive for C. diphtheriae. The results showed persistence of toxigenic C. diphtheriae in our community indicating the possibility of inadequate immunization coverage.

  14. A Case of Necrotizing Epiglottitis Due to Nontoxigenic Corynebacterium diphtheriae.

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    Lake, Jessica A; Ehrhardt, Matthew J; Suchi, Mariko; Chun, Robert H; Willoughby, Rodney E

    2015-07-01

    Diphtheria is a rare cause of infection in highly vaccinated populations and may not be recognized by modern clinicians. Infections by nontoxigenic Corynebacterium diphtheriae are emerging. We report the first case of necrotizing epiglottitis secondary to nontoxigenic C diphtheriae. A fully vaccinated child developed fever, poor oral intake, and sore throat and was found to have necrotizing epiglottitis. Necrotizing epiglottitis predominantly occurs in the immunocompromised host. Laboratory evaluation revealed pancytopenia, and bone marrow biopsy was diagnostic for acute lymphoblastic leukemia. Clinicians should be aware of aggressive infections that identify immunocompromised patients. This case highlights the features of a reemerging pathogen, C diphtheriae.

  15. First Draft Genome Sequences of Malaysian Clinical Isolates of Corynebacterium diphtheriae

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    Ahmad, Norazah; Mohd Khalid, Mohd Khairul Nizam; Abd Wahab, Muhammad Adib; Hashim, Rohaidah; Tang, Soo Nee; Liow, Yii Ling; Hamzah, Hazwani; Dahalan, Nurul Ain; Seradja, Valentinus

    2017-01-01

    ABSTRACT Corynebacterium diphtheriae has caused multiple isolated diphtheria cases in Malaysia over the years. Here, we report the first draft genome sequences of 15 Malaysia C. diphtheriae clinical isolates collected from the years 1981 to 2016. PMID:28254972

  16. Corynebacterium diphtheriae infections currently and in the past.

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    Zasada, Aleksandra Anna

    2015-01-01

    Along with the introduction of common obligatory vaccinations against diphtheria, the disease has been limited in developed countries. However, diphtheria is still endemic in developing countries. Due to a growing popularity of visiting these countries, there is a risk of importation of the disease to Europe. Studies revealed that over 60% of persons aged >40 years in the Polish population do not have a protective level of antibodies against diphtheria. Furthermore, an access to diphtheria antitoxin, which is essential in diphtheria treatment, is now hardly accessible in Europe. On the other hand, in many countries, including Poland, new infections caused by non-toxigenic Corynebacterium diphtheriae have been emerged. Such infections are frequently manifested by bacteraemia and endocarditis with a high fatality rate, amounting even to 41%.

  17. Cutaneous Corynebacterium Diphtheriae: A Traveller’s Disease?

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    A Berih

    1995-01-01

    Full Text Available A Canadian soldier incurred a nonhealing traumatic skin ulcer while on duty in Somalia. The diagnosis of localized cutaneous diphtheria was confirmed by isolation of a toxigenic strain of Corynebacterium diphtheriae from the ulcer. The patient was placed in isolation and treated with erythromycin and penicillin for 10 days without antitoxin. He was released when two consecutive daily cultures were negative. Public health officials evaluated his wife, two children and close contacts for carriage, but no carriers or secondary cases were identified. Cutaneous diphtheria as a diagnostic and management patient problem and potential public health problem are discussed.

  18. Bloodstream infection caused by nontoxigenic Corynebacterium diphtheriae in an immunocompromised host in the United States.

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    Wojewoda, Christina M; Koval, Christine E; Wilson, Deborah A; Chakos, Mary H; Harrington, Susan M

    2012-06-01

    Corynebacterium species are well-known causes of catheter-related bloodstream infections. Toxigenic strains of Corynebacterium diphtheriae cause respiratory diphtheria. We report a bloodstream infection caused by a nontoxigenic strain of C. diphtheriae and discuss the epidemiology, possible sources of the infection, and the implications of rapid species identification of corynebacteria.

  19. Tellurite resistance: a putative pitfall in Corynebacterium diphtheriae diagnosis?

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    dos Santos, Louisy Sanches; Antunes, Camila Azevedo; de Oliveira, Daniel Martins; Sant'Anna, Lincoln de Oliveira; Pereira, José Augusto Adler; Hirata Júnior, Raphael; Burkovski, Andreas; Mattos-Guaraldi, Ana Luíza

    2015-11-01

    Corynebacterium diphtheriae strains continue to circulate worldwide causing diphtheria and invasive diseases, such as endocarditis, osteomyelitis, pneumonia and catheter-related infections. Presumptive C. diphtheriae infections diagnosis in a clinical microbiology laboratory requires a primary isolation consisting of a bacterial culture on blood agar and agar containing tellurite (TeO3(2-)). In this study, nine genome sequenced and four unsequenced strains of C. diphtheriae from different sources, including three samples from a recent outbreak in Brazil, were characterized with respect to their growth properties on tellurite-containing agar. Levels of tellurite-resistance (Te(R)) were evaluated by determining the minimum inhibitory concentrations of potassium tellurite (K2TeO3) and by a viability reduction test in solid culture medium with K2TeO3. Significant differences in Te(R) levels of C. diphtheriae strains were observed independent of origin, biovar or presence of the tox gene. Data indicated that the standard initial screening with TeO3(2-)-selective medium for diphtheria bacilli identification may lead to false-negative results in C. diphtheriae diagnosis laboratories.

  20. Non-diphtheriae Corynebacterium species: an emerging respiratory pathogen.

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    Díez-Aguilar, M; Ruiz-Garbajosa, P; Fernández-Olmos, A; Guisado, P; Del Campo, R; Quereda, C; Cantón, R; Meseguer, M A

    2013-06-01

    The purpose of the study was to describe the microbiological and clinical features of ten cases of lower respiratory tract infection due to Corynebacterium striatum, Corynebacterium propinquum and Corynebacterium pseudodiphtheriticum. Respiratory samples were recovered from hospitalised patients who were diagnosed of pneumonia and exacerbations of chronic respiratory infections. The samples were Gram-stained and seeded on conventional bacterial growing media. Bacteria were identified by matrix-assisted linear desorption/ionisation-time-of-flight mass spectrometry (MALDI-TOF MS). Antibiotic susceptibility was tested by the disk diffusion method. All patients presented an acute respiratory onset, most of them in the context of an underlying disease and/or immunosuppression. In all patients, the microscopical examination of Gram-stained respiratory samples showed numerous polymorphonuclear cells and Gram-positive bacilli, suggestive of the Corynebacterium morphotype. A pure culture growth of Corynebacterium was obtained in the majority (72 %) of samples. The conclusions are that non-diphtheriae Corynebacterium species are an emerging cause of respiratory infection among patients with chronic respiratory disease and/or immunosuppression, and cannot always be considered as mere colonisers. The microorganism's predominance in Gram-stained purulent respiratory samples together with abundant growth in the culture is the key for the microbiological diagnosis.

  1. Comparing Galactan Biosynthesis in Mycobacterium tuberculosis and Corynebacterium diphtheriae.

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    Wesener, Darryl A; Levengood, Matthew R; Kiessling, Laura L

    2017-02-17

    The suborder Corynebacterineae encompasses species like Corynebacterium glutamicum, which has been harnessed for industrial production of amino acids, as well as Corynebacterium diphtheriae and Mycobacterium tuberculosis, which cause devastating human diseases. A distinctive component of the Corynebacterineae cell envelope is the mycolyl-arabinogalactan (mAG) complex. The mAG is composed of lipid mycolic acids, and arabinofuranose (Araf) and galactofuranose (Galf) carbohydrate residues. Elucidating microbe-specific differences in mAG composition could advance biotechnological applications and lead to new antimicrobial targets. To this end, we compare and contrast galactan biosynthesis in C. diphtheriae and M. tuberculosis In each species, the galactan is constructed from uridine 5'-diphosphate-α-d-galactofuranose (UDP-Galf), which is generated by the enzyme UDP-galactopyranose mutase (UGM or Glf). UGM and the galactan are essential in M. tuberculosis, but their importance in Corynebacterium species was not known. We show that small molecule inhibitors of UGM impede C. glutamicum growth, suggesting that the galactan is critical in corynebacteria. Previous cell wall analysis data suggest the galactan polymer is longer in mycobacterial species than corynebacterial species. To explore the source of galactan length variation, a C. diphtheriae ortholog of the M. tuberculosis carbohydrate polymerase responsible for the bulk of galactan polymerization, GlfT2, was produced, and its catalytic activity was evaluated. The C. diphtheriae GlfT2 gave rise to shorter polysaccharides than those obtained with the M. tuberculosis GlfT2. These data suggest that GlfT2 alone can influence galactan length. Our results provide tools, both small molecule and genetic, for probing and perturbing the assembly of the Corynebacterineae cell envelope.

  2. Fibrinogen binds to nontoxigenic and toxigenic Corynebacterium diphtheriae strains

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    Priscila Soares Sabbadini

    2010-08-01

    Full Text Available The production of fibrinous exudates may play an important role in determining the outcome of bacterial infection. Although pseudomembrane formation is a characteristic feature of diphtheria, little is known about the fibrinogen (Fbn-binding properties of Corynebacterium diphtheriae strains and the influence of the gene that codes for diphtheria toxin (tox gene in this process. In this study we demonstrated the ability of C. diphtheriae strains to bind to Fbn and to convert Fbn to fibrin. Bacterial interaction with rabbit plasma was evaluated by both slide and tube tests. Interaction of microorganisms with human Fbn was evaluated by both enzyme linked immunosorbent assay (ELISA and fluorescein isothiocyanate-conjugated (FITC Fbn binding assays. Nontoxigenic and toxigenic strains formed bacterial aggregates in the presence of plasma in the slide tests. The ability to convert Fbn to a loose web of fibrin in the plasma solution in the tube tests appeared to be a common characteristic of the species, including strains that do not carry the tox gene. Fbn binding to C. diphtheriae strains occurred at varying intensities, as demonstrated by the FITC-Fbn and ELISA binding assays. Our data suggest that the capacity to bind to Fbn and to convert Fbn to fibrin may play a role in pseudomembrane formation and act as virulence determinants of both nontoxigenic and toxigenic strains.

  3. Fibrinogen binds to nontoxigenic and toxigenic Corynebacterium diphtheriae strains.

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    Sabbadini, Priscila Soares; Genovez, Marcia Rocha Novais; Silva, Cecília Ferreira da; Adelino, Thelma Lúcia Novaes; Santos, Cintia Silva dos; Pereira, Gabriela Andrade; Nagao, Prescilla Emy; Dias, Alexandre Alves de Souza de Oliveira; Mattos-Guaraldi, Ana Luiza; Hirata Júnior, Raphael

    2010-08-01

    The production of fibrinous exudates may play an important role in determining the outcome of bacterial infection. Although pseudomembrane formation is a characteristic feature of diphtheria, little is known about the fibrinogen (Fbn)-binding properties of Corynebacterium diphtheriae strains and the influence of the gene that codes for diphtheria toxin (tox gene) in this process. In this study we demonstrated the ability of C. diphtheriae strains to bind to Fbn and to convert Fbn to fibrin. Bacterial interaction with rabbit plasma was evaluated by both slide and tube tests. Interaction of microorganisms with human Fbn was evaluated by both enzyme linked immunosorbent assay (ELISA) and fluorescein isothiocyanate-conjugated (FITC) Fbn binding assays. Nontoxigenic and toxigenic strains formed bacterial aggregates in the presence of plasma in the slide tests. The ability to convert Fbn to a loose web of fibrin in the plasma solution in the tube tests appeared to be a common characteristic of the species, including strains that do not carry the tox gene. Fbn binding to C. diphtheriae strains occurred at varying intensities, as demonstrated by the FITC-Fbn and ELISA binding assays. Our data suggest that the capacity to bind to Fbn and to convert Fbn to fibrin may play a role in pseudomembrane formation and act as virulence determinants of both nontoxigenic and toxigenic strains.

  4. Rapid detection and molecular differentiation of toxigenic Corynebacterium diphtheriae and Corynebacterium ulcerans strains by LightCycler PCR.

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    Sing, Andreas; Berger, Anja; Schneider-Brachert, Wulf; Holzmann, Thomas; Reischl, Udo

    2011-07-01

    The systemic symptoms of diphtheria are caused by the tox-encoded diphtheria toxin (DT) which is produced by toxigenic Corynebacterium spp. Besides the classical agent C. diphtheriae, the zoonotic pathogen C. ulcerans has increasingly been reported as an emerging pathogen for diphtheria. The reliable detection of toxigenic Corynebacterium spp. is of substantial importance for both diphtheria surveillance in the public health sector and the clinical workup of a patient with diphtherialike symptoms. Since the respective tox genes of C. diphtheriae and C. ulcerans differ from each other in both DNA and amino acid sequence, both tox genes should be covered by novel real-time PCR methods. We describe the development and validation of a LightCycler PCR assay which reliably recognizes tox genes from both C. diphtheriae and C. ulcerans and differentiates the respective target genes by fluorescence resonance energy transfer (FRET) hybridization probe melting curve analysis.

  5. Corynebacterium diphtheriae: genome diversity, population structure and genotyping perspectives.

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    Mokrousov, Igor

    2009-01-01

    The epidemic re-emergence of diphtheria in Russia and the Newly Independent States (NIS) of the former Soviet Union in the 1990s demonstrated the continued threat of this thought to be rare disease. The bacteriophage encoded toxin is a main virulence factor of Corynebacterium diphtheriae, however, an analysis of the first complete genome sequence of C. diphtheriae revealed a recent acquisition of other pathogenicity factors including iron-uptake systems, adhesins and fimbrial proteins as indeed this extracellular pathogen has more possibilities for lateral gene transfer than, e.g., its close relative, mainly intracellular Mycobacterium tuberculosis. C. diphtheriae appears to have a phylogeographical structure mainly represented by area-specific variants whose circulation is under strong influence of human host factors, including health control measures, first of all, vaccination, and social economic conditions. This framework core population structure may be challenged by importation of the endemic and eventually toxigenic strains from new areas thus leading to localized or large epidemics caused directly by imported strains or by bacteriophage-lysogenized indigenous strains converted into toxin production. A feature of C. diphtheriae co-existence with humans is its periodicity: following large epidemic in the 1990s, the present period is marked by increasing heterogeneity of the circulating populations whereas re-emergence of new toxigenic variants along with persistent circulation of invasive non-toxigenic strains appear alarming. To identify and rapidly monitor subtle changes in the genome structure at an infraclonal level during and between epidemics, portable and discriminatory typing methods of C. diphtheriae are still needed. In this view, CRISPRs and minisatellites are promising genomic markers for development of high-resolution typing schemes and databasing of C. diphtheriae.

  6. Purification and structural characterization of siderophore (corynebactin) from Corynebacterium diphtheriae.

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    Zajdowicz, Sheryl; Haller, Jon C; Krafft, Amy E; Hunsucker, Steve W; Mant, Colin T; Duncan, Mark W; Hodges, Robert S; Jones, David N M; Holmes, Randall K

    2012-01-01

    During infection, Corynebacterium diphtheriae must compete with host iron-sequestering mechanisms for iron. C. diphtheriae can acquire iron by a siderophore-dependent iron-uptake pathway, by uptake and degradation of heme, or both. Previous studies showed that production of siderophore (corynebactin) by C. diphtheriae is repressed under high-iron growth conditions by the iron-activated diphtheria toxin repressor (DtxR) and that partially purified corynebactin fails to react in chemical assays for catecholate or hydroxamate compounds. In this study, we purified corynebactin from supernatants of low-iron cultures of the siderophore-overproducing, DtxR-negative mutant strain C. diphtheriae C7(β) ΔdtxR by sequential anion-exchange chromatography on AG1-X2 and Source 15Q resins, followed by reverse-phase high-performance liquid chromatography (RP-HPLC) on Zorbax C8 resin. The Chrome Azurol S (CAS) chemical assay for siderophores was used to detect and measure corynebactin during purification, and the biological activity of purified corynebactin was shown by its ability to promote growth and iron uptake in siderophore-deficient mutant strains of C. diphtheriae under iron-limiting conditions. Mass spectrometry and NMR analysis demonstrated that corynebactin has a novel structure, consisting of a central lysine residue linked through its α- and ε- amino groups by amide bonds to the terminal carboxyl groups of two different citrate residues. Corynebactin from C. diphtheriae is structurally related to staphyloferrin A from Staphylococcus aureus and rhizoferrin from Rhizopus microsporus in which d-ornithine or 1,4-diaminobutane, respectively, replaces the central lysine residue that is present in corynebactin.

  7. Purification and structural characterization of siderophore (corynebactin from Corynebacterium diphtheriae.

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    Sheryl Zajdowicz

    Full Text Available During infection, Corynebacterium diphtheriae must compete with host iron-sequestering mechanisms for iron. C. diphtheriae can acquire iron by a siderophore-dependent iron-uptake pathway, by uptake and degradation of heme, or both. Previous studies showed that production of siderophore (corynebactin by C. diphtheriae is repressed under high-iron growth conditions by the iron-activated diphtheria toxin repressor (DtxR and that partially purified corynebactin fails to react in chemical assays for catecholate or hydroxamate compounds. In this study, we purified corynebactin from supernatants of low-iron cultures of the siderophore-overproducing, DtxR-negative mutant strain C. diphtheriae C7(β ΔdtxR by sequential anion-exchange chromatography on AG1-X2 and Source 15Q resins, followed by reverse-phase high-performance liquid chromatography (RP-HPLC on Zorbax C8 resin. The Chrome Azurol S (CAS chemical assay for siderophores was used to detect and measure corynebactin during purification, and the biological activity of purified corynebactin was shown by its ability to promote growth and iron uptake in siderophore-deficient mutant strains of C. diphtheriae under iron-limiting conditions. Mass spectrometry and NMR analysis demonstrated that corynebactin has a novel structure, consisting of a central lysine residue linked through its α- and ε- amino groups by amide bonds to the terminal carboxyl groups of two different citrate residues. Corynebactin from C. diphtheriae is structurally related to staphyloferrin A from Staphylococcus aureus and rhizoferrin from Rhizopus microsporus in which d-ornithine or 1,4-diaminobutane, respectively, replaces the central lysine residue that is present in corynebactin.

  8. Evaluation and characterisation of A and B fragments of Corynebacterium diphtheriae toxin towards recombinant diphtheria vaccine

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    S Abulmagd

    2013-01-01

    Full Text Available Background: Diphtheria is a highly communicable disease caused by toxin-producing strains of Corynebacterium diphtheriae. Objectives: To evaluate the efficacy of A and B subunits of diphtheria toxin (DT-A, DT-B as potential vaccines against C. diphtheriae. A culture of C. diphtheriae (strain PW 8 was grown on Loeffler plates while Lingood medium was used for production of diphtheria toxin (DT. Materials and Methods: DT was purified and digested to obtain pure DT-A and DT-B and detoxified to obtain diphtheria toxin. Four groups of mice were immunised with different antigens (Ag of C. diphtheriae. Results: The antibody (Ab titres were significantly increased with immunised groups subsequent to three injections. On the other hand, Ab titres were estimated after the three immunisations and the levels of different Ab isotypes were comparatively measured. The levels of various isotypes immune responses showed variation between immunised groups where the IgG subclasses were significantly increased mainly with DPT immunised group. The IgM and IgA were significantly increased with DT-A more than others. Additionally, the evaluation of the cellular immune responses demonstrated that spleen cells from DPT and DT-A groups gave highly significant proliferative response with production of high levels of IL-2 and IFN-γ (Th1/Th2. Separation and purification of DT gene were performed using polymerase chain reaction (PCR and sub-cloned in pGEM-T vector, for further studying of recombinant vaccine. Conclusion: Our results showed the possibility to prepare a potent recombinant vaccine containing whole DT gene or DT-A against C. diphtheriae or could be used in treatment of cancer as it give high levels of IL-2 and IFN-γ.

  9. Sequence Analysis of Toxin Gene–Bearing Corynebacterium diphtheriae Strains, Australia

    Science.gov (United States)

    Mazins, Adam; Graham, Rikki M.A.; Fang, Ning-Xia; Smith, Helen V.; Jennison, Amy V.

    2017-01-01

    By conducting a molecular characterization of Corynebacterium diphtheriae strains in Australia, we identified novel sequences, nonfunctional toxin genes, and 5 recent cases of toxigenic cutaneous diphtheria. These findings highlight the importance of extrapharyngeal infections for toxin gene–bearing (functional or not) and non–toxin gene–bearing C. diphtheriae strains. Continued surveillance is recommended. PMID:27983494

  10. Highly toxinogenic but avirulent Park-Williams 8 strain of Corynebacterium diphtheriae does not produce siderophore.

    OpenAIRE

    Russell, L. M.; Holmes, R K

    1985-01-01

    The highly toxinogenic Park-Williams 8 strain of Corynebacterium diphtheriae grows slowly in vitro and is avirulent. C. diphtheriae Park-Williams 8 is defective in iron uptake and does not produce the corynebacterial siderophore corynebactin. Addition of partially purified corynebactin stimulated iron uptake and growth of iron-deprived C. diphtheriae Park-Williams 8 cells.

  11. Sequence Analysis of Toxin Gene-Bearing Corynebacterium diphtheriae Strains, Australia.

    Science.gov (United States)

    Doyle, Christine J; Mazins, Adam; Graham, Rikki M A; Fang, Ning-Xia; Smith, Helen V; Jennison, Amy V

    2017-01-01

    By conducting a molecular characterization of Corynebacterium diphtheriae strains in Australia, we identified novel sequences, nonfunctional toxin genes, and 5 recent cases of toxigenic cutaneous diphtheria. These findings highlight the importance of extrapharyngeal infections for toxin gene-bearing (functional or not) and non-toxin gene-bearing C. diphtheriae strains. Continued surveillance is recommended.

  12. Corynebacterium ulcerans diphtheria: an emerging zoonosis in Brazil and worldwide.

    Science.gov (United States)

    Dias, Alexandre Alves de Souza de Oliveira; Santos, Louisy Sanchez; Sabbadini, Priscila Soares; Santos, Cíntia Silva; Silva Junior, Feliciano Correa; Napoleão, Fátima; Nagao, Prescilla Emy; Villas-Bôas, Maria Helena Simões; Hirata Junior, Raphael; Guaraldi, Ana Luíza Mattos

    2011-12-01

    The article is a literature review on the emergence of human infections caused by Corynebacterium ulcerans in many countries including Brazil. Articles in Medline/PubMed and SciELO databases published between 1926 and 2011 were reviewed, as well as articles and reports of the Brazilian Ministry of Health. It is presented a fast, cost-effective and easy to perform screening test for the presumptive diagnosis of C. ulcerans and C. diphtheriae infections in most Brazilian public and private laboratories. C. ulcerans spread in many countries and recent isolation of this pathogen in Rio de Janeiro, southeastern Brazil, is a warning to clinicians, veterinarians, and microbiologists on the occurrence of zoonotic diphtheria and C. ulcerans dissemination in urban and rural areas of Brazil and/or Latin America.

  13. METODE CEPAT EKSTRAKSI DNA Corynebacterium diphtheriae UNTUK PEMERIKSAAN PCR

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    Sunarno Sunarno

    2014-10-01

    Full Text Available AbstractDiagnosis of diphtheria caused byCorynebacterium diphtheriaeshould be done immediately since delay of therapy may cause 20-fold increase rate of death. One method of rapid diagnostic to identify diphtheria is by using polymerase chain reaction (PCR. The fundamental issue of this method depends on the DNA, either its quality or quantity. The simple DNA extraction method, which is using mechanical/physical principles with a little of chemical reagents (such as boiling method and the use of sodium hydroxide (NAOH, will have some benefits, such as easy to be performed, low cost, fast, and environmentally friendly. This study aimed to evaluate effectivity and efficiency of boiling method with NaOH to extract DNA of C. diphtheriae compared to the use of a commercial diagnostic kit for PCR assay. We used C. diphtheriae toxygenic(NCTC 10648 isolates, which are grown in blood agar plates. We then prepared the suspensions of cell/colony in aquadest with several dilutions. Each dilution was extracted using boiling method, NaOH and controlled with the use of a commercial diagnostic kit (QiAmp DNA Minikit. The results were evaluated quantitatively with spectrophotometer and qualitatively with gel electrophoresis. The results showed that the extracted DNA from boiling method with NaOH has an adequate quality and quantity for PCR assay (up to 9 CFU/uL cell/reaction. Therefore, it can be summarized that boiling method with NaOH is effective and efficient to be applied in PCR assay forC. diphtheriae.Key words: boiling extraction method, NaOH, C.diphtheriae, PCRAbstrakKematian kasus difteri yang disebabkan oleh Corynebacterium diphtheriaedapat meningkat 20 kali lipat karena keterlambatan pengobatan sehingga penegakan diagnosis harus dilakukan sesegera mungkin. Salah satu metode diagnostik yang cukup cepat untuk mendeteksi penyakit difteri adalah pemeriksaan polymerase chain reaction(PCR. Keberhasilan pemeriksaan PCR dipengaruhi oleh kualitas dan kuantitas

  14. METODE CEPAT EKSTRAKSI DNA Corynebacterium diphtheriae UNTUK PEMERIKSAAN PCR

    Directory of Open Access Journals (Sweden)

    Sunarno Sunarno

    2014-10-01

    Full Text Available AbstractDiagnosis of diphtheria caused byCorynebacterium diphtheriaeshould be done immediately since delay of therapy may cause 20-fold increase rate of death. One method of rapid diagnostic to identify diphtheria is by using polymerase chain reaction (PCR. The fundamental issue of this method depends on the DNA, either its quality or quantity. The simple DNA extraction method, which is using mechanical/physical principles with a little of chemical reagents (such as boiling method and the use of sodium hydroxide (NAOH, will have some benefits, such as easy to be performed, low cost, fast, and environmentally friendly. This study aimed to evaluate effectivity and efficiency of boiling method with NaOH to extract DNA of C. diphtheriae compared to the use of a commercial diagnostic kit for PCR assay. We used C. diphtheriae toxygenic(NCTC 10648 isolates, which are grown in blood agar plates. We then prepared the suspensions of cell/colony in aquadest with several dilutions. Each dilution was extracted using boiling method, NaOH and controlled with the use of a commercial diagnostic kit (QiAmp DNA Minikit. The results were evaluated quantitatively with spectrophotometer and qualitatively with gel electrophoresis. The results showed that the extracted DNA from boiling method with NaOH has an adequate quality and quantity for PCR assay (up to 9 CFU/uL cell/reaction. Therefore, it can be summarized that boiling method with NaOH is effective and efficient to be applied in PCR assay forC. diphtheriae.Key words: boiling extraction method, NaOH, C.diphtheriae, PCRAbstrakKematian kasus difteri yang disebabkan oleh Corynebacterium diphtheriaedapat meningkat 20 kali lipat karena keterlambatan pengobatan sehingga penegakan diagnosis harus dilakukan sesegera mungkin. Salah satu metode diagnostik yang cukup cepat untuk mendeteksi penyakit difteri adalah pemeriksaan polymerase chain reaction(PCR. Keberhasilan pemeriksaan PCR dipengaruhi oleh kualitas dan kuantitas

  15. New diphtheria toxin repressor types depicted in a Romanian collection of Corynebacterium diphtheriae isolates.

    Science.gov (United States)

    Dinu, Sorin; Damian, Maria; Badell, Edgar; Dragomirescu, Cristiana Cerasella; Guiso, Nicole

    2014-10-01

    Corynebacterium diphtheriae is the etiological agent of diphtheria, a potential fatal disease caused by a corynephage toxin. The expression of this diphtheria toxin is controlled via an iron-dependent repressor with various functions (DtxR). Some mutations in the dtxR gene are associated with diminished activity or even with total loss of DtxR function. We conducted a molecular study to characterize the dtxR alleles harbored by 34 isolates of C. diphtheriae recovered from Romanian patients between 1961 and 2007. Three of the seven alleles identified in this study have not previously been described. Two new DtxR types were identified, one of which has an unusual polypeptide length. All the new DtxR types were found in toxigenic isolates, suggesting that they effectively regulate the expression of diphtheria toxin. Furthermore, one of the new DtxR identified was also found in a non-toxigenic isolate, making it a potential source of toxigenic isolates after lysogenic conversion. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Plasticity of Corynebacterium diphtheriae pathogenicity islands revealed by PCR.

    Science.gov (United States)

    Soares, S C; Dorella, F A; Pacheco, L G C; Hirata, R; Mattos-Guaraldi, A L; Azevedo, V; Miyoshi, A

    2011-06-28

    Despite the existence of a vaccine against diphtheria, this disease remains endemic and is reemerging in several regions due to many factors, including variations in genes coding for virulence factors. One common feature of virulence factors is their high concentration in pathogenicity islands (PAIs), very unstable regions acquired via horizontal gene transfer, which has lead to the emergence of various bacterial pathogens. The 13 putative PAIs in Corynebacterium diphtheriae NCTC 13129 and the reemergence of this disease point to the great variability in the PAIs of this species, which may reflect on bacterial life style and physiological versatility. We investigated the relationships between the large number of PAIs in C. diphtheriae and the possible implications of their plasticity in virulence. The GenoFrag software was used to design primers to analyze the genome plasticity of two pathogenicity islands of the reference strain (PiCds 3 and 8) in 11 different strains. We found that PiCd 3 was absent in only two strains, showing genes playing putative important roles in virulence and that only one strain harbored PiCd 8, due to its location in a putative "hotspot" for horizontal gene transfer events.

  17. The first case of septicemia due to nontoxigenic Corynebacterium diphtheriae in Poland: case report

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    Podlasin Regina

    2005-05-01

    Full Text Available Abstract Background Toxigenic strains of Corynebacterium diphtheriae are well known agent of diphtheria. Nontoxigenic strains can cause atypical course of the disease. Invasive diseases caused by C. diphtheriae occur very rare. Case presentation We have described the first case of septicemia and endocarditis due to nontoxigenic C. diphtheriae biotype gravis in Poland. The patient has not belonged to any group of risk such infection. Conclusion The case presented in this article shows unusual case of infection connected with nontoxigenic C. diphtheriae that took place in the area where have been no cases of diphtheria and other C. diphtheriae infections for near ten years. It shows the importance of identifying Corynebacterium isolates at the species level especially when the strain has been isolated from normally sterile sites.

  18. Characterization of Corynebacterium diphtheriae isolates from infected skin lesions in the Northern Territory of Australia.

    Science.gov (United States)

    Gordon, Claire L; Fagan, Peter; Hennessy, Jann; Baird, Robert

    2011-11-01

    Corynebacterium diphtheriae is commonly isolated from cutaneous skin lesions in the Northern Territory of Australia. We prospectively assessed 32 recent isolates from infected skin lesions, in addition to reviewing 192 isolates collected over 5 years for toxin status. No isolates carried the toxin gene. Toxigenic C. diphtheriae is now a rare occurrence in the Northern Territory.

  19. First Report on the Draft Genome Sequences of Corynebacterium diphtheriae Isolates from India

    Science.gov (United States)

    Anandan, Shalini; Rajamani Sekar, Suresh Kumar; Gopi, Radha; Devanga Ragupathi, Naveen Kumar; Ramesh, Srilekha; Verghese, Valsan Philip; Korulla, Sophy; Mathai, Sarah; Sangal, Lucky; Joshi, Sudhir

    2016-01-01

    We report here the draft genome sequences of five Corynebacterium diphtheriae isolates of Indian origin. The C. diphtheriae isolates TH1141, TH510, TH1526, TH1337, and TH2031 belong to sequence type ST-50, ST-295, ST-377, ST-405, and ST-405, with an average genome size of 2.5 Mbp. PMID:27881543

  20. Characterization and comparison of invasive Corynebacterium diphtheriae isolates from France and Poland.

    Science.gov (United States)

    Farfour, E; Badell, E; Zasada, A; Hotzel, H; Tomaso, H; Guillot, S; Guiso, N

    2012-01-01

    Corynebacterium diphtheriae, the agent of diphtheria, is rarely responsible for bacteremia. However, high numbers of bacteremia have been reported in countries with extensive immunization coverage. Here, we used molecular and phenotypic tools to characterize and compare 42 invasive isolates collected in France (including New Caledonia) and Poland over a 23-year period.

  1. Structure of a DsbF homologue from Corynebacterium diphtheriae.

    Science.gov (United States)

    Um, Si-Hyeon; Kim, Jin-Sik; Lee, Kangseok; Ha, Nam-Chul

    2014-09-01

    Disulfide-bond formation, mediated by the Dsb family of proteins, is important in the correct folding of secreted or extracellular proteins in bacteria. In Gram-negative bacteria, disulfide bonds are introduced into the folding proteins in the periplasm by DsbA. DsbE from Escherichia coli has been implicated in the reduction of disulfide bonds in the maturation of cytochrome c. The Gram-positive bacterium Mycobacterium tuberculosis encodes DsbE and its homologue DsbF, the structures of which have been determined. However, the two mycobacterial proteins are able to oxidatively fold a protein in vitro, unlike DsbE from E. coli. In this study, the crystal structure of a DsbE or DsbF homologue protein from Corynebacterium diphtheriae has been determined, which revealed a thioredoxin-like domain with a typical CXXC active site. Structural comparison with M. tuberculosis DsbF would help in understanding the function of the C. diphtheriae protein.

  2. Late-onset prosthetic valve endocarditis caused by nontoxigenic Corynebacterium diphtheriae.

    Science.gov (United States)

    El-Hazmi, Malak M

    2015-08-29

    In developed countries, Corynebacterium diphtheriae infection is rare due to efficient immunization programs. However, cases of nontoxigenic strains of C. diphtheriae infections, including endocarditis, have been reported recently. Although the incidence remains low, these infections are associated with high morbidity and mortality. This report describes the first and atypical case of bacteremia and endocarditis caused by nontoxigenic C. diphtheriae var. gravis after introduction of immunization in the Kingdom of Saudi Arabia (KSA).

  3. [THE COMPARATIVE ANALYSIS OF TECHNIQUES OF IDENTIFICATION OF CORYNEBACTERIUM NON DIPHTHERIAE].

    Science.gov (United States)

    Kharseeva, G G; Voronina, N A; Mironov, A Yu; Alutina, E L

    2015-12-01

    The comparative analysis was carried out concerning effectiveness of three techniques of identification of Corynebacterium non diphtheriae: bacteriological, molecular genetic (sequenation on 16SpRNA) andmass-spectrometric (MALDI-ToFMS). The analysis covered 49 strains of Corynebacterium non diphtheriae (C.pseudodiphheriticum, C.amycolatum, C.propinquum, C.falsenii) and 2 strains of Corynebacterium diphtheriae isolated under various pathology form urogenital tract and upper respiratory ways. The corinbacteria were identified using bacteriologic technique, sequenation on 16SpRNA and mass-spectrometric technique (MALDIToF MS). The full concordance of results of species' identification was marked in 26 (51%) of strains of Corynebacterium non diphtheriae at using three analysis techniques; in 43 (84.3%) strains--at comparison of bacteriologic technique with sequenation on 16S pRNA and in 29 (57%)--at mass-spectrometric analysis and sequenation on 16S pRNA. The bacteriologic technique is effective for identification of Corynebacterium diphtheriae. The precise establishment of species belonging of corynebacteria with variable biochemical characteristics the molecular genetic technique of analysis is to be applied. The mass-spectrometric technique (MALDI-ToF MS) requires further renewal of data bases for identifying larger spectrum of representatives of genus Corynebacterium.

  4. Isolamento de Corynebacterium diphtheriae de líquido espermático Isolation of Corynebacterium diphtheriae from sperm

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    Thaís Lisbôa Machado

    1989-06-01

    Full Text Available Descrevemos o isolamento de Corynebacterium diphtheriae toxígeno de espermocultura. O microrganismo foi identificado pelo teste de fluorescência sob luz ultravioleta, pesquisa da enzima pirazina-carboxilamidase (Pyz, testes de virulência in vitro e in vivo (imunodifusão radial simples, cultura de células e teste intradérmico em cobaio. A amostra foi inicialmente considerada atoxígena pelo teste de imunodifusão radial simples, mas sua virulência foi observada posteriormente quando os testes acima foram aplicados. Sem adecuada especificação, a amostra poderia ter sido considerada como um "difteróide".The isolation of tosigenic Corynebacterum diphtheriae from sperm is reported. The organism was identified through the investigation of fluorescence under the UV light, the presence of pirazinecarboxilamidase enzyme (Pyz, in vitro and in vivo and virulence methods (single radial immunodiffusion, cell culture, guiena pig intradermic test. The strain was initially cosnsidered montoxinogenic by single radial immunodiffusion, but its virulence was observed afterwards, when we applied the tests already mentioned. The strain could be considered a "Diphtheroid" without adequate specification.

  5. [Etiologic role of Corynebacterium non diphtheriae in patients with different pathology].

    Science.gov (United States)

    Kraeva, L A; Manina, Zh N; Tseneva, G Ia; Radchenko, A G

    2007-01-01

    Bacteriologic examination of 1589 patients showed that, aside from C. diphtheriae, 11% of acute upper respiratory tract infections were caused by other Corynebacterium species. Such bacteria can cause infections of various localizations (bronchitis, pyelonephritis, urethritis, colpitis, dermatitis, arthritis, etc.). C. pseudodiphtheriticum and C. xerosis were isolated from clinical specimens most frequently. Corynebacterium spp. have adhesive, hemolytic, hemagglutinating, and neuraminidase activity; some of them are highly pathogenic. The most virulent, were following species: C. diphtheriae, C. pseudotuberculosis, C. urealyticum, and C. ulcerans. Corynebacterium non diphtheriae were frequently isolated from clinical specimens in association with staphylococci and streptococci. In such cases, factors of pathogenicity and resistance to antibiotics were more pronounced. Strains isolated with association with other bacteria have lost susceptibility to tetracycline, oleandomycin, penicillin, and erythromycin. It is important to be vigilant about bacteria from Corynebacterium genus in clinical settings, and thoroughly study their biologic characteristics, especially in immunocompromised patients.

  6. Úlceras leishmanióticas cutâneas com presença de Corynebacterium diphtheriae Cutaneous leishmaniotic ulcers with Corynebacterium diphtheriae

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    Luis Angel Vera

    2002-08-01

    Full Text Available Em um estudo prospectivo para avaliar a influência da infecção bacteriana secundária na evolução da leishmaniose cutânea, em Corte de Pedra (Bahia, obteve-se o isolamento de Corynebacterium diphtheriae em 7(8,3% de 84 pacientes portadores de úlceras, avaliados. Devido ao pequeno número de pacientes com a presença da bactéria na úlcera, não foi possível concluir se Corynebacterium diphtheriae comporta-se apenas como colonizante, nem sobre a sua influência no processo de cicatrização da úlcera leishmaniótica.In a prospective study to evaluate the influence of secondary bacterial infection on the evaluation of cutaneous leishmaniasis, in Corte de Pedra (Bahia, we isolated Corynebacterium diphtheriae in 7 (8.3% out of 84 patients with ulcers studied. Due to the small number of patients with the presence of the bacteria in the ulcer, we could not conclude whether Corynebacterium diphtheriae behaves only as a colonizer nor its influence on the healing of the leishmaniotic ulcer.

  7. The draft genome sequence of Corynebacterium diphtheriae bv. mitis NCTC 3529 reveals significant diversity between the primary disease-causing biovars.

    Science.gov (United States)

    Sangal, Vartul; Tucker, Nicholas P; Burkovski, Andreas; Hoskisson, Paul A

    2012-06-01

    We report the draft genome of the human pathogen Corynebacterium diphtheriae bv. mitis NCTC 3529. This is the first C. diphtheriae bv. mitis strain to be sequenced and reveals significant differences from the other primary biovar, C. diphtheriae bv. gravis.

  8. The Draft Genome Sequence of Corynebacterium diphtheriae bv. mitis NCTC 3529 Reveals Significant Diversity between the Primary Disease-Causing Biovars

    OpenAIRE

    Sangal, Vartul; Nicholas P Tucker; Burkovski, Andreas; Hoskisson, Paul A.

    2012-01-01

    We report the draft genome of the human pathogen Corynebacterium diphtheriae bv. mitis NCTC 3529. This is the first C. diphtheriae bv. mitis strain to be sequenced and reveals significant differences from the other primary biovar, C. diphtheriae bv. gravis.

  9. Corynebacterium ulcerans 0102 carries the gene encoding diphtheria toxin on a prophage different from the C. diphtheriae NCTC 13129 prophage

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    Sekizuka Tsuyoshi

    2012-05-01

    Full Text Available Abstract Background Corynebacterium ulcerans can cause a diphtheria-like illness, especially when the bacterium is lysogenized with a tox gene-carrying bacteriophage that produces diphtheria toxin. Acquisition of toxigenicity upon phage lysogenization is a common feature of C. ulcerans and C. diphtheriae. However, because of a lack of C. ulcerans genome information, a detailed comparison of prophages has not been possible between these two clinically important and closely related bacterial species. Results We determined the whole genome sequence of the toxigenic C. ulcerans 0102 isolated in Japan. The genomic sequence showed a striking similarity with that of Corynebacterium pseudotuberculosis and, to a lesser extent, with that of C. diphtheriae. The 0102 genome contained three distinct prophages. One of these, ΦCULC0102-I, was a tox-positive prophage containing genes in the same structural order as for tox-positive C. diphtheriae prophages. However, the primary structures of the individual genes involved in the phage machinery showed little homology between the two counterparts. Conclusion Taken together, these results suggest that the tox-positive prophage in this strain of C. ulcerans has a distinct origin from that of C. diphtheriae NCTC 13129.

  10. The individual and common repertoire of DNA-binding transcriptional regulators of Corynebacterium glutamicum, Corynebacterium efficiens, Corynebacterium diphtheriae and Corynebacterium jeikeium deduced from the complete genome sequences

    Directory of Open Access Journals (Sweden)

    Kalinowski Jörn

    2005-06-01

    Full Text Available Abstract Background The genus Corynebacterium includes Gram-positive microorganisms of great biotechnologically importance, such as Corynebacterium glutamicum and Corynebacterium efficiens, as well as serious human pathogens, such as Corynebacterium diphtheriae and Corynebacterium jeikeium. Although genome sequences of the respective species have been determined recently, the knowledge about the repertoire of transcriptional regulators and the architecture of global regulatory networks is scarce. Here, we apply a combination of bioinformatic tools and a comparative genomic approach to identify and characterize a set of conserved DNA-binding transcriptional regulators in the four corynebacterial genomes. Results A collection of 127 DNA-binding transcriptional regulators was identified in the C. glutamicum ATCC 13032 genome, whereas 103 regulators were detected in C. efficiens YS-314, 63 in C. diphtheriae NCTC 13129 and 55 in C. jeikeium K411. According to amino acid sequence similarities and protein structure predictions, the DNA-binding transcriptional regulators were grouped into 25 regulatory protein families. The common set of DNA-binding transcriptional regulators present in the four corynebacterial genomes consists of 28 proteins that are apparently involved in the regulation of cell division and septation, SOS and stress response, carbohydrate metabolism and macroelement and metal homeostasis. Conclusion This work describes characteristic features of a set of conserved DNA-binding transcriptional regulators present within the corynebacterial core genome. The knowledge on the physiological function of these proteins should not only contribute to our understanding of the regulation of gene expression but will also provide the basis for comprehensive modeling of transcriptional regulatory networks of these species.

  11. Corynebacterium diphtheriae in a free-roaming red fox: case report and historical review on diphtheria in animals.

    Science.gov (United States)

    Sing, Andreas; Konrad, Regina; Meinel, Dominik M; Mauder, Norman; Schwabe, Ingo; Sting, Reinhard

    2016-08-01

    Corynebacterium diphtheriae, the classical causative agent of diphtheria, is considered to be nearly restricted to humans. Here we report the first finding of a non-toxigenic C. diphtheriae biovar belfanti strain in a free-roaming wild animal. The strain obtained from the subcutis and mammary gland of a dead red fox (Vulpes vulpes) was characterized by biochemical and molecular methods including MALDI-TOF and Multi Locus Sequence Typing. Since C. diphtheriae infections of animals, usually with close contact to humans, are reported only very rarely, an intense review comprising also scientific literature from the beginning of the 20th century was performed. Besides the present case, only 11 previously reported C. diphtheriae animal infections could be verified using current scientific criteria. Our report is the first on the isolation of C. diphtheriae from a wildlife animal without any previous human contact. In contrast, the very few unambiguous publications on C. diphtheriae in animals referred to livestock or pet animals with close human contact. C. diphtheriae carriage in animals has to be considered as an exceptionally rare event.

  12. POTENSI GEN dtx DAN dtxR SEBAGAI MARKER UNTUK DETEKSI DAN PEMERIKSAAN TOKSIGENISITAS Corynebacterium diphtheriae

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    Sunarno Sunarno

    2013-05-01

    Full Text Available Abstract.   Corynebacterium diphtheriae is the causative agent of diphtheria. The main virulence determinant of the bacteria is diphtheria toxin, the cause of the systemic complication seen with diphtheria. Production of diphtheria toxin by toxigenic strain encoded by dtx/tox gene and repressed by dtxR gene. Gold standard for bacterial toxigenicity test carried out by conventional methods (Elek test, Guinea pig and vero cell cytotoxicity. However, Elek test have variety result, time consume and problem of the reagent availability. On the other hand, the animal (Guinea pig testing was opposed by many animal lovers and the vero cell cytotoxicity test require high cost. The study purposed to evaluate the using of dtx and dtxR genes as a detection marker of C.diphtheriae and bacterial toxigenicity test simultaneusly by Multiplex PCR. The study examined 44 bacterial and fungal isolates, included 22 C.diphtheriae (4 reference strains and 18 clinical isolates, 5 other specieses of Corynebacterium  (reference strains and 17 non-Corynebacterium (10 reference strains and 7 stock cultures . All of sample were examined by Multiplex PCR for 2 primer pairs targeted dtx and dtxR genes. The study showed that the Multiplex PCR for dtx and dtxR as target genes able to detect all of sample correctly thus concluded that dtx and dtxR genes could be used as a marker for alternative detection and toxigenicity test of C.diphtheriae by Multiplex PCR rapidly and accuratelly. Key words: Corynebacterium diphtheriae, dtx, dan dtxR Abstrak. Corynebacterium diphtheriae merupakan agen penyebab penyakit difteri.. Faktor virulensi utama  C. diphtheriae adalah toksigenisitas (kemampuan memproduksi toksin bakteri toxin. Produksi toksin diatur seperangkat gen yang disebut gen tox/dtx dan diregulasi oleh gen dtxR. Gold standard untuk pemeriksaan toksigenisitas C.diphtheriae adalah dengan metode konvensional (Elek test, Guinea pig dan vero cell cytotoxigenicity,namun  Elek test

  13. Colonisation with toxigenic Corynebacterium diphtheriae in a Scottish burns patient, June 2015.

    Science.gov (United States)

    Deshpande, Ashutosh; Inkster, Teresa; Hamilton, Kate; Litt, David; Fry, Norman; Kennedy, Iain T R; Shookhye-Dickson, Jacqueline; Hill, Robert L R

    2015-01-01

    On 12 June 2015, Corynebacterium diphtheriae was identified in a skin swab from a burns patient in Scotland. The isolate was confirmed to be genotypically and phenotypically toxigenic. Multilocus sequence typing of three patient isolates yielded sequence type ST 125. The patient was clinically well. We summarise findings of this case, and results of close contact identification and screening: 12 family and close contacts and 32 hospital staff have been found negative for C. diphtheriae.

  14. Prevalence of diphtheria and tetanus antibodies and circulation of Corynebacterium diphtheriae in São Paulo, Brazil

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    K.G. Divino-Goes

    2007-12-01

    Full Text Available The introduction of routine vaccination against tetanus and diphtheria in Brazil has decreased the incidence and changed the epidemiology of both diseases. We then investigated the prevalence of Corynebacterium diphtheriae carrier status and diphtheria and tetanus immunity in São Paulo, Brazil. From November 2001 to March 2003, 374 individuals were tested for the presence of C. diphtheriae in the naso-oropharynx and of serum diphtheria and tetanus antibodies. Participants were all healthy individuals without acute or chronic pathologies and they were stratified by age as follows: 0-12 months and 1-4, 5-9, 10-14, 15-24, 25-39, 40-59, and ³60 years. Antibodies were assessed using a double-antigen ELISA. C. diphtheriae species were identified by biochemical analysis and toxigenicity was assessed by the Elek test. For diphtheria, full protection (antibodies ³0.1 IU/mL was present in 84% of the individuals, 15% had basic protection (antibodies ³0.01 and <0.1 IU/mL and 1% were susceptible (antibodies <0.01 IU/mL. Full tetanus protection (antibodies ³0.1 IU/mL was present in 79% of the participants, 18% had basic protection (antibodies ³0.01 and <0.1 IU/mL and 3% were susceptible (antibodies <0.01 IU/mL. The geometric mean of diphtheria and tetanus antibodies reached the highest values at 5-9 years and decreased until the 40-59-year age range, increasing again in individuals over 60 years. Three participants (0.8% were carriers of C. diphtheriae, all non-toxigenic strains. The present results demonstrate the clear need of periodic booster for tetanus and diphtheria vaccine in adolescents and adults after primary immunization in childhood.

  15. Prevalence of diphtheria and tetanus antibodies and circulation of Corynebacterium diphtheriae in São Paulo, Brazil.

    Science.gov (United States)

    Divino-Goes, K G; Moraes-Pinto, M I de; Dinelli, M I S; Casagrande, S T; Bonetti, T C S; Andrade, P R; Weckx, L Y

    2007-12-01

    The introduction of routine vaccination against tetanus and diphtheria in Brazil has decreased the incidence and changed the epidemiology of both diseases. We then investigated the prevalence of Corynebacterium diphtheriae carrier status and diphtheria and tetanus immunity in São Paulo, Brazil. From November 2001 to March 2003, 374 individuals were tested for the presence of C. diphtheriae in the naso-oropharynx and of serum diphtheria and tetanus antibodies. Participants were all healthy individuals without acute or chronic pathologies and they were stratified by age as follows: 0-12 months and 1-4, 5-9, 10-14, 15-24, 25-39, 40-59, and > or =60 years. Antibodies were assessed using a double-antigen ELISA. C. diphtheriae species were identified by biochemical analysis and toxigenicity was assessed by the Elek test. For diphtheria, full protection (antibodies > or =0.1 IU/mL) was present in 84% of the individuals, 15% had basic protection (antibodies > or =0.01 and antibodies antibodies > or =0.1 IU/mL) was present in 79% of the participants, 18% had basic protection (antibodies > or =0.01 and antibodies diphtheria and tetanus antibodies reached the highest values at 5-9 years and decreased until the 40-59-year age range, increasing again in individuals over 60 years. Three participants (0.8%) were carriers of C. diphtheriae, all non-toxigenic strains. The present results demonstrate the clear need of periodic booster for tetanus and diphtheria vaccine in adolescents and adults after primary immunization in childhood.

  16. Genomic analysis of a nontoxigenic, invasive Corynebacterium diphtheriae strain from Brazil

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    Fernando Encinas

    2015-09-01

    Full Text Available We report the complete genome sequence and analysis of an invasive Corynebacterium diphtheriae strain that caused endocarditis in Rio de Janeiro, Brazil. It was selected for sequencing on the basis of the current relevance of nontoxigenic strains for public health. The genomic information was explored in the context of diversity, plasticity and genetic relatedness with other contemporary strains.

  17. Nontoxigenic highly pathogenic clone of Corynebacterium diphtheriae, Poland, 2004-2012.

    Science.gov (United States)

    Zasada, Aleksandra A

    2013-11-01

    Twenty-five cases of nontoxigenic Corynebacterium diphtheriae infection were recorded in Poland during 2004-2012, of which 18 were invasive. Alcoholism, homelessness, hepatic cirrhosis, and dental caries were predisposing factors for infection. However, for 17% of cases, no concomitant diseases or predisposing factors were found.

  18. Genomic analysis of a nontoxigenic, invasive Corynebacterium diphtheriae strain from Brazil.

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    Encinas, Fernando; Marin, Michel A; Ramos, Juliana N; Vieira, Verônica V; Mattos-Guaraldi, Ana Luiza; Vicente, Ana Carolina P

    2015-09-01

    We report the complete genome sequence and analysis of an invasive Corynebacterium diphtheriae strain that caused endocarditis in Rio de Janeiro, Brazil. It was selected for sequencing on the basis of the current relevance of nontoxigenic strains for public health. The genomic information was explored in the context of diversity, plasticity and genetic relatedness with other contemporary strains.

  19. Process optimization for an industrial-scale production of Diphtheria toxin by Corynebacterium diphtheriae PW8.

    Science.gov (United States)

    Suwanpatcharakul, Maethichai; Pakdeecharoen, Chompunut; Visuttitewin, Supitcha; Pesirikan, Norapath; Chauvatcharin, Somchai; Pongtharangkul, Thunyarat

    2016-11-01

    In this study, several parameters affecting the toxin production of Corynebacterium diphtheriae Parke Williams 8 (PW8) were investigated in detail. The comparison studies of amino acid profile in NZ Amine A-based medium (NZ medium) and beef digest-based medium (BD medium) suggested that an insufficient supply of amino acids was not responsible for low toxin yield observed in NZ medium. Supplementation of additional amino acids and growth promoting nutrient (in a form of yeast extract) into NZ medium enhanced only cell growth but not toxin production. Thus, BD medium was selected as the most suitable base medium for toxin production as it gave a significantly higher limit of flocculation (93 ± 0 Lf/ml) than NZ medium (46 ± 0 Lf/ml). Interestingly, a supplementation of 0.2% YE into BD medium resulted in a significant increase in growth as well as toxin production (235 ± 5 Lf/ml). In conclusion, consistently high toxin titer (174-239 Lf/ml) could be obtained from BD medium at a 5 L-scale production as long as 1) the protein content of BD medium was at least 24 g/L, 2) the iron content was below 0.15 ppm and 3) 0.2% YE was supplemented into the medium.

  20. Diphtheria in the Republic of Georgia: Use of Molecular Typing Techniques for Characterization of Corynebacterium diphtheriae Strains

    Science.gov (United States)

    Sulakvelidze, Alexander; Kekelidze, Merab; Gomelauri, Tsaro; Deng, Yingkang; Khetsuriani, Nino; Kobaidze, Ketino; De Zoysa, Aruni; Efstratiou, Androulla; Morris, J. Glenn; Imnadze, Paata

    1999-01-01

    Sixty-six Corynebacterium diphtheriae strains (62 of the gravis biotype and 4 of the mitis biotype) isolated during the Georgian diphtheria epidemic of 1993 to 1998 and 13 non-Georgian C. diphtheriae strains (10 Russian and 3 reference isolates) were characterized by (i) biotyping, (ii) toxigenicity testing with the Elek assay and PCR, (iii) the randomly amplified polymorphic DNA (RAPD) technique, and (iv) pulsed-field gel electrophoresis (PFGE). Fifteen selected strains were ribotyped. Six RAPD types and 15 PFGE patterns were identified among all strains examined, and 12 ribotypes were found among the 15 strains that were ribotyped. The Georgian epidemic apparently was caused by one major clonal group of C. diphtheriae (PFGE type A, ribotype R1), which was identical to the predominant epidemic strain(s) isolated during the concurrent diphtheria epidemic in Russia. A dendrogram based on the PFGE patterns revealed profound differences between the minor (nonpredominant) epidemic strains found in Georgia and Russia. The methodologies for RAPD typing, ribotyping, and PFGE typing of C. diphtheriae strains were improved to enable rapid and convenient molecular typing of the strains. The RAPD technique was adequate for biotype differentiation; however, PFGE and ribotyping were better (and equal to each other) at discriminating between epidemiologically related and unrelated isolates. PMID:10488190

  1. Identification of Corynebacterium diphtheriae gene involved in adherence to epithelial cells.

    Science.gov (United States)

    Kolodkina, Valentina; Denisevich, Tatyana; Titov, Leonid

    2011-03-01

    Corynebacterium diphtheriae the causative pathogen of human diphtheria infects the nasopharynx or skin. Although diphtheria has been extensively studied, little is known about the two key aspects of C. diphtheriae invasiveness: colonization and invasion. The role of adhesive properties in establishing the infection of C. diphtheriae strains, independent of toxin production, still needs to be clarified. In this study, we describe a novel gene involved in adherence to epithelial cells. Transformation of C. diphtheriae 225, biotype gravis, ribotype St-Petersburg by EZ:TN(KAN-2)Tnp Transposome was undertaken. A C. diphtheriae 225 Tn5 insertion library of 2800 mutants was created. Five hundred and eighty five transformants were qualitatively screened for reduced adherence to HEp-2 cells by an adherence assay. One mutant strain consistently exhibiting 15.2% of the wild-type adherence was isolated. The DNA flanking the transposon was identified by inverse PCR and subsequent sequencing. The disrupted gene was 94% identical to the C. diphtheriae DIP1621 gene that belongs to unclassified genes. In conclusion, the disruption of the C. diphtheriae DIP1621 gene led to decreased adherence to epithelial cells; its exact function remains to be established.

  2. Prediction of DtxR regulon: Identification of binding sites and operons controlled by Diphtheria toxin repressor in Corynebacterium diphtheriae

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    Hasnain Seyed

    2004-09-01

    Full Text Available Abstract Background The diphtheria toxin repressor, DtxR, of Corynebacterium diphtheriae has been shown to be an iron-activated transcription regulator that controls not only the expression of diphtheria toxin but also of iron uptake genes. This study aims to identify putative binding sites and operons controlled by DtxR to understand the role of DtxR in patho-physiology of Corynebacterium diphtheriae. Result Positional Shannon relative entropy method was used to build the DtxR-binding site recognition profile and the later was used to identify putative regulatory sites of DtxR within C. diphtheriae genome. In addition, DtxR-regulated operons were also identified taking into account the predicted DtxR regulatory sites and genome annotation. Few of the predicted motifs were experimentally validated by electrophoretic mobility shift assay. The analysis identifies motifs upstream to the novel iron-regulated genes that code for Formamidopyrimidine-DNA glycosylase (FpG, an enzyme involved in DNA-repair and starvation inducible DNA-binding protein (Dps which is involved in iron storage and oxidative stress defense. In addition, we have found the DtxR motifs upstream to the genes that code for sortase which catalyzes anchoring of host-interacting proteins to the cell wall of pathogenic bacteria and the proteins of secretory system which could be involved in translocation of various iron-regulated virulence factors including diphtheria toxin. Conclusions We have used an in silico approach to identify the putative binding sites and genes controlled by DtxR in Corynebacterium diphtheriae. Our analysis shows that DtxR could provide a molecular link between Fe+2-induced Fenton's reaction and protection of DNA from oxidative damage. DtxR-regulated Dps prevents lethal combination of Fe+2 and H2O2 and also protects DNA by nonspecific DNA-binding. In addition DtxR could play an important role in host interaction and virulence by regulating the levels of sortase

  3. Induction of the NFκ-B signal transduction pathway in response to Corynebacterium diphtheriae infection.

    Science.gov (United States)

    Ott, Lisa; Scholz, Brigitte; Höller, Martina; Hasselt, Kristin; Ensser, Armin; Burkovski, Andreas

    2013-01-01

    Corynebacterium diphtheriae, the causative agent of diphtheria, has been thoroughly studied with respect to toxin production and pili formation, while knowledge on host responses to C. diphtheriae infection is limited. In this study, we studied adhesion to and invasion of epithelial cells by different C. diphtheriae isolates. When NFκ-B reporter cell lines were used to monitor the effect of C. diphtheriae infection on human cells, strain-specific differences were observed. While adhesion to host cells had no effect, a correlation of invasion rate with NFκ-B induction was found, which indicates that internalization of bacteria is crucial for NFκ-B induction. Immunofluorescence microscopy experiments used to support the reporter assays showed that translocation of p65, as a hallmark of NFκ-B induction, was only observed in association with cell invasion by C. diphtheriae. Our data indicate that the response of epithelial cells to C. diphtheriae infection is determined by internalization of bacteria and that invasion of these cells is an active process; tetracycline-treated C. diphtheriae was still able to attach to host cells, but lost its ability to invade the cytoplasm. Recognition of pathogen-associated molecular patterns such as pili subunits by membrane-bound receptors facing the outside of the cell is not sufficient for NFκ-B induction.

  4. Strain-specific differences in pili formation and the interaction of Corynebacterium diphtheriae with host cells

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    Hensel Michael

    2010-10-01

    Full Text Available Abstract Background Corynebacterium diphtheriae, the causative agent of diphtheria, is well-investigated in respect to toxin production, while little is known about C. diphtheriae factors crucial for colonization of the host. In this study, we investigated strain-specific differences in adhesion, invasion and intracellular survival and analyzed formation of pili in different isolates. Results Adhesion of different C. diphtheriae strains to epithelial cells and invasion of these cells are not strictly coupled processes. Using ultrastructure analyses by atomic force microscopy, significant differences in macromolecular surface structures were found between the investigated C. diphtheriae strains in respect to number and length of pili. Interestingly, adhesion and pili formation are not coupled processes and also no correlation between invasion and pili formation was found. Using RNA hybridization and Western blotting experiments, strain-specific pili expression patterns were observed. None of the studied C. diphtheriae strains had a dramatic detrimental effect on host cell viability as indicated by measurements of transepithelial resistance of Detroit 562 cell monolayers and fluorescence microscopy, leading to the assumption that C. diphtheriae strains might use epithelial cells as an environmental niche supplying protection against antibodies and macrophages. Conclusions The results obtained suggest that it is necessary to investigate various isolates on a molecular level to understand and to predict the colonization process of different C. diphtheriae strains.

  5. Diphtheria-like illness in a fully immunised child caused by Corynebacterium pseudodiphtheriticum

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    V A Indumathi

    2014-01-01

    Full Text Available Corynebacterium pseudodiphtheriticum is a common commensal flora of the upper respiratory tract in humans. Though the pathogenicity of C. pseudodiphtheriticum is not rare, its role as an opportunistic pathogen is mainly limited to the lower respiratory tract, particularly in patients with underlying systemic conditions or immune-compromisation. We hereby present the first case of C. pseudodiphtheriticum causing diphtheria-like illness affecting the upper respiratory tract of a 6-year-old fully immunised otherwise healthy child. In countries with very low incidence of diphtheria, C. pseudodiphtheriticum should be included in differential diagnosis for a child presenting with diphtheria-like illness. Simple, rapid screening tests should be used to differentiate it from C. diphtheriae and hence, to prevent unnecessary concern in community.

  6. [Adhesion of corynebacterium diphtheriae: the role of surface structures and formation mechanism].

    Science.gov (United States)

    Kharseeva, G G; Alieva, A A

    2014-01-01

    The paper is devoted to the study of surface structures including pili (fimbriae) 67-72p surface protein, DIP 1281 surface protein, lipoarabinomannan CdiLAM and their role in the adhesion and colonization of the mucous membrane of the throat by Corynebacterium diphtheriae. A description is offered for the main stages in the adhesion process of diphtheria causative agent and the ability of its adhesins to stimulate the effect of innate and acquired immunity factors. The paper stresses prospectiveness of the development of vaccines forming immunoprotection of the organism against adhesive activity of C. diphtheriae and also preventing their colonization and reproduction. That would facilitate a solution for the problem of diphtheria carrier state, which cannot be solved using the existing means of preventive vaccination.

  7. Microbiological changes and diversity in autochthonous non-toxigenic Corynebacterium diphtheriae isolated in France.

    Science.gov (United States)

    Farfour, E; Badell, E; Dinu, S; Guillot, S; Guiso, N

    2013-10-01

    Autochtonous toxigenic Corynebacterium diphtheriae have disappeared in mainland France, but non-toxigenic C. diphtheriae are still circulating. Using phenotypic and molecular tools, we retrospectively characterized 103 non-toxigenic C. diphtheriae collected in mainland France and highlight several changes. The proportion of C. diphtheriae belfanti increased between 1977 and 2011 and it is the most frequent biotype recovered in recent years. Resistance to ciprofloxacin has increased and most isolates with decreased sensitivity belong to the belfanti biotype. Using multilocus sequence typing, we demonstrate that French isolates are distributed in a large number of sequence types and identify three distinct lineages. C. diphtheriae mitis and gravis form lineage I while C. diphtheriae belfanti forms lineages II and III. Almost all isolates of lineage II are part of a unique clonal complex or are very close to it. Most French isolates have a dtxR sequence homologous to that of toxigenic isolates, suggesting that if lyzogenised by a corynephage, they can express diphtheria toxin.

  8. Evolution, epidemiology and diversity of Corynebacterium diphtheriae: New perspectives on an old foe.

    Science.gov (United States)

    Sangal, Vartul; Hoskisson, Paul A

    2016-09-01

    Diphtheria is a debilitating disease caused by toxigenic Corynebacterium diphtheriae strains and has been effectively controlled by the toxoid vaccine, yet several recent outbreaks have been reported across the globe. Moreover, non-toxigenic C. diphtheriae strains are emerging as a major global health concern by causing severe pharyngitis and tonsillitis, endocarditis, septic arthritis and osteomyelitis. Molecular epidemiological investigations suggest the existence of outbreak-associated clones with multiple genotypes circulating around the world. Evolution and pathogenesis appears to be driven by recombination as major virulence factors, including the tox gene and pilus gene clusters, are found within genomic islands that appear to be mobile between strains. The number of pilus gene clusters and variation introduced by gain or loss of gene function correlate with the variable adhesive and invasive properties of C. diphtheriae strains. Genomic variation does not support the separation of C. diphtheriae strains into biovars which correlates well with findings of studies based on multilocus sequence typing. Genomic analyses of a relatively small number of strains also revealed a recombination driven diversification of strains within a sequence type and indicate a wider diversity among C. diphtheriae strains than previously appreciated. This suggests that there is a need for increased effort from the scientific community to study C. diphtheriae to help understand the genomic diversity and pathogenicity within the population of this important human pathogen.

  9. A lack of genetic basis for biovar differentiation in clinically important Corynebacterium diphtheriae from whole genome sequencing.

    Science.gov (United States)

    Sangal, Vartul; Burkovski, Andreas; Hunt, Alison C; Edwards, Becky; Blom, Jochen; Hoskisson, Paul A

    2014-01-01

    The differentiation of clinically important Corynebacterium diphtheriae into specific biovars is complex and phylogenetically unclear. Comparative genomic analyses of 17 strains indicate that the division of C. diphtheriae into different biovars does not correlate with the variation in the gene content in the relevant metabolic categories that are potentially involved in the biovar discrimination. The biochemical separation is also not supported by phylogenetic analyses, suggesting molecular methods of typing C. diphtheriae strains should be adopted much more widely.

  10. Characterization of DIP0733, a multi-functional virulence factor of Corynebacterium diphtheriae.

    Science.gov (United States)

    Antunes, Camila Azevedo; Sanches dos Santos, Louisy; Hacker, Elena; Köhler, Stefanie; Bösl, Korbinian; Ott, Lisa; de Luna, Maria das Graças; Hirata, Raphael; Azevedo, Vasco Ariston de Carvalho; Mattos-Guaraldi, Ana-Luíza; Burkovski, Andreas

    2015-03-01

    Corynebacterium diphtheriae is typically recognized as an extracellular pathogen. However, a number of studies revealed its ability to invade epithelial cells, indicating a more complex pathogen-host interaction. The molecular mechanisms controlling and facilitating internalization of Cor. diphtheriae are poorly understood. In this study, we investigated the role of DIP0733 as virulence factor to elucidate how it contributes to the process of pathogen-host cell interaction. Based on in vitro experiments, it was suggested recently that the DIP0733 protein might be involved in adhesion, invasion of epithelial cells and induction of apoptosis. A corresponding Cor. diphtheriae mutant strain generated in this study was attenuated in its ability to colonize and kill the host in a Caenorhabditis elegans infection model system. Furthermore, the mutant showed an altered adhesion pattern and a drastically reduced ability to adhere and invade epithelial cells. Subsequent experiments showed an influence of DIP0733 on binding of Cor. diphtheriae to extracellular matrix proteins such as collagen and fibronectin. Furthermore, based on its fibrinogen-binding activity, DIP0733 may play a role in avoiding recognition of Cor. diphtheriae by the immune system. In summary, our findings support the idea that DIP0733 is a multi-functional virulence factor of Cor. diphtheriae.

  11. Multilocus sequence typing identifies evidence for recombination and two distinct lineages of Corynebacterium diphtheriae.

    Science.gov (United States)

    Bolt, Frances; Cassiday, Pamela; Tondella, Maria Lucia; Dezoysa, Aruni; Efstratiou, Androulla; Sing, Andreas; Zasada, Aleksandra; Bernard, Kathryn; Guiso, Nicole; Badell, Edgar; Rosso, Marie-Laure; Baldwin, Adam; Dowson, Christopher

    2010-11-01

    We describe the development of a multilocus sequence typing (MLST) scheme for Corynebacterium diphtheriae, the causative agent of the potentially fatal upper respiratory disease diphtheria. Global changes in diphtheria epidemiology are highlighted by the recent epidemic in the former Soviet Union (FSU) and also by the emergence of nontoxigenic strains causing atypical disease. Although numerous techniques have been developed to characterize C. diphtheriae, their use is hindered by limited portability and, in some instances, poor reproducibility. One hundred fifty isolates from 18 countries and encompassing a period of 50 years were analyzed by multilocus sequence typing (MLST). Strain discrimination was in accordance with previous ribotyping data, and clonal complexes associated with disease outbreaks were clearly identified by MLST. The data produced are portable, reproducible, and unambiguous. The MLST scheme described provides a valuable tool for monitoring and characterizing endemic and epidemic C. diphtheriae strains. Furthermore, multilocus sequence analysis of the nucleotide data reveals two distinct lineages within the population of C. diphtheriae examined, one of which is composed exclusively of biotype belfanti isolates and the other of multiple biotypes.

  12. Multilocus sequence types of invasive Corynebacterium diphtheriae isolated in the Rio de Janeiro urban area, Brazil.

    Science.gov (United States)

    Viguetti, S Z; Pacheco, L G C; Santos, L S; Soares, S C; Bolt, F; Baldwin, A; Dowson, C G; Rosso, M L; Guiso, N; Miyoshi, A; Hirata, R; Mattos-Guaraldi, A L; Azevedo, V

    2012-04-01

    Invasive infections caused by Corynebacterium diphtheriae in vaccinated and non-vaccinated individuals have been reported increasingly. In this study we used multilocus sequence typing (MLST) to study genetic relationships between six invasive strains of this bacterium isolated solely in the urban area of Rio de Janeiro, Brazil, during a 10-year period. Of note, all the strains rendered negative results in PCR reactions for the tox gene, and four strains presented an atypical sucrose-fermenting ability. Five strains represented new sequence types. MLST results did not support the hypothesis that invasive (sucrose-positive) strains of C. diphtheriae are part of a single clonal complex. Instead, one of the main findings of the study was that such strains can be normally found in clonal complexes with strains related to non-invasive disease. Comparative analyses with C. diphtheriae isolated in different countries provided further information on the geographical circulation of some sequence types.

  13. Potential pathogenic role of aggregative-adhering Corynebacterium diphtheriae of different clonal groups in endocarditis.

    Science.gov (United States)

    Hirata Jr, R; Pereira, G A; Filardy, A A; Gomes, D L R; Damasco, P V; Rosa, A C P; Nagao, P E; Pimenta, F P; Mattos-Guaraldi, A L

    2008-11-01

    Invasive diseases caused by Corynebacterium diphtheriae have been described increasingly. Several reports indicate the destructive feature of endocarditis attributable to nontoxigenic strains. However, few reports have dealt with the pathogenicity of invasive strains. The present investigation demonstrates a phenotypic trait that may be used to identify potentially invasive strains. The study also draws attention to clinical and microbiological aspects observed in 5 cases of endocarditis due to C. diphtheriae that occurred outside Europe. Four cases occurred in female school-age children (7-14 years) treated at different hospitals in Rio de Janeiro, Brazil. All patients developed other complications including septicemia, renal failure and/or arthritis. Surgical treatment was performed on 2 patients for valve replacement. Lethality was observed in 40% of the cases. Microorganisms isolated from 5 blood samples and identified as C. diphtheriae subsp mitis (N = 4) and C. diphtheriae subsp gravis (N = 1) displayed an aggregative adherence pattern to HEp-2 cells and identical one-dimensional SDS-PAGE protein profiles. Aggregative-adhering invasive strains of C. diphtheriae showed 5 distinct RAPD profiles. Despite the clonal diversity, all 5 C. diphtheriae invasive isolates seemed to display special bacterial adhesive properties that may favor blood-barrier disruption and systemic dissemination of bacteria. In conclusion, blood isolates from patients with endocarditis exhibited a unique adhering pattern, suggesting a pathogenic role of aggregative-adhering C. diphtheriae of different clones in endocarditis. Accordingly, the aggregative-adherence pattern may be used as an indication of some invasive potential of C. diphtheriae strains.

  14. Potential pathogenic role of aggregative- adhering Corynebacterium diphtheriae of different clonal groups in endocarditis

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    R. Hirata Jr.

    2008-11-01

    Full Text Available Invasive diseases caused by Corynebacterium diphtheriae have been described increasingly. Several reports indicate the destructive feature of endocarditis attributable to nontoxigenic strains. However, few reports have dealt with the pathogenicity of invasive strains. The present investigation demonstrates a phenotypic trait that may be used to identify potentially invasive strains. The study also draws attention to clinical and microbiological aspects observed in 5 cases of endocarditis due to C. diphtheriae that occurred outside Europe. Four cases occurred in female school-age children (7-14 years treated at different hospitals in Rio de Janeiro, Brazil. All patients developed other complications including septicemia, renal failure and/or arthritis. Surgical treatment was performed on 2 patients for valve replacement. Lethality was observed in 40% of the cases. Microorganisms isolated from 5 blood samples and identified as C. diphtheriae subsp mitis (N = 4 and C. diphtheriae subsp gravis (N = 1 displayed an aggregative adherence pattern to HEp-2 cells and identical one-dimensional SDS-PAGE protein profiles. Aggregative-adhering invasive strains of C. diphtheriae showed 5 distinct RAPD profiles. Despite the clonal diversity, all 5 C. diphtheriae invasive isolates seemed to display special bacterial adhesive properties that may favor blood-barrier disruption and systemic dissemination of bacteria. In conclusion, blood isolates from patients with endocarditis exhibited a unique adhering pattern, suggesting a pathogenic role of aggregative-adhering C. diphtheriae of different clones in endocarditis. Accordingly, the aggregative-adherence pattern may be used as an indication of some invasive potential of C. diphtheriae strains.

  15. Genome organization and pathogenicity of Corynebacterium diphtheriae C7(-) and PW8 strains.

    Science.gov (United States)

    Iwaki, Masaaki; Komiya, Takako; Yamamoto, Akihiko; Ishiwa, Akiko; Nagata, Noriyo; Arakawa, Yoshichika; Takahashi, Motohide

    2010-09-01

    Corynebacterium diphtheriae is the causative agent of diphtheria. In 2003, the complete genomic nucleotide sequence of an isolate (NCTC13129) from a large outbreak in the former Soviet Union was published, in which the presence of 13 putative pathogenicity islands (PAIs) was demonstrated. In contrast, earlier work on diphtheria mainly employed the C7(-) strain for genetic analysis; therefore, current knowledge of the molecular genetics of the bacterium is limited to that strain. However, genomic information on the NCTC13129 strain has scarcely been compared to strain C7(-). Another important C. diphtheriae strain is Park-Williams no. 8 (PW8), which has been the only major strain used in toxoid vaccine production and for which genomic information also is not available. Here, we show by comparative genomic hybridization that at least 37 regions from the reference genome, including 11 of the 13 PAIs, are considered to be absent in the C7(-) genome. Despite this, the C7(-) strain still retained signs of pathogenicity, showing a degree of adhesion to Detroit 562 cells, as well as the formation of and persistence in abscesses in animal skin comparable to that of the NCTC13129 strain. In contrast, the PW8 strain, suggested to lack 14 genomic regions, including 3 PAIs, exhibited more reduced signs of pathogenicity. These results, together with great diversity in the presence of the 37 genomic regions among various C. diphtheriae strains shown by PCR analyses, suggest great heterogeneity of this pathogen, not only in genome organization, but also in pathogenicity.

  16. [The sensitivity to antibiotics of biofilm cultures of toxigenic strains Corynebacterium diphtheriae].

    Science.gov (United States)

    Frolova, Ya N; Kharseyeva, G G; Mironov, A Yu

    2014-06-01

    The article presents analysis of sensitivity to antibacterial preparations of typical and biofilm culture of museum strain of Corynebacterium diphtheriae gravis tox+ SV-665. The strain was obtained from the L.A. Tarasevitch state research institute of standardization and control of medical biological preparations. The second strain C. diphtheriaecirculates gravis tox+ circulates in population of the Rostov oblast and it was recovered from patient with diagnosis of "localized form of diphtheria" by bacteriologic laboratory "1002 CGSEN SKVO" of Rostov-on-Don. The week and month biofilm cultures of both strains of C. diphtheriae gravis tox+ were used. The sensitivity to antibacterial preparations of typical and biofilm cultures of museum and circulating in population strains of agent of diphtheria were detected using minimal suppressing concentration by technique of serial dilutions in fluid growth medium. It is demonstrated that the most effective in respect of C. diphtheriae are such preparations as cefotaxinum, gentamycinum, lincomycin, canamycin and cefasolin. The sensitivity of pathogen in composition of biofilm to these preparations has no changes.

  17. Toxigenic Corynebacterium ulcerans isolated from a hunting dog and its diphtheria toxin antibody titer.

    Science.gov (United States)

    Katsukawa, Chihiro; Komiya, Takako; Umeda, Kaoru; Goto, Minami; Yanai, Tokuma; Takahashi, Motohide; Yamamoto, Akihiko; Iwaki, Masaaki

    2016-03-01

    Toxigenic Corynebacterium ulcerans is a zoonotic pathogen that produces diphtheria toxin and causes a diphtheria-like illness in humans. The organism is known to infect and circulate among dogs, which can then transmit it to humans. Furthermore, previous studies have found that C. ulcerans is carried by wild animals, including game animals. In the present study, we tested hunting and companion dogs for the presence of toxigenic C. ulcerans and succeeded in isolating the bacterium from a hunting dog. Moreover, several hunting dogs had serum diphtheria antitoxin titers that were higher than the titers required for protection in humans, suggesting a history of exposure to toxigenic Corynebacterium strains. Notably, ribotyping, pulsed-field gel electrophoresis and tox gene sequencing demonstrated that the isolate from the hunting dog clustered with previously characterized C. ulcerans strains isolated from wild animals, as opposed to groups of isolates from humans and companion dogs. Interestingly, the wild animal cluster also contains an isolate from an outdoor breeding dog, which could have formed a bridge between isolates from wild animals and those from companion dogs. The results presented herein provide insight into the mechanism by which the zoonotic pathogen C. ulcerans circulates among wild animals, hunting and companion dogs, and humans.

  18. Screening for Corynebacterium diphtheriae and Corynebacterium ulcerans in patients with upper respiratory tract infections 2007-2008: a multicentre European study.

    LENUS (Irish Health Repository)

    Wagner, K S

    2011-04-01

    Diphtheria is now rare in most European countries but, when cases do arise, the case fatality rate is high (5-10%). Because few countries continue to routinely screen for the causative organisms of diphtheria, the extent to which they are circulating amongst different European populations is largely unknown. During 2007-2008, ten European countries each screened between 968 and 8551 throat swabs from patients with upper respiratory tract infections. Six toxigenic strains of Corynebacterium diphtheriae were identified: two from symptomatic patients in Latvia (the country with the highest reported incidence of diphtheria in the European Union) and four from Lithuania (two cases, two carriers); the last reported case of diphtheria in Lithuania was in 2002. Carriage rates of non-toxigenic organisms ranged from 0 (Bulgaria, Finland, Greece, Ireland, Italy) to 4.0 per 1000 (95% CI 2.0-7.1) in Turkey. A total of 28 non-toxigenic strains were identified during the study (26 C. diphtheriae, one Corynebacterium ulcerans, one Corynebacterium pseudotuberculosis). The non-toxigenic C. ulcerans strain was isolated from the UK, the country with the highest reported incidence of cases due to C. ulcerans. Of the eleven ribotypes detected, Cluj was seen most frequently in the non-toxigenic isolates and, amongst toxigenic isolates, the major epidemic clone, Sankt-Petersburg, is still in circulation. Isolation of toxigenic C. diphtheriae and non-toxigenic C. diphtheriae and C. ulcerans in highly-vaccinated populations highlights the need to maintain microbiological surveillance, laboratory expertise and an awareness of these organisms amongst public health specialists, microbiologists and clinicians.

  19. Usefulness of 16S rDNA sequencing for the diagnosis of infective endocarditis caused by Corynebacterium diphtheriae.

    Science.gov (United States)

    Pathipati, Padmaja; Menon, Thangam; Kumar, Naveen; Francis, Thara; Sekar, Prem; Cherian, Kotturathu Mammen

    2012-08-01

    We report a rare case of infective endocarditis caused by Corynebacterium diphtheriae in an 8-year-old boy, 2 years after a right ventricular outflow tract reconstruction with a bovine Contegra valved conduit. The patient recovered well after an RV-PA conduit enblock explantation and replacement with an aortic homograft with antibiotic treatment. All bacteriological cultures of excised tissue and blood were negative. The aetiological agent was identified as C. diphtheriae subsp. gravis by 16s rDNA sequencing.

  20. Identification and functional characterization of the NanH extracellular sialidase from Corynebacterium diphtheriae.

    Science.gov (United States)

    Kim, Seonghun; Oh, Doo-Byoung; Kwon, Ohsuk; Kang, Hyun Ah

    2010-04-01

    Corynebacterium diphtheriae, a pathogenic Gram-positive bacterium, contains sialic acids on its cell surface, but no genes related to sialic acid decoration or metabolism have been reported in C. diphtheriae. In the present study, we have identified a putative sialidase gene, nanH, from C. diphtheriae KCTC3075 and characterized its product for enzyme activity. Interestingly, the recombinant NanH protein was secreted as a catalytically active sialidase into the periplasmic space in Escherichia coli, while the short region at its C-terminus was truncated by proteolysis. We reconstructed a truncated NanH protein (His(6)-NanH(DeltaN)) devoid of its signal sequence as a mature enzyme fused with the 6xHis tag at the N-terminal region. The purified His(6)-NanH(DeltaN) can cleave alpha-2,3- and alpha-2,6-linked sialic acid from sialic acid-containing substrates. In addition, even though the efficiency was low, the recombinant His(6)-NanH(DeltaN) was able to catalyse the transfer of sialic acid using several sialoconjugates as donor, suggesting that the reversible nature of C. diphtheriae NanH can be used for the synthesis of sialyl oligosaccharides via transglycosylation reaction.

  1. Pangenomic study of Corynebacterium diphtheriae that provides insights into the genomic diversity of pathogenic isolates from cases of classical diphtheria, endocarditis, and pneumonia.

    Science.gov (United States)

    Trost, Eva; Blom, Jochen; Soares, Siomar de Castro; Huang, I-Hsiu; Al-Dilaimi, Arwa; Schröder, Jasmin; Jaenicke, Sebastian; Dorella, Fernanda A; Rocha, Flavia S; Miyoshi, Anderson; Azevedo, Vasco; Schneider, Maria P; Silva, Artur; Camello, Thereza C; Sabbadini, Priscila S; Santos, Cíntia S; Santos, Louisy S; Hirata, Raphael; Mattos-Guaraldi, Ana L; Efstratiou, Androulla; Schmitt, Michael P; Ton-That, Hung; Tauch, Andreas

    2012-06-01

    Corynebacterium diphtheriae is one of the most prominent human pathogens and the causative agent of the communicable disease diphtheria. The genomes of 12 strains isolated from patients with classical diphtheria, endocarditis, and pneumonia were completely sequenced and annotated. Including the genome of C. diphtheriae NCTC 13129, we herewith present a comprehensive comparative analysis of 13 strains and the first characterization of the pangenome of the species C. diphtheriae. Comparative genomics showed extensive synteny and revealed a core genome consisting of 1,632 conserved genes. The pangenome currently comprises 4,786 protein-coding regions and increases at an average of 65 unique genes per newly sequenced strain. Analysis of prophages carrying the diphtheria toxin gene tox revealed that the toxoid vaccine producer C. diphtheriae Park-Williams no. 8 has been lysogenized by two copies of the ω(tox)(+) phage, whereas C. diphtheriae 31A harbors a hitherto-unknown tox(+) corynephage. DNA binding sites of the tox-controlling regulator DtxR were detected by genome-wide motif searches. Comparative content analysis showed that the DtxR regulons exhibit marked differences due to gene gain, gene loss, partial gene deletion, and DtxR binding site depletion. Most predicted pathogenicity islands of C. diphtheriae revealed characteristics of horizontal gene transfer. The majority of these islands encode subunits of adhesive pili, which can play important roles in adhesion of C. diphtheriae to different host tissues. All sequenced isolates contain at least two pilus gene clusters. It appears that variation in the distributed genome is a common strategy of C. diphtheriae to establish differences in host-pathogen interactions.

  2. Pangenomic Study of Corynebacterium diphtheriae That Provides Insights into the Genomic Diversity of Pathogenic Isolates from Cases of Classical Diphtheria, Endocarditis, and Pneumonia

    Science.gov (United States)

    Trost, Eva; Blom, Jochen; de Castro Soares, Siomar; Huang, I-Hsiu; Al-Dilaimi, Arwa; Schröder, Jasmin; Jaenicke, Sebastian; Dorella, Fernanda A.; Rocha, Flavia S.; Miyoshi, Anderson; Azevedo, Vasco; Schneider, Maria P.; Silva, Artur; Camello, Thereza C.; Sabbadini, Priscila S.; Santos, Cíntia S.; Santos, Louisy S.; Hirata, Raphael; Mattos-Guaraldi, Ana L.; Efstratiou, Androulla; Schmitt, Michael P.; Ton-That, Hung

    2012-01-01

    Corynebacterium diphtheriae is one of the most prominent human pathogens and the causative agent of the communicable disease diphtheria. The genomes of 12 strains isolated from patients with classical diphtheria, endocarditis, and pneumonia were completely sequenced and annotated. Including the genome of C. diphtheriae NCTC 13129, we herewith present a comprehensive comparative analysis of 13 strains and the first characterization of the pangenome of the species C. diphtheriae. Comparative genomics showed extensive synteny and revealed a core genome consisting of 1,632 conserved genes. The pangenome currently comprises 4,786 protein-coding regions and increases at an average of 65 unique genes per newly sequenced strain. Analysis of prophages carrying the diphtheria toxin gene tox revealed that the toxoid vaccine producer C. diphtheriae Park-Williams no. 8 has been lysogenized by two copies of the ωtox+ phage, whereas C. diphtheriae 31A harbors a hitherto-unknown tox+ corynephage. DNA binding sites of the tox-controlling regulator DtxR were detected by genome-wide motif searches. Comparative content analysis showed that the DtxR regulons exhibit marked differences due to gene gain, gene loss, partial gene deletion, and DtxR binding site depletion. Most predicted pathogenicity islands of C. diphtheriae revealed characteristics of horizontal gene transfer. The majority of these islands encode subunits of adhesive pili, which can play important roles in adhesion of C. diphtheriae to different host tissues. All sequenced isolates contain at least two pilus gene clusters. It appears that variation in the distributed genome is a common strategy of C. diphtheriae to establish differences in host-pathogen interactions. PMID:22505676

  3. Invasion of endothelial cells and arthritogenic potential of endocarditis-associated Corynebacterium diphtheriae.

    Science.gov (United States)

    Peixoto, Renata Stavracakis; Pereira, Gabriela Andrade; Sanches dos Santos, Louisy; Rocha-de-Souza, Cláudio Marcos; Gomes, Débora Leandro Rama; Silva Dos Santos, Cintia; Werneck, Lucia Maria Correa; Dias, Alexandre Alves de Souza de Oliveira; Hirata, Raphael; Nagao, Prescilla Emy; Mattos-Guaraldi, Ana Luíza

    2014-03-01

    Although infection by Corynebacterium diphtheriae is a model of extracellular mucosal pathogenesis, different clones have been also associated with invasive infections such as sepsis, endocarditis, septic arthritis and osteomyelitis. The mechanisms that promote C. diphtheriae infection and haematogenic dissemination need further investigation. In this study we evaluated the association and invasion mechanisms with human umbilical vein endothelial cells (HUVECs) and experimental arthritis in mice of endocarditis-associated strains and control non-invasive strains. C. diphtheriae strains were able to adhere to and invade HUVECs at different levels. The endocarditis-associated strains displayed an aggregative adherence pattern and a higher number of internalized viable cells in HUVECs. Transmission electron microscopy (TEM) analysis revealed intracellular bacteria free in the cytoplasm and/or contained in a host-membrane-confined compartment as single micro-organisms. Data showed bacterial internalization dependent on microfilament and microtubule stability and involvement of protein phosphorylation in the HUVEC signalling pathway. A high number of affected joints and high arthritis index in addition to the histopathological features indicated a strain-dependent ability of C. diphtheriae to cause severe polyarthritis. A correlation between the arthritis index and increased systemic levels of IL-6 and TNF-α was observed for endocarditis-associated strains. In conclusion, higher incidence of potential mechanisms by which C. diphtheriae may access the bloodstream through the endothelial barrier and stimulate the production of pro-inflammatory cytokines such as IL-6 and TNF-α, in addition to the ability to affect the joints and induce arthritis through haematogenic spread are thought to be related to the pathogenesis of endocarditis-associated strains.

  4. Differential Chemical Protection of Mammalian Cells from the Exotoxins of ’Corynebacterium diphtheriae’ and ’Pseudomonas aeruginosa’,

    Science.gov (United States)

    Many drugs or chemicals had markedly different effects on the cytotoxicity induced by Pseudomonas aeruginosa exotoxin A (PE) or Corynebacterium ... diphtheriae exotoxin (DE). The glycolytic inhibitor NaF protected cells from DE but potentiated the cytotoxicity of PE. Another energy inhibitor, salicylic

  5. Regulation and activity of a zinc uptake regulator, Zur, in Corynebacterium diphtheriae.

    Science.gov (United States)

    Smith, Kelsy F; Bibb, Lori A; Schmitt, Michael P; Oram, Diana M

    2009-03-01

    Regulation of metal ion homeostasis is essential to bacterial cell survival, and in most species it is controlled by metal-dependent transcriptional regulators. In this study, we describe a Corynebacterium diphtheriae ferric uptake regulator-family protein, Zur, that controls expression of genes involved in zinc uptake. By measuring promoter activities and mRNA levels, we demonstrate that Zur represses transcription of three genes (zrg, cmrA, and troA) in zinc-replete conditions. All three of these genes have similarity to genes involved in zinc uptake. Transcription of zrg and cmrA was also shown to be regulated in response to iron and manganese, respectively, by mechanisms that are independent of Zur. We demonstrate that the activity of the zur promoter is slightly decreased under low zinc conditions in a process that is dependent on Zur itself. This regulation of zur transcription is distinctive and has not yet been described for any other zur. An adjacent gene, predicted to encode a metal-dependent transcriptional regulator in the ArsR/SmtB family, is transcribed from a separate promoter whose activity is unaffected by Zur. A C. diphtheriae zur mutant was more sensitive to peroxide stress, which suggests that zur has a role in protecting the bacterium from oxidative damage. Our studies provide the first evidence of a zinc specific transcriptional regulator in C. diphtheriae and give new insights into the intricate regulatory network responsible for regulating metal ion concentrations in this toxigenic human pathogen.

  6. Pathogenic properties of a Corynebacterium diphtheriae strain isolated from a case of osteomyelitis.

    Science.gov (United States)

    Peixoto, Renata Stavracakis; Hacker, Elena; Antunes, Camila Azevedo; Weerasekera, Dulanthi; Dias, Alexandre Alves de Souza de Oliveira; Martins, Carlos Alberto; Hirata, Raphael; Santos, Kátia Regina Netto Dos; Burkovski, Andreas; Mattos-Guaraldi, Ana Luíza

    2016-11-01

    Corynebacterium diphtheriae is typically recognized as a colonizer of the upper respiratory tract (respiratory diphtheria) and the skin (cutaneous diphtheria). However, different strains of Corynebacteriumdiphtheriae can also cause invasive infections. In this study, the characterization of a non-toxigenic Corynebacteriumdiphtheriae strain (designated BR-INCA5015) isolated from osteomyelitis in the frontal bone of a patient with adenoid cystic carcinoma was performed. Pathogenic properties of the strain BR-INCA5015 were tested in a Caenorhabditis elegans survival assay showing strong colonization and killing by this strain. Survival rates of 3.8±2.7 %, 33.6±7.3 % and 0 % were observed for strains ATCC 27010T, ATCC 27012 and BR-INCA5015, respectively, at day 7. BR-INCA5015 was able to colonize epithelial cells, showing elevated capacity to adhere to and survive within HeLa cells compared to other Corynebacteriumdiphtheriae isolates. Intracellular survival in macrophages (THP-1 and RAW 264.7) was significantly higher compared to control strains ATCC 27010T (non-toxigenic) and ATCC 27012 (toxigenic). Furthermore, the ability of BR-INCA5015 to induce osteomyelitis was confirmed by in vivo assay using Swiss Webster mice.

  7. A PCR for dtxR gene: application to diagnosis of non-toxigenic and toxigenic Corynebacterium diphtheriae.

    Science.gov (United States)

    Pimenta, Fabricia P; Matias, Gisele A M; Pereira, Gabriela A; Camello, Thereza C F; Alves, Gabriela B; Rosa, Ana C P; Hirata, Raphael; Mattos-Guaraldi, Ana L

    2008-06-01

    The significant rise in the percentage of adults susceptible to diphtheria and the emergence of non-toxigenic Corynebacterium diphtheriae strains as the causative agent of endocarditis and other systemic infections emphasize the need for alternative laboratory diagnostic procedures. In this study, for the first time, the value of a species-specific PCR assay that targets the dtxR gene is documented as a procedure for differentiating C. diphtheriae from Corynebacterium-like colonies. The results of the PCR-dtxR were all positive for 91 C. diphtheriae (54 non-toxigenic and 37 toxigenic) strains. PCR-dtxR completely correlated with the standard biochemical and commercial identification for all C. diphtheriae strains tested. Conversely, the PCR-dtxR results were negative in 100% of the 111 non-diphtherial Gram-positive rod strains obtained during identification procedures in a hospital laboratory. Thus, the PCR-dtxR assay emerged as viable, cost-effective screening method for C. diphtheriae laboratory identification.

  8. Analysis of novel iron-regulated, surface-anchored hemin-binding proteins in Corynebacterium diphtheriae.

    Science.gov (United States)

    Allen, Courtni E; Burgos, Jonathan M; Schmitt, Michael P

    2013-06-01

    Corynebacterium diphtheriae utilizes hemin and hemoglobin (Hb) as iron sources during growth in iron-depleted environments, and recent studies have shown that the surface-exposed HtaA protein binds both hemin and Hb and also contributes to the utilization of hemin iron. Conserved (CR) domains within HtaA and in the associated hemin-binding protein, HtaB, are required for the ability to bind hemin and Hb. In this study, we identified and characterized two novel genetic loci in C. diphtheriae that encode factors that bind hemin and Hb. Both genetic systems contain two-gene operons that are transcriptionally regulated by DtxR and iron. The gene products of these operons are ChtA-ChtB and ChtC-CirA (previously DIP0522-DIP0523). The chtA and chtB genes are carried on a putative composite transposon associated with C. diphtheriae isolates that dominated the diphtheria outbreak in the former Soviet Union in the 1990s. ChtA and ChtC each contain a single N-terminal CR domain and exhibit significant sequence similarity to each other but only limited similarity with HtaA. The chtB and htaB gene products exhibited a high level of sequence similarity throughout their sequences, and both proteins contain a single CR domain. Whole-cell binding studies as well as protease analysis indicated that all four of the proteins encoded by these two operons are surface exposed, which is consistent with the presence of a transmembrane segment in their C-terminal regions. ChtA, ChtB, and ChtC are able to bind hemin and Hb, with ChtA showing the highest affinity. Site-directed mutagenesis showed that specific tyrosine residues within the ChtA CR domain were critical for hemin and Hb binding. Hemin iron utilization assays using various C. diphtheriae mutants indicate that deletion of the chtA-chtB region and the chtC gene has no affect on the ability of C. diphtheriae to use hemin or Hb as iron sources; however, a chtB htaB double mutant exhibits a significant decrease in hemin iron use

  9. Characterization of OxyR as a negative transcriptional regulator that represses catalase production in Corynebacterium diphtheriae.

    Directory of Open Access Journals (Sweden)

    Ju-Sim Kim

    Full Text Available Corynebacterium diphtheriae and Corynebacterium glutamicum each have one gene (cat encoding catalase. In-frame Δcat mutants of C. diphtheriae and C. glutamicum were hyper-sensitive to growth inhibition and killing by H(2O(2. In C. diphtheriae C7(β, both catalase activity and cat transcription decreased ~2-fold during transition from exponential growth to early stationary phase. Prototypic OxyR in Escherichia coli senses oxidative stress and it activates katG transcription and catalase production in response to H(2O(2. In contrast, exposure of C. diphtheriae C7(β to H(2O(2 did not stimulate transcription of cat. OxyR from C. diphtheriae and C. glutamicum have 52% similarity with E. coli OxyR and contain homologs of the two cysteine residues involved in H(2O(2 sensing by E. coli OxyR. In-frame ΔoxyR deletion mutants of C. diphtheriae C7(β, C. diphtheriae NCTC13129, and C. glutamicum were much more resistant than their parental wild type strains to growth inhibition by H(2O(2. In the C. diphtheriae C7(β ΔoxyR mutant, cat transcripts were about 8-fold more abundant and catalase activity was about 20-fold greater than in the C7(β wild type strain. The oxyR gene from C. diphtheriae or C. glutamicum, but not from E. coli, complemented the defect in ΔoxyR mutants of C. diphtheriae and C. glutamicum and decreased their H(2O(2 resistance to the level of their parental strains. Gel-mobility shift, DNaseI footprint, and primer extension assays showed that purified OxyR from C. diphtheriae C7(β bound, in the presence or absence of DTT, to a sequence in the cat promoter region that extends from nucleotide position -55 to -10 with respect to the +1 nucleotide in the cat ORF. These results demonstrate that OxyR from C. diphtheriae or C. glutamicum functions as a transcriptional repressor of the cat gene by a mechanism that is independent of oxidative stress induced by H(2O(2.

  10. Characterization of OxyR as a negative transcriptional regulator that represses catalase production in Corynebacterium diphtheriae.

    Science.gov (United States)

    Kim, Ju-Sim; Holmes, Randall K

    2012-01-01

    Corynebacterium diphtheriae and Corynebacterium glutamicum each have one gene (cat) encoding catalase. In-frame Δcat mutants of C. diphtheriae and C. glutamicum were hyper-sensitive to growth inhibition and killing by H(2)O(2). In C. diphtheriae C7(β), both catalase activity and cat transcription decreased ~2-fold during transition from exponential growth to early stationary phase. Prototypic OxyR in Escherichia coli senses oxidative stress and it activates katG transcription and catalase production in response to H(2)O(2). In contrast, exposure of C. diphtheriae C7(β) to H(2)O(2) did not stimulate transcription of cat. OxyR from C. diphtheriae and C. glutamicum have 52% similarity with E. coli OxyR and contain homologs of the two cysteine residues involved in H(2)O(2) sensing by E. coli OxyR. In-frame ΔoxyR deletion mutants of C. diphtheriae C7(β), C. diphtheriae NCTC13129, and C. glutamicum were much more resistant than their parental wild type strains to growth inhibition by H(2)O(2). In the C. diphtheriae C7(β) ΔoxyR mutant, cat transcripts were about 8-fold more abundant and catalase activity was about 20-fold greater than in the C7(β) wild type strain. The oxyR gene from C. diphtheriae or C. glutamicum, but not from E. coli, complemented the defect in ΔoxyR mutants of C. diphtheriae and C. glutamicum and decreased their H(2)O(2) resistance to the level of their parental strains. Gel-mobility shift, DNaseI footprint, and primer extension assays showed that purified OxyR from C. diphtheriae C7(β) bound, in the presence or absence of DTT, to a sequence in the cat promoter region that extends from nucleotide position -55 to -10 with respect to the +1 nucleotide in the cat ORF. These results demonstrate that OxyR from C. diphtheriae or C. glutamicum functions as a transcriptional repressor of the cat gene by a mechanism that is independent of oxidative stress induced by H(2)O(2).

  11. Microbiological and molecular characterization of Corynebacterium diphtheriae isolated in Algeria between 1992 and 2015.

    Science.gov (United States)

    Benamrouche, N; Hasnaoui, S; Badell, E; Guettou, B; Lazri, M; Guiso, N; Rahal, K

    2016-12-01

    The objectives of this study were to undertake the microbiological and molecular characterization of Corynebacterium diphtheriae isolates collected in Algeria during epidemic and post-epidemic periods between 1992 and 2015. Microbiological characterization includes the determination of biotype and toxigenicity status using phenotypic and genotypic methods. Antimicrobial susceptibility was determined by the E-test method. Molecular characterization was performed by multi-locus sequence typing. In total, there were 157 cases of C. diphtheriae isolates, 127 in patients with respiratory diphtheria and 30 with ozena. Isolates with a mitis biotype were predominant (122 out of 157; 77.7%) followed by belfanti (28 out of 157; 17.8%) and gravis biotype (seven out of 157; 4.5%). Toxigenic isolates were predominant in the period 1992-2006 (74 out of 134) whereas in the period 2007-2015, only non-toxigenic isolates circulated (23 out of 23). All 157 isolates were susceptible to erythromycin, gentamicin, vancomycin and cotrimoxazole. Reduced susceptibility to penicillin G, cefotaxime, tetracycline and chloramphenicol was detected in 90 (57.3%), 88 (56.1%), 112 (71.3%) and 90 (57.3%) isolates, respectively. Multi-locus sequence typing analysis indicates that sequence type 116 (ST-116) was the most frequent, with 65 out of 100 isolates analysed, in particular during the epidemic period 1992-1999 (57 out of 65 isolates). In the post-epidemic period, 2000-2015, 13 different sequence types were isolated. All belfanti isolates (ten out of 100 isolates) belonged to closely related sequence types grouped in a phylogenetically distinct eBurst group and were collected exclusively in ozena cases. In conclusion, the epidemic period was associated with ST-116 while the post-epidemic period was characterized by more diversity. Belfanti isolates are grouped in a phylogenetically distinct clonal complex.

  12. Similarity of rpoB gene sequences of sucrose-fermenting and non-fermenting Corynebacterium diphtheriae strains.

    Science.gov (United States)

    Hirata, R; Pacheco, L G; Soares, S C; Santos, L S; Moreira, L O; Sabbadini, P S; Santos, C S; Miyoshi, A; Azevedo, V A; Mattos-Guaraldi, A L

    2011-03-01

    During the last decades, the majority of Brazilian Corynebacterium diphtheriae isolates were shown to be capable to metabolize sucrose, sometimes leading to erroneous identification as a non-diphtheric Corynebacterium species. The sequencing of the polymorphic region of the RNA polymerase beta subunit-encoding gene (rpoB) is an important taxonomic tool for identification of corynebacteria. The present study aimed to investigate the rpoB gene polymorphic features of sucrose-fermenting and non sucrose-fermenting strains. The results showed that sucrose-fermenting strains presented rpoB gene polymorphic regions with more than 98% similarity with the sequences deposited in the gene bank corresponding to non sucrose-fermenting strains. Data indicate that sucrose-fermenting isolates may act as a variant of C. diphtheriae biotype mitis. In addition we alert that sucrose-fermenting strains should not be discarded as contaminants mainly in countries where the possibility of isolation of this variant is higher.

  13. Evidence of increased carriage of Corynebacterium spp. in healthy individuals with low antibody titres against diphtheria toxoid.

    Science.gov (United States)

    Bergamini, M; Fabrizi, P; Pagani, S; Grilli, A; Severini, R; Contini, C

    2000-08-01

    This study evaluated whether a correlation exists between carriage of corynebacteria and the lack of immunity to diphtheria toxoid. Samples of both nasal and pharyngeal secretions were taken from 500 apparently healthy subjects of both sexes and of all ages and inoculated onto Tinsdale's medium. A serum sample was also taken for ELISA test to determine the titre of diphtheria toxin antibodies. None of the subjects carried Corynebacterium diphtheriae. Ninety-three strains of Corynebacterium spp. were isolated from 93 subjects and 86 of these were classified to species or group level by biochemical tests. C. xerosis was the most common (25.8%) followed by C. pseudodiphthericum (16.1%), C. jeikeium and C. striatum (both 10.8%), and C. urealyticum (9.7%). Three other species accounted for approximately 20% of strains and seven were unclassified as biochemically atypical corynebacteria. Non-protective antibodies to diphtheria toxin were found in 80 of the 93 subjects and a strong statistical association was demonstrated between carriage of corynebacteria and non-protective levels of anti-toxin antibodies. The remaining 13 subjects had protective levels of antitoxin antibodies. In contrast, only 45 of the 407 non-colonized subjects had non-protective antitoxin titres. The prevalence of carriage increased with age among males as did the percentage of non-protected subjects. The prevalence of female carriers of corynebacteria was significantly lower. Serum samples from 12 subjects with different antibody titres to diphtheria toxoid reacted to varying degrees with whole-cell lysates of a number of species of corynebacteria. The results suggest that a causal relationship may exist between nasopharyngeal carriage of corynebacteria and a low anti-diphtheria toxin immune response.

  14. SubMICs of penicillin and erythromycin enhance biofilm formation and hydrophobicity of Corynebacterium diphtheriae strains.

    Science.gov (United States)

    Gomes, D L R; Peixoto, R S; Barbosa, E A B; Napoleão, F; Sabbadini, P S; dos Santos, K R N; Mattos-Guaraldi, A L; Hirata, R

    2013-05-01

    Subinhibitory concentrations (subMICs) of antibiotics may alter bacterial surface properties and change microbial physiology. This study aimed to investigate the effect of a subMIC (⅛ MIC) of penicillin (PEN) and erythromycin (ERY) on bacterial morphology, haemagglutinating activity, cell-surface hydrophobicity (CSH) and biofilm formation on glass and polystyrene surfaces, as well as the distribution of cell-surface acidic anionic residues of Corynebacterium diphtheriae strains (HC01 tox(-) strain; CDC-E8392 and 241 tox(+) strains). All micro-organisms tested were susceptible to PEN and ERY. Growth in the presence of PEN induced bacterial filamentation, whereas subMIC of ERY caused cell-size reduction of strains 241 and CDC-E8392. Adherence to human erythrocytes was reduced after growth in the presence of ERY, while CSH was increased by a subMIC of both antibiotics in bacterial adherence to n-hexadecane assays. Conversely, antibiotic inhibition of biofilm formation was not observed. All strains enhanced biofilm formation on glass after treatment with ERY, while only strain 241 increased glass adherence after cultivation in the presence of PEN. Biofilm production on polystyrene surfaces was improved by ⅛ MIC of ERY. After growth in the presence of both antimicrobial agents, strains 241 and CDC-E8392 exhibited anionic surface charges with focal distribution. In conclusion, subMICs of PEN and ERY modified bacterial surface properties and enhanced not only biofilm formation but also cell-surface hydrophobicity. Antibiotic-induced biofilm formation may contribute to the inconsistent success of antimicrobial therapy for C. diphtheriae infections.

  15. Study of Corynebacterium diphtheriae strains isolated in Romania, northwestern Russia and the Republic of Moldova.

    Science.gov (United States)

    Damian, Maria; Grimont, Francine; Narvskaya, Olga; Straut, Monica; Surdeanu, Maria; Cojocaru, Radu; Mokrousov, Igor; Diaconescu, Angela; Andronescu, Constantin; Melnic, Anatol; Mutoi, Ludmila; Grimont, Patrick A D

    2002-03-01

    A selection of 167 Corynebacterium diphtheriae strains isolated in Romania, the Russian Federation and the Republic of Moldova were analysed by biotyping, phage typing, the toxin production test and by molecular techniques such as ribotyping, pulsed field gel electrophoresis and random amplified polymorphic DNA, in order to establish the epidemiological relatedness, genetic divergence and strain circulation within and between the bordering countries. Using a set of five digoxigenin-labeled oligonucleotides and BstEII digestion, 34 ribotypes were identified. The strains isolated in the epidemic areas (Russia and Moldova) were very closely related but different from those isolated in Romania. C1 and C5 were the main ribotypes identified in these areas. Neither ribotype was found in Romania, where the main circulating types were C3 and C7. Field inversion gel electrophoresis was more discriminative than ribotyping and revealed 54 macrorestriction profiles after SfiI restriction. Both methods showed a significant homogeneity of the strains from epidemic areas and a large diversity among the Romanian strains. Random amplification was useful as an identification method for the epidemic strains, but not for the Romanian ones which displayed a large number of amplification profiles. The phenotypic methods associated with molecular typing techniques enabled distinguishing between strains, detecting the epidemic clone, and sustaining the absence of transmission across borders.

  16. Corynebacterium diphtheriae methionine sulfoxide reductase a exploits a unique mycothiol redox relay mechanism.

    Science.gov (United States)

    Tossounian, Maria-Armineh; Pedre, Brandán; Wahni, Khadija; Erdogan, Huriye; Vertommen, Didier; Van Molle, Inge; Messens, Joris

    2015-05-01

    Methionine sulfoxide reductases are conserved enzymes that reduce oxidized methionines in proteins and play a pivotal role in cellular redox signaling. We have unraveled the redox relay mechanisms of methionine sulfoxide reductase A of the pathogen Corynebacterium diphtheriae (Cd-MsrA) and shown that this enzyme is coupled to two independent redox relay pathways. Steady-state kinetics combined with mass spectrometry of Cd-MsrA mutants give a view of the essential cysteine residues for catalysis. Cd-MsrA combines a nucleophilic cysteine sulfenylation reaction with an intramolecular disulfide bond cascade linked to the thioredoxin pathway. Within this cascade, the oxidative equivalents are transferred to the surface of the protein while releasing the reduced substrate. Alternatively, MsrA catalyzes methionine sulfoxide reduction linked to the mycothiol/mycoredoxin-1 pathway. After the nucleophilic cysteine sulfenylation reaction, MsrA forms a mixed disulfide with mycothiol, which is transferred via a thiol disulfide relay mechanism to a second cysteine for reduction by mycoredoxin-1. With x-ray crystallography, we visualize two essential intermediates of the thioredoxin relay mechanism and a cacodylate molecule mimicking the substrate interactions in the active site. The interplay of both redox pathways in redox signaling regulation forms the basis for further research into the oxidative stress response of this pathogen.

  17. Opposite nucleotide usage biases in different parts of the Corynebacterium diphtheriae spaC gene.

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    Khrustalev, Vladislav Victorovich; Barkovsky, Eugene Victorovich; Kolodkina, Valentina Leonidovna; Khrustaleva, Tatyana Aleksandrovna

    2015-01-01

    In this work we described a bacterial open reading frame with two different directions of nucleotide usage biases in its two parts. The level of GC-content in third codon positions (3GC) is equal to 40.17 ± 0.22% during the most of the length of Corynebacterium diphtheriae spaC gene. However, in the 3'-end of the same gene (from codon #1600 to codon #1873) 3GC level is equal to 64.61 ± 0.91%. Using original methodology ('VVTAK Sliding window' and 'VVTAK VarInvar') we approved that there is an ongoing mutational AT-pressure during the most of the length of spaC gene (up to codon #1599), and there is an ongoing mutational G-pressure in the 3′-end of spaC. Intragenic promoters predicted by three different methods may be the cause of the differences in preferable types of nucleotide mutations in spaC parts because of their autonomous transcription.

  18. Carrier state of Haemophilus influenzae type b (Hib, Streptococcus pneumoniae, Streptococcus pyogenes, Neisseria meningitidis and Corynebacterium diphtheriae among school children in Pokhara, Nepal

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    Dharm Raj Bhatta

    2014-02-01

    Full Text Available Objective: To determine the incidence of carrier state of Haemophilus influenzae type b, Streptococcus pneumoniae (S. pneumoniae, Streptococcus pyogenes, Neisseria meningitidis and Corynebacterium diphtheriae among school children. Methods: Specimen from posterior pharyngeal wall and tonsils were collected on calcium alginate coated swabs from 1 02 participants. Processing of specimen and antimicrobial susceptibility testing was done by standard procedures. Results: Potential pathogens isolated in our study were S. pneumoniae (14.7%, Staphylococcus aureus (12.7%, Corynebacterium diphtheriae (3.9%, Streptococcus pyogenes (3.9% and Haemophilus influenzae (1.9%. Important findings in antibiogram include high resistance of S. pneumoniae to penicillin (73% and resistance of Staphylococcus aureus to oxacillin (23%. Conclusions: Pharyngeal colonization by S. pneumoniae among school children was found high and there is need of introduction of pneumococcal vaccines among children. Despite expected universal vaccination, pharyngeal colonization by Corynebacterium diphtheriae is possible and there is possibility of transmission.

  19. Culture-negative prosthetic valve endocarditis with concomitant septicemia due to a nontoxigenic Corynebacterium diphtheriae biotype gravis isolate in a patient with multiple risk factors.

    Science.gov (United States)

    Clinton, Lani Kai; Bankowski, Matthew J; Shimasaki, Teppei; Sae-Ow, Wichit; Whelen, A Christian; O'Connor, Norman; Kim, Wesley; Young, Royden

    2013-11-01

    A 54-year-old female with a prosthetic mitral valve presented with a 3-day history of dizziness, subjective fever, and chills. Blood cultures were positive for a pleomorphic Gram-positive rod. Initial phenotypic testing could only support the identification of a Corynebacterium species. Nucleic acid sequencing (16S rRNA) and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) were conclusive for Corynebacterium diphtheriae. Definitive phenotypic testing classified the strain as nontoxigenic C. diphtheriae biotype Gravis.

  20. Non-opsonic phagocytosis of homologous non-toxigenic and toxigenic Corynebacterium diphtheriae strains by human U-937 macrophages.

    Science.gov (United States)

    dos Santos, Cíntia Silva; dos Santos, Louisy Sanches; de Souza, Monica Cristina; dos Santos Dourado, Fernanda; de Souza de Oliveira Dias, Alexandre Alves; Sabbadini, Priscila Soares; Pereira, Gabriela Andrade; Cabral, Maulori Curié; Hirata Junior, Raphael; de Mattos-Guaraldi, Ana Luíza

    2010-01-01

    As interactions between bacteria and macrophages dictate the outcome of most infectious diseases, analyses of molecular mechanisms of non-opsonic phagocytosis should lead to new approaches for the prevention of diphtheria and systemic Corynebacterium diphtheriae infections. The present study aimed to evaluate human macrophage-bacteria interactions in the absence of opsonin antibodies and the influence of the tox gene on this process. Homologous C. diphtheriae tox+ and tox- strains were evaluated for adhesion, entering and survival within U-937 human macrophages at different incubation periods. Higher numbers of viable bacteria associated with and internalized by macrophages were demonstrated for the tox+ strain. However, viable intracellular bacteria were detected at T-24 hr only for the tox- strain. Cytoskeletal inhibitors, cytochalasin E, genistein and colchicine, inhibited intracellular viability of both strains at different levels. Bacterial replication was evidenced at T-24 hr in supernatants of monolayers infected with the tox- strain. Host cell death and nuclear alterations were evidenced by the Trypan blue exclusion assay and DAPI fluorescence microscopy. ELISA of histone-associated DNA fragments allowed detection of apoptosis and necrosis induced by tox+ and tox- strains at T-1 hr and T-3 hr. In conclusion, human macrophages in the absence of opsonins may not be promptly effective at killing diphtheria bacilli. The presence of the tox gene influences the susceptibility of C. diphtheriae to human macrophages and the outcome of non-opsonic phagocytosis. C. diphtheriae strains exhibit strategies to survive within macrophages and to exert apoptosis and necrosis in human phagocytic cells, independent of the tox gene.

  1. Diphtheria

    Science.gov (United States)

    Diphtheria is a serious bacterial infection. You can catch it from a person who has the infection ... as a toy, that has bacteria on it. Diphtheria usually affects the nose and throat. Symptoms include ...

  2. Expression and purification of the immunogenically active fragment B of the Park Williams 8 Corynebacterium diphtheriae strain toxin

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    D.V. Nascimento

    2010-05-01

    Full Text Available The construction of a hexahistidine-tagged version of the B fragment of diphtheria toxin (DTB represents an important step in the study of the biological properties of DTB because it will permit the production of pure recombinant DTB (rDTB in less time and with higher yields than currently available. In the present study, the genomic DNA of the Corynebacterium diphtheriae Park Williams 8 (PW8 vaccine strain was used as a template for PCR amplification of the dtb gene. After amplification, the dtb gene was cloned and expressed in competent Escherichia coli M15™ cells using the expression vector pQE-30™. The lysate obtained from transformed E. coli cells containing the rDTB PW8 was clarified by centrifugation and purified by affinity chromatography. The homogeneity of the purified rDTB PW8 was confirmed by immunoblotting using mouse polyclonal anti-diphtheria toxoid antibodies and the immune response induced in animals with rDTB PW8 was evaluated by ELISA and dermonecrotic neutralization assays. The main result of the present study was an alternative and accessible method for the expression and purification of immunogenically reactive rDTB PW8 using commercially available systems. Data also provided preliminary evidence that rabbits immunized with rDTB PW8 are able to mount a neutralizing response against the challenge with toxigenic C. diphtheriae.

  3. Heme Binding by Corynebacterium diphtheriae HmuT: Function and Heme Environment.

    Science.gov (United States)

    Draganova, Elizabeth B; Akbas, Neval; Adrian, Seth A; Lukat-Rodgers, Gudrun S; Collins, Daniel P; Dawson, John H; Allen, Courtni E; Schmitt, Michael P; Rodgers, Kenton R; Dixon, Dabney W

    2015-11-03

    The heme uptake pathway (hmu) of Corynebacterium diphtheriae utilizes multiple proteins to bind and transport heme into the cell. One of these proteins, HmuT, delivers heme to the ABC transporter HmuUV. In this study, the axial ligation of the heme in ferric HmuT is probed by examination of wild-type (WT) HmuT and a series of conserved heme pocket residue mutants, H136A, Y235A, and M292A. Characterization by UV-visible, resonance Raman, and magnetic circular dichroism spectroscopies indicates that H136 and Y235 are the axial ligands in ferric HmuT. Consistent with this assignment of axial ligands, ferric WT and H136A HmuT are difficult to reduce while Y235A is reduced readily in the presence of dithionite. The FeCO Raman shifts in WT, H136A, and Y235A HmuT-CO complexes provide further evidence of the axial ligand assignments. Additionally, these frequencies provide insight into the nonbonding environment of the heme pocket. Ferrous Y235A and the Y235A-CO complex reveal that the imidazole of H136 exists in two forms, one neutral and one with imidazolate character, consistent with a hydrogen bond acceptor on the H136 side of the heme. The ferric fluoride complex of Y235A reveals the presence of at least one hydrogen bond donor on the Y235 side of the heme. Hemoglobin utilization assays showed that the axial Y235 ligand is required for heme uptake in HmuT.

  4. Technetium-99m labeling and fibronectin binding ability of Corynebacterium diphtheriae; Marcacao de Corynebacterium diphtheriae com Tecnecio-99m e avaliacao da capacidade de ligacao a fibronectina de plasma humano

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    Souza, S.M.S.; Nagao, P.E.; Bernardo-Filho, M. [Universidade do Estado do Rio de Janeiro, RJ (Brazil). Inst. de Biologia Roberto Alcantara Gomes; Pereira, G.A.; Napoleao, F.; Andrade, A.F.B.; Hirata Junior, R.; Mattos-Guaraldi, A.L. [Universidade do Estado do Rio de Janeiro, RJ (Brazil). Faculdade de Ciencias Medicas

    2004-04-15

    The use of radionuclides has permitted advances in areas of clinical and scientific knowledge. Several molecules and cells have been labelled with Technetium-99m ({sup 99m}Tc). The stannous chloride (SnCl{sub 2}) has a significant influence on the labeling and stability of {sup 99m}Tc radiotracers. The frequent risk of diphtheria epidemics has intensified interest in the virulence factors of Corynebacterium diphtheriae. Although studies have looked at potential adhesins including haemagglutinins and exposed sugar residues, the molecular basis of mechanisms of adherence remains unclear. Adherence of pathogens to mammalian tissues may be mediated by fibronectin (FN) found in body fluids, matrix of connective tissues, and cell surfaces. In the present study we evaluated the binding ability to human plasma FN by {sup 99m}Tc labeled-C.diphtheriae. Due to adverse effects of stannous ions, microorganisms were submitted to survival and filamentation induction assays. Data showed a dose dependent susceptibility to SnCl{sub 2} bactericidal effects. Cell filamentation was observed for concentrations of SnCl{sub 2} > 110 {mu}g/ml. Adherence levels of {sup 99m}Tc labelled 241strain to coverslips coated with 20 {mu}g/ml FN were higher (P = 0.0037) than coated with bovine serum albumin. FN binding by the sucrose fermenting 241 C. diphtheriae strain (8.9% + 2.6) was significantly lower (P=0.0139) than Staphylococcus aureus Cowan I strain (34.1% {+-} 1.2). Therefore, bacterial {sup 99m}Tc labeling represents an additional tool that may contribute to the comprehension of C. diphtheriae interactions with host receptors such as FN that act as biological organizers by holding bacterial cells in position and guiding their migration. (author)

  5. Sexually transmitted diphtheria.

    Science.gov (United States)

    Berger, Anja; Lensing, Carmen; Konrad, Regina; Huber, Ingrid; Hogardt, Michael; Sing, Andreas

    2013-03-01

    Diphtheria is caused by diphtheria toxin-producing Corynebacterium species. While classical respiratory diphtheria is transmitted by droplets, cutaneous diphtheria often results from minor trauma. This report concerns the first case of sexually transmitted diphtheria in a patient with non-gonococcal urethritis after orogenital contact.

  6. Corynebacterium diphtheriae as an emerging pathogen in nephrostomy catheter-related infection: evaluation of traits associated with bacterial virulence.

    Science.gov (United States)

    Gomes, Débora L R; Martins, Carlos A S; Faria, Lúcia M D; Santos, Louisy S; Santos, Cintia S; Sabbadini, Priscila S; Souza, Mônica C; Alves, Gabriela B; Rosa, Ana C P; Nagao, Prescilla E; Pereira, Gabriela A; Hirata, Raphael; Mattos-Guaraldi, Ana L

    2009-11-01

    Corynebacterium diphtheriae still represents a global medical challenge, particularly due to the significant number of individuals susceptible to diphtheria and the emergence of non-toxigenic strains as the causative agents of invasive infections. In this study, we characterized the clinical and microbiological features of what we believe to be the first case of C. diphtheriae infection of a percutaneous nephrostomy catheter insertion site in an elderly patient with a fatal bladder cancer. Moreover, we demonstrated the potential role of adherence, biofilm formation and fibrin deposition traits in C. diphtheriae from the catheter-related infection. Non-toxigenic C. diphtheriae isolated from the purulent discharge (named strain BR-CAT5003748) was identified by the API Coryne system (code 1 010 324) and a multiplex PCR for detection of dtxR and tox genes. Strain BR-CAT5003748 showed resistance to oxacillin, ceftazidime and ciprofloxacin. In experiments performed in vitro, the catheter isolate was classified as moderately hydrophobic and as moderately adherent to polystyrene surfaces. Glass provided a more effective surface for biofilm formation than polystyrene. Micro-organisms adhered to (>1.5 x 10(6) c.f.u.) and multiplied on surfaces of polyurethane catheters. Microcolony formation (a hallmark of biofilm formation) and amorphous accretions were observed by scanning electron microscopy on both external and luminal catheter surfaces. Micro-organisms yielded simultaneous expression of localized adherence-like and aggregative-like (LAL/AAL) adherence patterns to HEp-2 cells. Interestingly, the coagulase tube test resulted in the formation of a thin layer of fibrin embedded in rabbit plasma by the non-toxigenic BR-CAT5003748 strain. In conclusion, C. diphtheriae should be recognized as a potential cause of catheter-related infections in at-risk populations such as elderly and cancer patients. LAL/AAL strains may be associated with virulence traits that enable C

  7. Exploration on relative quality standard of Corynebacterium diphtheriae culture medium%白喉杆菌培养基相关质控标准探讨

    Institute of Scientific and Technical Information of China (English)

    邓雪莲; 李应伟; 唐朝晖

    2013-01-01

    Objective To establish relative quality standards of Corynebacterium diphtheriae culture medium.Methods Corynebacterium diphtheriae culture media with ≥ 1.8 g/L and < 1.8 g/L ammonia nitrogen were prepared respectively to use for Corynebacterium diphtheriae culture in large fermtor.The statistical analysis of the culture results were made by t test,and the optimal culture medium was identified.Fifteen batches of Corynebacterium diphtheriae culture media were prepared according to the identified formula and used to large fermentor culture.Quantities of diphtheria toxin harvested by culture were detected,and correlativity between ammonia nitrogen contents in Corynebacterium diphtheriae culture medium and diphtheria toxin produced by Corynebacterium diphtheriae was analysed.Fifteen batches of 15%-20% maltose solutions were made up and fed into large fermentor as supplement during Corynebacterium diphtheriae culture.Quantities of diphtheria toxin harvested by culture were detected,and correlativity between concentrations of maltose solutions and diphtheria toxin produced by Corynebacterium diphtheriae was analysed.Results Quantities of diphtheria toxin harvested from Corynebacterium diphtheriae culture media with ≥ 1.8 g/L ammonia nitrogen were significantly higher than those harvested from Corynebacterium diphtheriae culture media with < 1.8 g/L ammonia nitrogen(t =0.5635,P < 0.05).Positive linear correlation (r =0.52) was showed between ammonia nitrogen contents in Corynebacterium diphtheriae culture medium and quantities of diphtheria toxin in ranges of identified ammonia nitrogen contents (1.8-2.0 g/L).When concentrations of maltose solutions ranged from 15% to 20%,negative linear correlation (r =-0.53) was showed between concentrations of maltose solutions and quantities of diphtheria toxin.Conclusion When ammonia nitrogen contents in Corynebacterium diphtheriae culture medium and concentrations of maltose solutions for feeding into large

  8. Pilus gene pool variation and the virulence of Corynebacterium diphtheriae clinical isolates during infection of a nematode.

    Science.gov (United States)

    Broadway, Melissa M; Rogers, Elizabeth A; Chang, Chungyu; Huang, I-Hsiu; Dwivedi, Prabhat; Yildirim, Suleyman; Schmitt, Michael P; Das, Asis; Ton-That, Hung

    2013-08-01

    Toxigenic Corynebacterium diphtheriae strains cause diphtheria in humans. The toxigenic C. diphtheriae isolate NCTC13129 produces three distinct heterotrimeric pili that contain SpaA, SpaD, and SpaH, making up the shaft structure. The SpaA pili are known to mediate bacterial adherence to pharyngeal epithelial cells. However, to date little is known about the expression of different pili in various clinical isolates and their importance in bacterial pathogenesis. Here, we characterized a large collection of C. diphtheriae clinical isolates for their pilin gene pool by PCR and for the expression of the respective pilins by immunoblotting with antibodies against Spa pilins. Consistent with the role of a virulence factor, the SpaA-type pili were found to be prevalent among the isolates, and most significantly, corynebacterial adherence to pharyngeal epithelial cells was strictly correlated with isolates that were positive for the SpaA pili. By comparison, the isolates were heterogeneous for the presence of SpaD- and SpaH-type pili. Importantly, using Caenorhabditis elegans as a model host for infection, we show here that strain NCTC13129 rapidly killed the nematodes, the phenotype similar to isolates that were positive for toxin and all pilus types. In contrast, isogenic mutants of NCTC13129 lacking SpaA-type pili or devoid of toxin and SpaA pili exhibited delayed killing of nematodes with similar kinetics. Consistently, nontoxigenic or toxigenic isolates that lack one, two, or all three pilus types were also attenuated in virulence. This work signifies the important role of pili in corynebacterial pathogenesis and provides a simple host model to identify additional virulence factors.

  9. Matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF) mass spectrometry as a tool for rapid diagnosis of potentially toxigenic Corynebacterium species in the laboratory management of diphtheria-associated bacteria.

    Science.gov (United States)

    Konrad, R; Berger, A; Huber, I; Boschert, V; Hörmansdorfer, S; Busch, U; Hogardt, M; Schubert, S; Sing, A

    2010-10-28

    The rapid identification of the potentially toxigenic Corynebacterium species, C. diphtheriae, C. ulcerans and C. pseudotuberculosis is essential for diagnosis and treatment of diphtheria and diphtheria-like diseases. We used matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDIT-OF MS) in comparison with classical microbiological and molecular methods on 116 Corynebacterium strains. All 90 potentially toxigenic Corynebacterium strains collected by the German National Consiliary Laboratory on Diphtheria in a period of more than ten years were correctly identified by MALDI-TOF MS. We propose an algorithm for fast and reliable diagnosis of diphtheria incorporating MALDI-TOF MS, real-time tox PCR and Elek testing.

  10. Structure of the response regulator ChrA in the haem-sensing two-component system of Corynebacterium diphtheriae.

    Science.gov (United States)

    Doi, Akihiro; Nakamura, Hiro; Shiro, Yoshitsugu; Sugimoto, Hiroshi

    2015-08-01

    ChrA is a response regulator (RR) in the two-component system involved in regulating the degradation and transport of haem (Fe-porphyrin) in the pathogen Corynebacterium diphtheriae. Here, the crystal structure of full-length ChrA is described at a resolution of 1.8 Å. ChrA consists of an N-terminal regulatory domain, a long linker region and a C-terminal DNA-binding domain. A structural comparison of ChrA with other RRs revealed substantial differences in the relative orientation of the two domains and the conformation of the linker region. The structural flexibility of the linker could be an important feature in rearrangement of the domain orientation to create a dimerization interface to bind DNA during haem-sensing signal transduction.

  11. Emergence and molecular characterisation of non-toxigenic tox gene-bearing Corynebacterium diphtheriae biovar mitis in the United Kingdom, 2003-2012.

    Science.gov (United States)

    Zakikhany, K; Neal, S; Efstratiou, A

    2014-06-05

    Non-toxigenic Corynebacterium diphtheriae have become increasingly recognised as emerging pathogens across Europe causing severe invasive disease. A subset of non-toxigenic C. diphtheriae are ‘non-toxigenic tox gene-bearing’ (NTTB) strains; these strains are genotypically toxpositive, but do not express the protein. The circulation of NTTB strains was first observed during the 1990s upsurge of diphtheria in Eastern Europe but has not been reported in other European countries. Circulation of NTTB strains could be considered an increased risk for diphtheria and other related diseases, given their possible role as a tox gene reservoir with the theoretical risk of re-emerging toxin expression. Here we report the characterisation of 108 non-toxigenic C. diphtheriae biovar mitis isolates submitted to the World Health Organization (WHO) Global Reference Centre for Diphtheria at Public Health England, London, between 2003 and 2012, in order to determine the presence of NTTB strains. Using molecular methods, five NTTB isolates were identified; four human isolates (MLST type 212) and one isolate from a companion cat (MLST type 40). The emergence of these strains could indicate continuation of the circulation of potentially toxigenic strains and appropriate laboratory diagnostic methods should be used for detection. Given the complacency that currently exists in Europe awareness with regards to diphtheria diagnostics must be enhanced.

  12. Identification of a DtxR-regulated operon that is essential for siderophore-dependent iron uptake in Corynebacterium diphtheriae.

    Science.gov (United States)

    Qian, Yilei; Lee, John H; Holmes, Randall K

    2002-09-01

    The diphtheria toxin repressor (DtxR) uses Fe(2+) as a corepressor and inhibits transcription from iron-regulated promoters (IRPs) in Corynebacterium diphtheriae. A new IRP, designated IRP6, was cloned from C. diphtheriae by a SELEX-like procedure. DtxR bound to IRP6 in vitro only in the presence of appropriate divalent metal ions, and repression of IRP6 by DtxR in an Escherichia coli system was iron dependent. The open reading frames (ORFs) downstream from IRP6 and previously described promoter IRP1 were found to encode proteins homologous to components of ATP-binding cassette (ABC) transport systems involved in high-affinity iron uptake in other bacteria. IRP1 and IRP6 were repressed under high-iron conditions in wild-type C. diphtheriae C7(beta), but they were expressed constitutively in C7(beta) mutant strains HC1, HC3, HC4, and HC5, which were shown previously to be defective in corynebactin-dependent iron uptake. A clone of the wild-type irp6 operon (pCM6ABC) complemented the constitutive corynebactin production phenotype of HC1, HC4, and HC5 but not of HC3, whereas a clone of the wild-type irp1 operon failed to complement any of these strains. Complementation by subclones of pCM6ABC demonstrated that mutant alleles of irp6A, irp6C, and irp6B were responsible for the phenotypes of HC1, HC4, and HC5, respectively. The irp6A allele in HC1 and the irp6B allele in HC5 encoded single amino acid substitutions in their predicted protein products, and the irp6C allele in HC4 caused premature chain termination of its predicted protein product. Strain HC3 was found to have a chain-terminating mutation in dtxR in addition to a missense mutation in its irp6B allele. These findings demonstrated that the irp6 operon in C. diphtheriae encodes a putative ABC transporter, that specific mutant alleles of irp6A, irp6B, and irp6C are associated with defects in corynebactin-dependent iron uptake, and that complementation of these mutant alleles restores repression of corynebactin

  13. Cell surface display of minor pilin adhesins in the form of a simple heterodimeric assembly in Corynebacterium diphtheriae.

    Science.gov (United States)

    Chang, Chungyu; Mandlik, Anjali; Das, Asis; Ton-That, Hung

    2011-03-01

    Pilus assembly in Gram-positive bacteria occurs by a two-step mechanism, whereby pilins are polymerized and then covalently anchored to the cell wall. In Corynebacterium diphtheriae, the pilin-specific sortase SrtA catalyses polymerization of the SpaA-type pilus, consisting of the shaft pilin SpaA, tip pilin SpaC and minor pilin SpaB. Cell wall anchoring of the SpaA polymers is triggered when SrtA incorporates SpaB into the pilus base via lysine-mediated transpeptidation; anchoring to the cell wall peptidoglycan is subsequently catalysed by the housekeeping sortase SrtF. Here we show that SpaB and SpaC formed a heterodimer independent of SpaA polymerization. SrtA was absolutely required for the formation of the SpaBC heterodimer, while SrtF facilitated the optimal cell wall anchoring of this heterodimer. Alanine substitution of the SpaB lysine residue K139 or truncation of the SpaB cell wall-sorting signal (CWSS) abolished assembly of the SpaBC heterodimer, hence underscoring SpaB function in transpeptidation and cell wall linkage. Importantly, sortase specificity for the cell wall-anchoring step was found to be dependent on the LAFTG motif within the SpaB CWSS. Thus, C. diphtheriae employs a common sortase-catalysed mechanism involving lysine-mediated transpeptidation to generate both adhesive pilus and simple heterodimeric structures on the bacterial the cell wall.

  14. Comparison of four molecular typing methods for characterization of Corynebacterium diphtheriae and determination of transcontinental spread of C. diphtheriae based on BstEII rRNA gene profiles.

    Science.gov (United States)

    De Zoysa, Aruni; Hawkey, Peter; Charlett, Andre; Efstratiou, Androulla

    2008-11-01

    The diphtheria epidemic in the Russian Federation in the 1990s made diphtheria a focus of global concern once again. The development of rapid and reproducible typing methods for the molecular characterization of Corynebacterium diphtheriae has become a priority in order to be able to monitor the spread of this important pathogen on a global scale. We report on a comparison of four molecular typing methods (ribotyping, pulsed-field gel electrophoresis [PFGE], random amplification of polymorphic DNA [RAPD], and amplified fragment length polymorphism [AFLP]) for the characterization of C. diphtheriae strains. Initially, 755 isolates originating from 26 countries were analyzed by ribotyping. One strain of each ribotype was then randomly chosen and characterized by PFGE, RAPD, and AFLP. In order to ascertain whether the Eastern European epidemic ribotype could be further discriminated, 10 strains of ribotype D1 (the epidemic ribotype) from different geographical regions were randomly chosen and subjected to analysis by PFGE, RAPD, and AFLP. The results revealed that ribotyping is highly discriminatory and reproducible and is currently the method of choice for typing C. diphtheriae. PFGE and AFLP were less discriminatory than ribotyping and RAPD. An assessment of the transcontinental spread of the organism showed that several genotypes of C. diphtheriae circulated on different continents of the world and that each outbreak was caused by a distinct clone. The ribotypes seen in Europe appeared to be distinct from those seen elsewhere, and certain ribotypes appeared to be unique to particular countries.

  15. Estudo da difteria na cidade do Recife. I. Nota sôbre levantamento de portadores de Corynebacterium diphtheriae no bairro dos Coelhos Survey on diphtheriae carriers in "Bairro dos Coelhos" Recife, Brazil

    Directory of Open Access Journals (Sweden)

    Dalva A. Mello

    1969-06-01

    Full Text Available De uma amostra probabilística do bairro dos Coelhos da cidade do Recife, 410 indivíduos foram examinados para verificação de portadores de difteria. Sòmente duas amostras de C. diphtheriae foram isoladas de duas crianças de 8 a 9 anos, as quais não apresentaram sintomatologia compatível com o quadro diftérico.From a limited population living around the University Hospital in Recife, Brazil a randomic sample was examined in order to identify diphtheria carriers. Swabs were made from 410 persons in a house-to-house survey. Two strains of Corynebacterium diphtheriae were isolated from healthy 8 and 9-year old children.

  16. Report: seroprevalence of corynebacterium diphtheriae among vaccinated population of Rawalpindi/Islamabad, Pakistan.

    Science.gov (United States)

    Faryal, Rani; Noreen, Zobia; Tahir, Faheem; Rehman, Zahidur

    2013-05-01

    Diphtheria is a communicable disease of global significance, and its outbreaks have to be reported to the world community under the International Health Regulations (IHR). A pilot seroepidemiological survey was conducted to assess immunity status of diphtheria among healthy individuals of Rawalpindi/Islamabad (Pakistan), who had been administered at least one dose of the vaccine against the disease, as part of childhood vaccination. The study group comprised of 128 healthy subjects, grouped according to the decade representing their age. Antidiphtheria IgG levels were measured by Enzyme Linked Immunosorbent Assay (ELISA) method. The studied sample showed 100% prevalence of diphtheria antitoxin, confirming prior vaccination; however 49.2% exhibited only minimal protection against diphtheria. Full protection was observed in a significantly higher (p=0.013) percentage of males (54.45%) as compared to female subjects (33.33%). Maximum level of serum antibodies were seen in 1-10 year age group (0.195+0.031 IU/mL), which was significantly higher than that recorded in the age group of 11-20 (p=0.024) and above 30 years (p=0.0064). The present results emphasize the need for periodical booster immunization in adolescents and adults, after primary childhood immunization.

  17. [The use of MLVA for Corynebacterium diphtheriae genotyping--preliminary studies].

    Science.gov (United States)

    Zasada, Aleksandra A; Jagielski, Marek; Rzeczkowska, Magdalena; Januszkiewicz, Aleksandra

    2011-01-01

    The complete genome sequence of strain NCTC 13129 C. diphtheriae were investigated in order to identify tandem repeats (VNTR). From 75 VNTR loci identified in the genome 14 were selected. Primers were designed and PCR conditions were optimized for amplification of the selected VNTR markers. Preliminary studies of usefulness of selected VNTR markers were conducted using a group of 28 C. diphtheriae strains. From 14 markers 8 were regarded as potentially useful. The diversity of individual markers ranged from 1 to 6 alleles (Simpson index from 0 to 0,746). No diversity were observed for 3 VNTR markers but it could be a results of too small group of strains analyzed in the tests. Simpson diversity index calculated for all the markers tested on 28 strains was 0,87. Results of the preliminary studies showed usefulness of MLVA for C. diphtheriae genotyping. Nevertheless, confirmation of reliability of the method should be done using a large group of strains. Moreover, the method should be compared with other genotyping methods.

  18. Corynebacterium diphtheriae putative tellurite-resistance protein (CDCE8392_0813 contributes to the intracellular survival in human epithelial cells and lethality of Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Louisy Sanches dos Santos

    2015-01-01

    Full Text Available Corynebacterium diphtheriae, the aetiologic agent of diphtheria, also represents a global medical challenge because of the existence of invasive strains as causative agents of systemic infections. Although tellurite (TeO32- is toxic to most microorganisms, TeO32--resistant bacteria, including C. diphtheriae, exist in nature. The presence of TeO32--resistance (TeR determinants in pathogenic bacteria might provide selective advantages in the natural environment. In the present study, we investigated the role of the putative TeR determinant (CDCE8392_813 gene in the virulence attributes of diphtheria bacilli. The disruption of CDCE8392_0813 gene expression in the LDCIC-L1 mutant increased susceptibility to TeO32- and reactive oxygen species (hydrogen peroxide, but not to other antimicrobial agents. The LDCIC-L1 mutant also showed a decrease in both the lethality of Caenorhabditis elegans and the survival inside of human epithelial cells compared to wild-type strain. Conversely, the haemagglutinating activity and adherence to and formation of biofilms on different abiotic surfaces were not regulated through the CDCE8392_0813 gene. In conclusion, the CDCE8392_813 gene contributes to the TeR and pathogenic potential of C. diphtheriae.

  19. Corynebacterium diphtheriae putative tellurite-resistance protein (CDCE8392_0813) contributes to the intracellular survival in human epithelial cells and lethality of Caenorhabditis elegans.

    Science.gov (United States)

    Santos, Louisy Sanches Dos; Antunes, Camila Azevedo; Santos, Cintia Silva Dos; Pereira, José Augusto Adler; Sabbadini, Priscila Soares; Luna, Maria das Graças de; Azevedo, Vasco; Hirata Júnior, Raphael; Burkovski, Andreas; Asad, Lídia Maria Buarque de Oliveira; Mattos-Guaraldi, Ana Luíza

    2015-08-01

    Corynebacterium diphtheriae, the aetiologic agent of diphtheria, also represents a global medical challenge because of the existence of invasive strains as causative agents of systemic infections. Although tellurite (TeO32-) is toxic to most microorganisms, TeO32--resistant bacteria, including C. diphtheriae, exist in nature. The presence of TeO32--resistance (TeR) determinants in pathogenic bacteria might provide selective advantages in the natural environment. In the present study, we investigated the role of the putative TeR determinant (CDCE8392_813gene) in the virulence attributes of diphtheria bacilli. The disruption of CDCE8392_0813 gene expression in the LDCIC-L1 mutant increased susceptibility to TeO32- and reactive oxygen species (hydrogen peroxide), but not to other antimicrobial agents. The LDCIC-L1 mutant also showed a decrease in both the lethality of Caenorhabditis elegans and the survival inside of human epithelial cells compared to wild-type strain. Conversely, the haemagglutinating activity and adherence to and formation of biofilms on different abiotic surfaces were not regulated through the CDCE8392_0813 gene. In conclusion, the CDCE8392_813 gene contributes to the TeR and pathogenic potential of C. diphtheriae.

  20. Corynebacterium diphtheriae putative tellurite-resistance protein (CDCE8392_0813 contributes to the intracellular survival in human epithelial cells and lethality of Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Louisy Sanches dos Santos

    2015-08-01

    Full Text Available Corynebacterium diphtheriae, the aetiologic agent of diphtheria, also represents a global medical challenge because of the existence of invasive strains as causative agents of systemic infections. Although tellurite (TeO32- is toxic to most microorganisms, TeO32--resistant bacteria, including C. diphtheriae, exist in nature. The presence of TeO32--resistance (TeR determinants in pathogenic bacteria might provide selective advantages in the natural environment. In the present study, we investigated the role of the putative TeR determinant (CDCE8392_813gene in the virulence attributes of diphtheria bacilli. The disruption of CDCE8392_0813 gene expression in the LDCIC-L1 mutant increased susceptibility to TeO32- and reactive oxygen species (hydrogen peroxide, but not to other antimicrobial agents. The LDCIC-L1 mutant also showed a decrease in both the lethality of Caenorhabditis elegansand the survival inside of human epithelial cells compared to wild-type strain. Conversely, the haemagglutinating activity and adherence to and formation of biofilms on different abiotic surfaces were not regulated through the CDCE8392_0813 gene. In conclusion, the CDCE8392_813 gene contributes to the TeR and pathogenic potential of C. diphtheriae.

  1. HtaA is an iron-regulated hemin binding protein involved in the utilization of heme iron in Corynebacterium diphtheriae.

    Science.gov (United States)

    Allen, Courtni E; Schmitt, Michael P

    2009-04-01

    Many human pathogens, including Corynebacterium diphtheriae, the causative agent of diphtheria, use host compounds such as heme and hemoglobin as essential iron sources. In this study, we examined the Corynebacterium hmu hemin transport region, a genetic cluster that contains the hmuTUV genes encoding a previously described ABC-type hemin transporter and three additional genes, which we have designated htaA, htaB, and htaC. The hmu gene cluster is composed of three distinct transcriptional units. The htaA gene appears to be part of an iron- and DtxR-regulated operon that includes hmuTUV, while htaB and htaC are transcribed from unique DtxR-regulated promoters. Nonpolar deletion of either htaA or the hmuTUV genes resulted in a reduced ability to use hemin as an iron source, while deletion of htaB had no effect on hemin iron utilization in C. diphtheriae. A comparison of the predicted amino acid sequences of HtaA and HtaB showed that they share some sequence similarity, and both proteins contain leader sequences and putative C-terminal transmembrane regions. Protein localization studies with C. diphtheriae showed that HtaA is associated predominantly with the cell envelope when the organism is grown in minimal medium but is secreted during growth in nutrient-rich broth. HtaB and HmuT were detected primarily in the cytoplasmic membrane fraction regardless of the growth medium. Hemin binding studies demonstrated that HtaA and HtaB are able to bind hemin, suggesting that these proteins may function as cell surface hemin receptors in C. diphtheriae.

  2. Outbreak investigation for toxigenic Corynebacterium diphtheriae wound infections in refugees from Northeast Africa and Syria in Switzerland and Germany by whole genome sequencing.

    Science.gov (United States)

    Meinel, D M; Kuehl, R; Zbinden, R; Boskova, V; Garzoni, C; Fadini, D; Dolina, M; Blümel, B; Weibel, T; Tschudin-Sutter, S; Widmer, A F; Bielicki, J A; Dierig, A; Heininger, U; Konrad, R; Berger, A; Hinic, V; Goldenberger, D; Blaich, A; Stadler, T; Battegay, M; Sing, A; Egli, A

    2016-12-01

    Toxigenic Corynebacterium diphtheriae is an important and potentially fatal threat to patients and public health. During the current dramatic influx of refugees into Europe, our objective was to use whole genome sequencing for the characterization of a suspected outbreak of C. diphtheriae wound infections among refugees. After conventional culture, we identified C. diphtheriae using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) and investigated toxigenicity by PCR. Whole genome sequencing was performed on a MiSeq Illumina with >70×coverage, 2×250 bp read length, and mapping against a reference genome. Twenty cases of cutaneous C. diphtheriae in refugees from East African countries and Syria identified between April and August 2015 were included. Patients presented with wound infections shortly after arrival in Switzerland and Germany. Toxin production was detected in 9/20 (45%) isolates. Whole genome sequencing-based typing revealed relatedness between isolates using neighbour-joining algorithms. We detected three separate clusters among epidemiologically related refugees. Although the isolates within a cluster showed strong relatedness, isolates differed by >50 nucleotide polymorphisms. Toxigenic C. diphtheriae associated wound infections are currently observed more frequently in Europe, due to refugees travelling under poor hygienic conditions. Close genetic relatedness of C. diphtheriae isolates from 20 refugees with wound infections indicates likely transmission between patients. However, the diversity within each cluster and phylogenetic time-tree analysis suggest that transmissions happened several months ago, most likely outside Europe. Whole genome sequencing offers the potential to describe outbreaks at very high resolution and is a helpful tool in infection tracking and identification of transmission routes.

  3. Utilization of host iron sources by Corynebacterium diphtheriae: multiple hemoglobin-binding proteins are essential for the use of iron from the hemoglobin-haptoglobin complex.

    Science.gov (United States)

    Allen, Courtni E; Schmitt, Michael P

    2015-02-01

    The use of hemin iron by Corynebacterium diphtheriae requires the DtxR- and iron-regulated ABC hemin transporter HmuTUV and the secreted Hb-binding protein HtaA. We recently described two surface anchored proteins, ChtA and ChtC, which also bind hemin and Hb. ChtA and ChtC share structural similarities to HtaA; however, a function for ChtA and ChtC was not determined. In this study, we identified additional host iron sources that are utilized by C. diphtheriae. We show that several C. diphtheriae strains use the hemoglobin-haptoglobin (Hb-Hp) complex as an iron source. We report that an htaA deletion mutant of C. diphtheriae strain 1737 is unable to use the Hb-Hp complex as an iron source, and we further demonstrate that a chtA-chtC double mutant is also unable to use Hb-Hp iron. Single-deletion mutants of chtA or chtC use Hb-Hp iron in a manner similar to that of the wild type. These findings suggest that both HtaA and either ChtA or ChtC are essential for the use of Hb-Hp iron. Enzyme-linked immunosorbent assay (ELISA) studies show that HtaA binds the Hb-Hp complex, and the substitution of a conserved tyrosine (Y361) for alanine in HtaA results in significantly reduced binding. C. diphtheriae was also able to use human serum albumin (HSA) and myoglobin (Mb) but not hemopexin as iron sources. These studies identify a biological function for the ChtA and ChtC proteins and demonstrate that the use of the Hb-Hp complex as an iron source by C. diphtheriae requires multiple iron-regulated surface components.

  4. Genetic relationships of Corynebacterium diphtheriae strains isolated from a diphtheria case and carriers by restriction fragment length polymorphism of rRNA genes Relação genética de cepas de Corynebacterium diphtheriae isoladas de caso e seus contatos por RLFP de rRNA gene

    Directory of Open Access Journals (Sweden)

    Claudio Tavares Sacchi

    1995-08-01

    Full Text Available In the present study we report the results of an analysis, based on ribotyping of Corynebacterium diphtheriae intermedius strains isolated from a 9 years old child with clinical diphtheria and his 5 contacts. Quantitative analysis of RFLPs of rRNA was used to determine relatedness of these 7 C.diphtheriae strains providing support data in the diphtheria epidemiology. We have also tested those strains for toxigenicity in vitro by using the Elek's gel diffusion method and in vivo by using cell culture method on cultured monkey kidney cell (VERO cells. The hybridization results revealed that the 5 C.diphtheriae strains isolated from contacts and one isolated from the clinical case (nose case strain had identical RFLP patterns with all 4 restriction endonucleases used, ribotype B. The genetic distance from this ribotype and ribotype A (throat case strain, that we initially assumed to be responsible for the illness of the patient, was of 0.450 showing poor genetic correlation among these two ribotypes. We found no significant differences concerned to the toxin production by using the cell culture method. In conclusion, the use of RFLPs of rRNA gene was successful in detecting minor differences in closely related toxigenic C.diphtheriae intermedius strains and providing information about genetic relationships among them.No presente estudo, nós reportamos os resultados de uma análise, baseada na ribotipagem de cepas de C. diphtheriae intermedius isoladas de uma criança de 9 anos com difteria e seus 5 contatos. Análise quantitativa por RFLP de rRNA foi usada para determinar a relação destas 7 cepas de C. diphtheriae fornecendo dados de interesse epidemiológico. Nós também testamos estas cepas para toxicidade in vitro usando método de difusão de Elek e in vivo usando método de cultura celular com células VERO. Os resultados de hibridização revelaram que as 5 cepas de C. diphtheriae isoladas dos contatos e uma isolada do caso (cepa isolada

  5. Corynebacterium diphtheriae 67-72p hemagglutinin, characterized as the protein DIP0733, contributes to invasion and induction of apoptosis in HEp-2 cells.

    Science.gov (United States)

    Sabbadini, Priscila Soares; Assis, Maria Cristina; Trost, Eva; Gomes, Débora Leandro Rama; Moreira, Lilian Oliveira; Dos Santos, Cíntia Silva; Pereira, Gabriela Andrade; Nagao, Prescilla Emy; Azevedo, Vasco Ariston de Carvalho; Hirata Júnior, Raphael; Dos Santos, André Luis Souza; Tauch, Andreas; Mattos-Guaraldi, Ana Luíza

    2012-03-01

    Although Corynebacterium diphtheriae has been classically described as an exclusively extracellular pathogen, there is growing evidence that it may be internalized by epithelial cells. The aim of the present report was to investigate the nature and involvement of the surface-exposed non-fimbrial 67-72 kDa proteins (67-72p), previously characterized as adhesin/hemagglutinin, in C. diphtheriae internalization by HEp-2 cells. Transmission electron microscopy and bacterial internalization inhibition assays indicated the role of 67-72p as invasin for strains of varied sources. Cytoskeletal changes with accumulation of polymerized actin in HEp-2 cells beneath adherent 67-72p-adsorbed microspheres were observed by the Fluorescent actin staining test. Trypan blue staining method and Methylthiazole tetrazolium reduction assay showed a significant decrease in viability of HEp-2 cells treated with 67-72p. Morphological changes in HEp-2 cells observed after treatment with 67-72p included vacuolization, nuclear fragmentation and the formation of apoptotic bodies. Flow cytometry revealed an apoptotic volume decrease in HEp-2 cells treated with 67-72p. Moreover, a double-staining assay using Propidium Iodide/Annexin V gave information about the numbers of vital vs. early apoptotic cells and late apoptotic or secondary necrotic cells. The comparative analysis of MALDI-TOF MS experiments with the probes provided for 67-72p CDC-E8392 with an in silico proteome deduced from the complete genome sequence of C. diphtheriae identified with significant scores 67-72p as the protein DIP0733. In conclusion, DIP0733 (67-72p) may be directly implicated in bacterial invasion and apoptosis of epithelial cells in the early stages of diphtheria and C. diphtheriae invasive infection.

  6. A thiol-disulfide oxidoreductase of the Gram-positive pathogen Corynebacterium diphtheriae is essential for viability, pilus assembly, toxin production and virulence.

    Science.gov (United States)

    Reardon-Robinson, Melissa E; Osipiuk, Jerzy; Jooya, Neda; Chang, Chungyu; Joachimiak, Andrzej; Das, Asis; Ton-That, Hung

    2015-12-01

    The Gram-positive pathogen Corynebacterium diphtheriae exports through the Sec apparatus many extracellular proteins that include the key virulence factors diphtheria toxin and the adhesive pili. How these proteins attain their native conformations after translocation as unfolded precursors remains elusive. The fact that the majority of these exported proteins contain multiple cysteine residues and that several membrane-bound oxidoreductases are encoded in the corynebacterial genome suggests the existence of an oxidative protein-folding pathway in this organism. Here we show that the shaft pilin SpaA harbors a disulfide bond in vivo and alanine substitution of these cysteines abrogates SpaA polymerization and leads to the secretion of degraded SpaA peptides. We then identified a thiol-disulfide oxidoreductase (MdbA), whose structure exhibits a conserved thioredoxin-like domain with a CPHC active site. Remarkably, deletion of mdbA results in a severe temperature-sensitive cell division phenotype. This mutant also fails to assemble pilus structures and is greatly defective in toxin production. Consistent with these defects, the ΔmdbA mutant is attenuated in a guinea pig model of diphtheritic toxemia. Given its diverse cellular functions in cell division, pilus assembly and toxin production, we propose that MdbA is a component of the general oxidative folding machine in C. diphtheriae.

  7. A slow-forming isopeptide bond in the structure of the major pilin SpaD from Corynebacterium diphtheriae has implications for pilus assembly

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Hae Joo; Paterson, Neil G. [University of Auckland, Private Bag 92019, Auckland 1142 (New Zealand); Kim, Chae Un [Cornell University, Ithaca, NY 14853 (United States); Middleditch, Martin [University of Auckland, Private Bag 92019, Auckland 1142 (New Zealand); Chang, Chungyu; Ton-That, Hung [University of Texas–Houston Medical School, Houston, TX 77030 (United States); Baker, Edward N., E-mail: ted.baker@auckland.ac.nz [University of Auckland, Private Bag 92019, Auckland 1142 (New Zealand)

    2014-05-01

    Two crystal structures of the major pilin SpaD from C. diphtheriae have been determined at 1.87 and 2.5 Å resolution. The N-terminal domain is found to contain an isopeptide bond that forms slowly over time in the recombinant protein. Given its structural context, this provides insight into the relationship between internal isopeptide-bond formation and pilus assembly. The Gram-positive organism Corynebacterium diphtheriae, the cause of diphtheria in humans, expresses pili on its surface which it uses for adhesion and colonization of its host. These pili are covalent protein polymers composed of three types of pilin subunit that are assembled by specific sortase enzymes. A structural analysis of the major pilin SpaD, which forms the polymeric backbone of one of the three types of pilus expressed by C. diphtheriae, is reported. Mass-spectral and crystallographic analysis shows that SpaD contains three internal Lys–Asn isopeptide bonds. One of these, shown by mass spectrometry to be located in the N-terminal D1 domain of the protein, only forms slowly, implying an energy barrier to bond formation. Two crystal structures, of the full-length three-domain protein at 2.5 Å resolution and of a two-domain (D2-D3) construct at 1.87 Å resolution, show that each of the three Ig-like domains contains a single Lys–Asn isopeptide-bond cross-link, assumed to give mechanical stability as in other such pili. Additional stabilizing features include a disulfide bond in the D3 domain and a calcium-binding loop in D2. The N-terminal D1 domain is more flexible than the others and, by analogy with other major pilins of this type, the slow formation of its isopeptide bond can be attributed to its location adjacent to the lysine used in sortase-mediated polymerization during pilus assembly.

  8. Crystal Structure of DsbA from Corynebacterium diphtheriae and Its Functional Implications for CueP in Gram-Positive Bacteria.

    Science.gov (United States)

    Um, Si-Hyeon; Kim, Jin-Sik; Song, Saemee; Kim, Nam Ah; Jeong, Seong Hoon; Ha, Nam-Chul

    2015-08-01

    In Gram-negative bacteria in the periplasmic space, the dimeric thioredoxin-fold protein DsbC isomerizes and reduces incorrect disulfide bonds of unfolded proteins, while the monomeric thioredoxin-fold protein DsbA introduces disulfide bonds in folding proteins. In the Gram-negative bacteria Salmonella enterica serovar Typhimurium, the reduced form of CueP scavenges the production of hydroxyl radicals in the copper-mediated Fenton reaction, and DsbC is responsible for keeping CueP in the reduced, active form. Some DsbA proteins fulfill the functions of DsbCs, which are not present in Gram-positive bacteria. In this study, we identified a DsbA homologous protein (CdDsbA) in the Corynebacterium diphtheriae genome and determined its crystal structure in the reduced condition at 1.5 Å resolution. CdDsbA consists of a monomeric thioredoxin-like fold with an inserted helical domain and unique N-terminal extended region. We confirmed that CdDsbA has disulfide bond isomerase/reductase activity, and we present evidence that the N-terminal extended region is not required for this activity and folding of the core DsbA-like domain. Furthermore, we found that CdDsbA could reduce CueP from C. diphtheriae.

  9. A slow-forming isopeptide bond in the structure of the major pilin SpaD from Corynebacterium diphtheriae has implications for pilus assembly.

    Science.gov (United States)

    Kang, Hae Joo; Paterson, Neil G; Kim, Chae Un; Middleditch, Martin; Chang, Chungyu; Ton-That, Hung; Baker, Edward N

    2014-05-01

    The Gram-positive organism Corynebacterium diphtheriae, the cause of diphtheria in humans, expresses pili on its surface which it uses for adhesion and colonization of its host. These pili are covalent protein polymers composed of three types of pilin subunit that are assembled by specific sortase enzymes. A structural analysis of the major pilin SpaD, which forms the polymeric backbone of one of the three types of pilus expressed by C. diphtheriae, is reported. Mass-spectral and crystallographic analysis shows that SpaD contains three internal Lys-Asn isopeptide bonds. One of these, shown by mass spectrometry to be located in the N-terminal D1 domain of the protein, only forms slowly, implying an energy barrier to bond formation. Two crystal structures, of the full-length three-domain protein at 2.5 Å resolution and of a two-domain (D2-D3) construct at 1.87 Å resolution, show that each of the three Ig-like domains contains a single Lys-Asn isopeptide-bond cross-link, assumed to give mechanical stability as in other such pili. Additional stabilizing features include a disulfide bond in the D3 domain and a calcium-binding loop in D2. The N-terminal D1 domain is more flexible than the others and, by analogy with other major pilins of this type, the slow formation of its isopeptide bond can be attributed to its location adjacent to the lysine used in sortase-mediated polymerization during pilus assembly.

  10. Novel hemin binding domains in the Corynebacterium diphtheriae HtaA protein interact with hemoglobin and are critical for heme iron utilization by HtaA.

    Science.gov (United States)

    Allen, Courtni E; Schmitt, Michael P

    2011-10-01

    The human pathogen Corynebacterium diphtheriae utilizes hemin and hemoglobin as iron sources for growth in iron-depleted environments. The use of hemin iron in C. diphtheriae involves the dtxR- and iron-regulated hmu hemin uptake locus, which encodes an ABC hemin transporter, and the surface-anchored hemin binding proteins HtaA and HtaB. Sequence analysis of HtaA and HtaB identified a conserved region (CR) of approximately 150 amino acids that is duplicated in HtaA and present in a single copy in HtaB. The two conserved regions in HtaA, designated CR1 and CR2, were used to construct glutathione S-transferase (GST) fusion proteins (GST-CR1 and GST-CR2) to assess hemin binding by UV-visual spectroscopy. These studies showed that both domains were able to bind hemin, suggesting that the conserved sequences are responsible for the hemin binding property previously ascribed to HtaA. HtaA and the CR2 domain were also shown to be able to bind hemoglobin (Hb) by the use of an enzyme-linked immunosorbent assay (ELISA) method in which Hb was immobilized on a microtiter plate. The CR1 domain exhibited a weak interaction with Hb in the ELISA system, while HtaB showed no significant binding to Hb. Competitive binding studies demonstrated that soluble hemin and Hb were able to inhibit the binding of HtaA and the CR domains to immobilized Hb. Moreover, HtaA was unable to bind to Hb from which the hemin had been chemically removed. Alignment of the amino acid sequences of CR domains from various Corynebacterium species revealed several conserved residues, including two highly conserved tyrosine (Y) residues and one histidine (H) residue. Site-directed mutagenesis studies showed that Y361 and H412 were critical for the binding to hemin and Hb by the CR2 domain. Biological assays showed that Y361 was essential for the hemin iron utilization function of HtaA. Hemin transfer experiments demonstrated that HtaA was able to acquire hemin from Hb and that hemin bound to HtaA could be

  11. Oral immunogenicity of tomato-derived sDPT polypeptide containing Corynebacterium diphtheriae, Bordetella pertussis and Clostridium tetani exotoxin epitopes.

    Science.gov (United States)

    Soria-Guerra, Ruth E; Rosales-Mendoza, Sergio; Moreno-Fierros, Leticia; López-Revilla, Rubén; Alpuche-Solís, Angel G

    2011-03-01

    DPT vaccine, designed to immunize against diphtheria, pertussis, and tetanus, has been shown to be effective in humans. Nevertheless, dissatisfaction with the whole-cell preparations is due to the reactogenicity, which has to lead to the development of new safer formulations. Previously, we described the expression in tomato of a plant-optimized synthetic gene encoding the recombinant polypeptide sDPT, containing mainly immunoprotective epitopes of the diphtheria, pertussis and tetanus exotoxins and two adjuvants. In this study, we examined whether the ingestion of tomato-derived sDPT protein induces specific antibodies in mice after three weekly doses scheme. A positive group immunized with DPT toxoids was included. Specific antibody levels were assessed in serum, gut and lung. Sera tested for IgG antibody response to pertussis, tetanus and diphtheria toxin showed responses to the foreign antigens; interestingly, the response to diphtheria epitope was similar to those observed in the positive group. We found higher IgG1 than IgG2a responses in serum. A modest IgG response was observed in the tracheopulmonary fluid. High response of IgA against tetanus toxin was evident in gut, which was statistically comparable to that obtained in the positive group. The levels of response in these groups were higher than those in mice that received wild-type tomato. These findings support the concept of using transgenic tomatoes expressing sDPT polypeptide as model for edible vaccine against diphtheria, pertussis, and tetanus.

  12. Analysis of Corynebacterium diphtheriae macrophage interaction: Dispensability of corynomycolic acids for inhibition of phagolysosome maturation and identification of a new gene involved in synthesis of the corynomycolic acid layer.

    Science.gov (United States)

    Ott, Lisa; Hacker, Elena; Kunert, Timo; Karrington, Ian; Etschel, Philipp; Lang, Roland; Wiesmann, Veit; Wittenberg, Thomas; Singh, Albel; Varela, Cristian; Bhatt, Apoorva; Sangal, Vartul; Burkovski, Andreas

    2017-01-01

    Corynebacterium diphtheriae is the causative agent of diphtheria, a toxin mediated disease of upper respiratory tract, which can be fatal. As a member of the CMNR group, C. diphtheriae is closely related to members of the genera Mycobacterium, Nocardia and Rhodococcus. Almost all members of these genera comprise an outer membrane layer of mycolic acids, which is assumed to influence host-pathogen interactions. In this study, three different C. diphtheriae strains were investigated in respect to their interaction with phagocytic murine and human cells and the invertebrate infection model Caenorhabditis elegans. Our results indicate that C. diphtheriae is able to delay phagolysosome maturation after internalization in murine and human cell lines. This effect is independent of the presence of mycolic acids, as one of the strains lacked corynomycolates. In addition, analyses of NF-κB induction revealed a mycolate-independent mechanism and hint to detrimental effects of the different strains tested on the phagocytic cells. Bioinformatics analyses carried out to elucidate the reason for the lack of mycolates in one of the strains led to the identification of a new gene involved in mycomembrane formation in C. diphtheriae.

  13. The ChrSA and HrrSA Two-Component Systems Are Required for Transcriptional Regulation of the hemA Promoter in Corynebacterium diphtheriae

    Science.gov (United States)

    Burgos, Jonathan M.

    2016-01-01

    ABSTRACT Corynebacterium diphtheriae utilizes heme and hemoglobin (Hb) as iron sources for growth in low-iron environments. In C. diphtheriae, the two-component signal transduction systems (TCSs) ChrSA and HrrSA are responsive to Hb levels and regulate the transcription of promoters for hmuO, hrtAB, and hemA. ChrSA and HrrSA activate transcription at the hmuO promoter and repress transcription at hemA in an Hb-dependent manner. In this study, we show that HrrSA is the predominant repressor at hemA and that its activity results in transcriptional repression in the presence and absence of Hb, whereas repression of hemA by ChrSA is primarily responsive to Hb. DNA binding studies showed that both ChrA and HrrA bind to the hemA promoter region at virtually identical sequences. ChrA binding was enhanced by phosphorylation, while binding to DNA by HrrA was independent of its phosphorylation state. ChrA and HrrA are phosphorylated in vitro by the sensor kinase ChrS, whereas no kinase activity was observed with HrrS in vitro. Phosphorylated ChrA was not observed in vivo, even in the presence of Hb, which is likely due to the instability of the phosphate moiety on ChrA. However, phosphorylation of HrrA was observed in vivo regardless of the presence of the Hb inducer, and genetic analysis indicates that ChrS is responsible for most of the phosphorylation of HrrA in vivo. Phosphorylation studies strongly suggest that HrrS functions primarily as a phosphatase and has only minimal kinase activity. These findings collectively show a complex mechanism of regulation at the hemA promoter, where both two-component systems act in concert to optimize expression of heme biosynthetic enzymes. IMPORTANCE Understanding the mechanism by which two-component signal transduction systems function to respond to environmental stimuli is critical to the study of bacterial pathogenesis. The current study expands on the previous analyses of the ChrSA and HrrSA TCSs in the human pathogen C

  14. The ChrA response regulator in Corynebacterium diphtheriae controls hemin-regulated gene expression through binding to the hmuO and hrtAB promoter regions.

    Science.gov (United States)

    Burgos, Jonathan M; Schmitt, Michael P

    2012-04-01

    Corynebacterium diphtheriae, the etiologic agent of diphtheria, utilizes heme and hemoglobin (Hb) as iron sources for growth. Heme-iron utilization involves HmuO, a heme oxygenase that degrades cytosolic heme, resulting in the release of heme-associated iron. Expression of the hmuO promoter is under dual regulation, in which transcription is repressed by DtxR and iron and activated by a heme source, such as hemin or Hb. Hemin-dependent activation is mediated primarily by the ChrAS two-component system, in which ChrS is a putative heme-responsive sensor kinase while ChrA is proposed to serve as a response regulator that activates transcription. It was recently shown that the ChrAS system similarly regulates the hrtAB genes, which encode an ABC transporter involved in the protection of C. diphtheriae from hemin toxicity. In this study, we characterized the phosphorelay mechanism in the ChrAS system and provide evidence for the direct regulation of the hmuO and hrtAB promoters by ChrA. A fluorescence staining method was used to show that ChrS undergoes autophosphorylation and that the phosphate moiety is subsequently transferred to ChrA. Promoter fusion studies identified regions upstream of the hmuO and hrtAB promoters that are critical for the heme-dependent regulation by ChrA. Electrophoretic mobility shift assays revealed that ChrA specifically binds at the hmuO and hrtAB promoter regions and that binding is phosphorylation dependent. A phosphorylation-defective mutant of ChrA [ChrA(D50A)] exhibited significantly diminished binding to the hmuO promoter region relative to that of wild-type ChrA. DNase I footprint analysis further defined the sequences in the hmuO and hrtAB promoters that are involved in ChrA binding, and this analysis revealed that the DtxR binding site at the hmuO promoter partially overlaps the binding site for ChrA. DNase I protection studies as well as promoter fusion analysis suggest that ChrA and DtxR compete for binding at the hmuO promoter

  15. Conservación por congelación de Bordetella pertussis y Corynebacterium diphtheriae, empleados en la producción de vacunas para uso humano

    Directory of Open Access Journals (Sweden)

    Yilian Plasencia,

    2000-11-01

    Full Text Available En el presente estudio se evaluó el método de congelación a –70ºC para la preservación de Bordetella pertussis y Corynebacterium diphtheriae. Para verificar el sustento de los cultivos se realizó un adecuado control de calidad, que incluyó comprobación de pureza, viabilidad y estabilidad de las propiedades de interés. En este trabajo se probaron diferentes formulaciones. Se seleccionó la que arrojó los mejores resultados y se realizó un estudio de mantenimiento de las características evaluadas durante el tiempo. Para medir determinados parámetros se realizaron procesos a escala industrial, empleándose para esto un biorreactor Chemap de 35 L. Se tomaron como referencia los valores obtenidos por las cepas conservadas por liofilización. De esta forma se buscaron alternativas y soluciones a problemas presentados en su conservación. Los resultados obtenidos sugieren la posible inclusión en el Programa de Mantenimiento establecido.

  16. Role of active-site residues Tyr55 and Tyr114 in catalysis and substrate specificity of Corynebacterium diphtheriae C-S lyase.

    Science.gov (United States)

    Astegno, Alessandra; Allegrini, Alessandra; Piccoli, Stefano; Giorgetti, Alejandro; Dominici, Paola

    2015-01-01

    In recent years, there has been increased interest in bacterial methionine biosynthesis enzymes as antimicrobial targets because of their pivotal role in cell metabolism. C-S lyase from Corynebacterium diphtheriae is a pyridoxal 5'-phosphate-dependent enzyme in the transsulfuration pathway that catalyzes the α,β-elimination of sulfur-containing amino acids, such as L-cystathionine, to generate ammonia, pyruvate, and homocysteine, the immediate precursor of L-methionine. In order to gain deeper insight into the functional and dynamic properties of the enzyme, mutants of two highly conserved active-site residues, Y55F and Y114F, were characterized by UV-visible absorbance, fluorescence, and CD spectroscopy in the absence and presence of substrates and substrate analogs, as well as by steady-state kinetic studies. Substitution of Tyr55 with Phe apparently causes a 130-fold decrease in K(d)(PLP) at pH 8.5 providing evidence that Tyr55 plays a role in cofactor binding. Moreover, spectral data show that the mutant accumulates the external aldimine intermediate suggesting that the absence of interaction between the hydroxyl moiety and PLP-binding residue Lys222 causes a decrease in the rate of substrate deprotonation. Mutation of Tyr114 with Phe slightly influences hydrolysis of L-cystathionine, and causes a change in substrate specificity towards L-serine and O-acetyl-L-serine compared to the wild type enzyme. These findings, together with computational data, provide useful insights in the substrate specificity of C-S lyase, which seems to be regulated by active-site architecture and by the specific conformation in which substrates are bound, and will aid in development of inhibitors.

  17. Identification of non-diphtheriae corynebacterium by use of matrix-assisted laser desorption ionization-time of flight mass spectrometry.

    Science.gov (United States)

    Alatoom, Adnan A; Cazanave, Charles J; Cunningham, Scott A; Ihde, Sherry M; Patel, Robin

    2012-01-01

    We evaluated the Bruker Biotyper matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry for identification of 92 clinical isolates of Corynebacterium species in comparison to identification using rpoB or 16S rRNA gene sequencing. Eighty isolates (87%) yielded a score of ≥1.700, and all of these were correctly identified to the species level with the exception of Corynebacterium aurimucosum being misidentified as the closely related Corynebacterium minutissimum.

  18. Diphtheria: forgotten, but not gone.

    Science.gov (United States)

    Adler, N R; Mahony, A; Friedman, N D

    2013-02-01

    Diphtheria is an acute, highly infectious, vaccine-preventable and previously endemic disease whose etiologic agent is Corynebacterium diphtheriae. Diphtheria may manifest as an upper respiratory tract infection, a cutaneous infection or as an asymptomatic carrier state. The most common sites of infection are the pharynx and the tonsils, with common clinical manifestations that include sore throat, malaise, cervical lymphadenopathy and low-grade fever. Absorption and dissemination of C. diphtheriae from the respiratory tract can cause disseminated infection and may lead to cardiac or neurological toxicity. The cornerstone of treatment for diphtheria is diphtheria antitoxin. Early treatment is critical as the degree of protection is inversely proportional to the duration of the illness before its administration. Routine childhood vaccination virtually eliminated diphtheria in most industrialised countries. However, in the pre-vaccination era, diphtheria was the most common infectious cause of death in Australia. A case of diphtheria in Brisbane in April 2011 and two recent positive cultures in regional Victoria underscore the need for heightened awareness of C. diphtheriae as an important pathogen. In order to prevent the re-emergence of diphtheria in Australia, public health measures are required to increase immunity in early school leavers and the adult population, and to ensure that travellers to endemic regions are fully immunised. Health policy-makers and clinicians alike should not underestimate the importance of primary vaccination and booster vaccination against diphtheria among healthy adults and travellers. © 2013 The Authors; Internal Medicine Journal © 2013 Royal Australasian College of Physicians.

  19. The ABC transporter HrtAB confers resistance to hemin toxicity and is regulated in a hemin-dependent manner by the ChrAS two-component system in Corynebacterium diphtheriae.

    Science.gov (United States)

    Bibb, Lori A; Schmitt, Michael P

    2010-09-01

    Corynebacterium diphtheriae, the causative agent of the severe respiratory disease diphtheria, utilizes hemin and hemoglobin as iron sources for growth in iron-depleted environments. Because of the toxicity of high levels of hemin and iron, these compounds are often tightly regulated in bacterial systems. In this report, we identify and characterize the C. diphtheriae hrtAB genes, which encode a putative ABC type transporter involved in conferring resistance to the toxic effects of hemin. Deletion of the hrtAB genes in C. diphtheriae produced increased sensitivity to hemin, which was complemented by a plasmid harboring the cloned hrtAB locus. The HrtAB system was not involved in the uptake and use of hemin as an iron source. The hrtAB genes are located on the C. diphtheriae genome upstream from the chrSA operon, which encodes a previously characterized two-component signal transduction system that regulates gene expression in a heme-dependent manner. The hrtB promoter is activated by the ChrAS system in the presence of hemin or hemoglobin, and mutations in the chrSA genes abolish heme-activated expression from the hrtB promoter. It was also observed that transcription from the hrtB promoter is reduced in a dtxR deletion mutant, suggesting that DtxR is required for optimal expression of hrtAB. Previous studies proposed that the ChrS sensor kinase may be responsive to an environmental signal, such as hemin. We show that specific point mutations in the ChrS N-terminal transmembrane domain result in a reduced ability to activate the hrtB promoter in the presence of a heme source, suggesting that this putative sensor region is essential for the detection of a signal produced in response to hemin exposure. This study shows that the HrtAB system is required for protection from hemin toxicity and that expression of the hrtAB genes is regulated by the ChrAS two-component system. This study demonstrates a direct correlation between the detection of heme or a heme

  20. Identification of a Human Monoclonal Antibody To Replace Equine Diphtheria Antitoxin for Treatment of Diphtheria Intoxication

    OpenAIRE

    Sevigny, Leila M; Booth, Brian J.; Rowley, Kirk J.; Leav, Brett A.; Cheslock, Peter S.; Kerry A Garrity; Sloan, Susan E.; Thomas, William; Babcock, Gregory J.; Wang, Yang

    2013-01-01

    Diphtheria antitoxin (DAT) has been the cornerstone of the treatment of Corynebacterium diphtheriae infection for more than 100 years. Although the global incidence of diphtheria has declined steadily over the last quarter of the 20th century, the disease remains endemic in many parts of the world, and significant outbreaks still occur. DAT is an equine polyclonal antibody that is not commercially available in the United States and is in short supply globally. A safer, more readily available ...

  1. Diphtheria Complications

    Science.gov (United States)

    ... Search Form Controls Cancel Submit Search The CDC Diphtheria Note: Javascript is disabled or is not supported ... message, please visit this page: About CDC.gov . Diphtheria Home About Diphtheria Causes and Transmission Symptoms Complications ...

  2. Diphtheria Symptoms

    Science.gov (United States)

    ... Search Form Controls Cancel Submit Search The CDC Diphtheria Note: Javascript is disabled or is not supported ... message, please visit this page: About CDC.gov . Diphtheria Home About Diphtheria Causes and Transmission Symptoms Complications ...

  3. Diphtheria immunity status in Egypt.

    Science.gov (United States)

    Redwan, El-Rashdy M; El-Awady, Mostafa K

    2004-01-01

    The aim of this study was to determine immune status to corynebacterium diphtheria by screening for protective antibodies in a sample of Egyptian population. The study population consisted of 709 healthy subjects aged from 2 months to 105 years, inhabitants of 6 regions of Egypt. The study utilized Enzyme linked immunosorbent assay (ELISA) to measure serum levels IgG antibodies reactive with diphtheria toxoid. Levels of diphtheria toxoid antibody > or = 0.1 IU/ ml were defined as immune/protected, 23.9 % of the population were found to be susceptible to diphtheria (IgG level antibodies decreased in old ages (< 60 y) with the females being more susceptible then males. These results recommend a booster immunization for the susceptible age groups.

  4. Diphtheria: a zoonotic disease in France?

    Science.gov (United States)

    Bonmarin, Isabelle; Guiso, Nicole; Le Flèche-Matéos, Anne; Patey, Olivier; Patrick, A D Grimont; Levy-Bruhl, Daniel

    2009-06-24

    Thanks to vaccination, diphtheria has almost disappeared in France. The case definition, used for mandatory notification, was expanded in 2003 to include toxin-producing strains of Corynebacterium ulcerans. We describe the epidemiology of diphtheria in France from 1990 to 2008. No cases occurred between 1990 and 2001. Since 2002, 19 cases have been reported: 4 cases due to Corynebacterium diphtheriae related to exposure in endemic countries, and 15 cases due to other corynebacteria, including 4 cases of pseudomembranous pharyngitis, mainly related to contact with domestic animals. High vaccination coverage in the population and sensitive surveillance need to be maintained. Moreover, control measures need to be adapted to the non-C. diphtheriae toxigenic species.

  5. A fatal case of urosepsis due to Corynebacterium riegelii

    Directory of Open Access Journals (Sweden)

    Gokhan Aygun

    2013-01-01

    Full Text Available Corynebacterium species other than Corynebacterium diphtheriae rarely cause infections in human but rather reside in flora, however they have been reported to cause opportunistic infections in both immunocompromised and immunecompetent patients. Here we report for the first time a case of an elderly female patient presenting with a fatal urosepsis caused by a recently defined pathogen, Corynebacterium riegelii, identified on second day after patient hospitalization leading to a progressive worsening and death of the patient on 6th day.

  6. A fatal case of urosepsis due to Corynebacterium riegelii.

    Science.gov (United States)

    Aygun, Gokhan; Midilli, Kenan; Cilingir, Hatice; Yilmaz, Mesut; Kutukcu, Aysegul; Eker, Engin

    2013-01-01

    Corynebacterium species other than Corynebacterium diphtheriae rarely cause infections in human but rather reside in flora, however they have been reported to cause opportunistic infections in both immunocompromised and immunecompetent patients. Here we report for the first time a case of an elderly female patient presenting with a fatal urosepsis caused by a recently defined pathogen, Corynebacterium riegelii, identified on second day after patient hospitalization leading to a progressive worsening and death of the patient on 6th day.

  7. Diphtheria Photos

    Science.gov (United States)

    ... Polio Whooping cough Influenza (flu) Rabies Yellow fever Diphtheria Photos Photographs accompanied by text that reads "Courtesy ... and Prevention 10-year-old child with severe diphtheria www.vaccineinformation.org/photos/diphcdc002a.jpg Courtesy of ...

  8. Solution 1H NMR investigation of the active site molecular and electronic structures of substrate-bound, cyanide-inhibited HmuO, a bacterial heme oxygenase from Corynebacterium diphtheriae.

    Science.gov (United States)

    Li, Yiming; Syvitski, Ray T; Chu, Grace C; Ikeda-Saito, Masao; Mar, Gerd N La

    2003-02-28

    The molecular structure and dynamic properties of the active site environment of HmuO, a heme oxygenase (HO) from the pathogenic bacterium Corynebacterium diphtheriae, have been investigated by (1)H NMR spectroscopy using the human HO (hHO) complex as a homology model. It is demonstrated that not only the spatial contacts among residues and between residues and heme, but the magnetic axes that can be related to the direction and magnitude of the steric tilt of the FeCN unit are strongly conserved in the two HO complexes. The results indicate that very similar contributions of steric blockage of several meso positions and steric tilt of the attacking ligand are operative. A distal H-bond network that involves numerous very strong H-bonds and immobilized water molecules is identified in HmuO that is analogous to that previously identified in hHO (Li, Y., Syvitski, R. T., Auclair, K., Wilks, A., Ortiz de Montellano, P. R., and La Mar, G. N. (2002) J. Biol. Chem. 277, 33018-33031). The NMR results are completely consistent with the very recent crystal structure of the HmuO.substrate complex. The H-bond network/ordered water molecules are proposed to orient the distal water molecule near the catalytically key Asp(136) (Asp(140) in hHO) that stabilizes the hydroperoxy intermediate. The dynamic stability of this H-bond network in HmuO is significantly greater than in hHO and may account for the slower catalytic rate in bacterial HO compared with mammalian HO.

  9. Structures of the substrate-free and product-bound forms of HmuO, a heme oxygenase from corynebacterium diphtheriae: x-ray crystallography and molecular dynamics investigation.

    Science.gov (United States)

    Unno, Masaki; Ardèvol, Albert; Rovira, Carme; Ikeda-Saito, Masao

    2013-11-29

    Heme oxygenase catalyzes the degradation of heme to biliverdin, iron, and carbon monoxide. Here, we present crystal structures of the substrate-free, Fe(3+)-biliverdin-bound, and biliverdin-bound forms of HmuO, a heme oxygenase from Corynebacterium diphtheriae, refined to 1.80, 1.90, and 1.85 Å resolution, respectively. In the substrate-free structure, the proximal and distal helices, which tightly bracket the substrate heme in the substrate-bound heme complex, move apart, and the proximal helix is partially unwound. These features are supported by the molecular dynamic simulations. The structure implies that the heme binding fixes the enzyme active site structure, including the water hydrogen bond network critical for heme degradation. The biliverdin groups assume the helical conformation and are located in the heme pocket in the crystal structures of the Fe(3+)-biliverdin-bound and the biliverdin-bound HmuO, prepared by in situ heme oxygenase reaction from the heme complex crystals. The proximal His serves as the Fe(3+)-biliverdin axial ligand in the former complex and forms a hydrogen bond through a bridging water molecule with the biliverdin pyrrole nitrogen atoms in the latter complex. In both structures, salt bridges between one of the biliverdin propionate groups and the Arg and Lys residues further stabilize biliverdin at the HmuO heme pocket. Additionally, the crystal structure of a mixture of two intermediates between the Fe(3+)-biliverdin and biliverdin complexes has been determined at 1.70 Å resolution, implying a possible route for iron exit.

  10. Respiratory diphtheria in an asylum seeker from Afghanistan arriving to Finland via Sweden, December 2015.

    Science.gov (United States)

    Sane, Jussi; Sorvari, Tiina; Widerström, Micael; Kauma, Heikki; Kaukoniemi, Ulla; Tarkka, Eveliina; Puumalainen, Taneli; Kuusi, Markku; Salminen, Mika; Lyytikäinen, Outi

    2016-01-01

    In December 2015, an asylum seeker originating from Afghanistan was diagnosed with respiratory diphtheria in Finland. He arrived in Finland from Sweden where he had already been clinically suspected and tested for diphtheria. Corynebacterium diphtheriae was confirmed in Sweden and shown to be genotypically and phenotypically toxigenic. The event highlights the importance of early case detection, rapid communication within the country and internationally as well as preparedness plans of diphtheria antitoxin availability.

  11. Characterization of a Mutant Diphtheria Toxin that is Defective in Binding to Cell Membrane Receptors on Vero Cells

    Science.gov (United States)

    1982-08-13

    R.K. , and Barksdale, L. (1969) Genetic analysis of tox"*" and tox bacteriophages of Corynebacterium diphtheriae . J. Virol. _3. 586-598 76. Holmes...A sensitive cytotoxicity assay was used to screen the supernatants of cultures of Corynebacterium diphtheriae that were Infected with the...beads were coupled to diphtheria toxin and were incubated with resistant mouse macrophages or with sensitive guinea pig macrophages . Although both

  12. IMMUNOBIOLOGY OF DIPHTHERIA. RECENT APPROACHES FOR THE PREVENTION, DIAGNOSIS, AND TREATMENT OF DISEASE

    Directory of Open Access Journals (Sweden)

    D. V. Kolybo

    2013-08-01

    Full Text Available Diphtheria is a highly contagious life-threatening disease caused by the toxi genic strains of Corynebacterium diphtheria, which are transformed by a bacteriophage carrying the toxin gene. Diphtheria causative agent and its major virulence factor diphtheria toxin are well studied, but outbreaks of disease still occur worldwide. Rapid development of new methods in immunology and molecular biology is currently leading to improvement of prophylaxis, diagnosis and treatment of diphtheria. This review highlights the microbiological, epidemiological and immunological aspects of diphtheria infection, role of diphtheria toxin and others virulence factors in diphtheria pathogenesis and role of humoral anti-toxic immunity in the protection against disease. Perspectives in development of new diagnostic tests, anti-diphtheria vaccines, immunobiological preparations and antidotes for prevention of diphtheria infection, and other anti-diphteria means was also discussed.

  13. Diphtheria in Europe: current problems and new challenges.

    Science.gov (United States)

    Zakikhany, Katherina; Efstratiou, Androulla

    2012-05-01

    Diphtheria, caused by toxigenic strains of Corynebacterium diphtheriae, is an ancient disease with high incidence and mortality that has always been characterized by epidemic waves of occurrence. Whilst towards the beginning of the 1980s, many European countries were progressing towards the elimination of diphtheria, an epidemic re-emergence of diphtheria in the Russian Federation and the Newly Independent States of the former Soviet Union demonstrated a continuous threat of the disease into the 1990s. At present, the epidemic is under control and only sporadic cases are observed in Europe. However, the circulation of toxigenic strains is still observed in all parts of the world, posing a constant threat to the population with low levels of seroprotection. More recently, Corynebacterium ulcerans has been increasingly isolated as emerging zoonotic agent of diphtheria from companion animals such as cats or dogs, indicating the enduring threat of this thought-to-be controlled disease.

  14. [Cutaneous diphtheria after a minor injury in Sri Lanka].

    Science.gov (United States)

    Berg, L; Mechlin, A; Schultz, E S

    2016-02-01

    Cutaneous dipththeria is an infectious bacterial disease endemic in tropical regions, but rarely diagnosed in Germany. Following travel in Sri Lanka, a 60-year-old German presented to our dermatological clinic with a skin ulcer and extensive erythematous erosive edema of his left foot. Corynebacterium diphtheriae was isolated from a swab of the lesion. There were no clinical signs of toxic diphtheria. The patient was treated with penicillin G and erythromycin, followed by a slow healing of the lesion. The isolated strain could be identified as toxigenic C. diphtheriae mitis. Due to increased travel activity, dermatologists should have uncommon infections like cutaneous diphtheria in mind.

  15. Diphtheria in the Postepidemic Period, Europe, 2000–2009

    Science.gov (United States)

    White, Joanne M.; Lucenko, Irina; Mercer, David; Crowcroft, Natasha S.; Neal, Shona; Efstratiou, Androulla

    2012-01-01

    Diphtheria incidence has decreased in Europe since its resurgence in the 1990s, but circulation continues in some countries in eastern Europe, and sporadic cases have been reported elsewhere. Surveillance data from Diphtheria Surveillance Network countries and the World Health Organization European Region for 2000–2009 were analyzed. Latvia reported the highest annual incidence in Europe each year, but the Russian Federation and Ukraine accounted for 83% of all cases. Over the past 10 years, diphtheria incidence has decreased by >95% across the region. Although most deaths occurred in disease-endemic countries, case-fatality rates were highest in countries to which diphtheria is not endemic, where unfamiliarity can lead to delays in diagnosis and treatment. In western Europe, toxigenic Corynebacterium ulcerans has increasingly been identified as the etiologic agent. Reduction in diphtheria incidence over the past 10 years is encouraging, but maintaining high vaccination coverage is essential to prevent indigenous C. ulcerans and reemergence of C. diphtheriae infections. PMID:22304732

  16. Diphtheria in the postepidemic period, Europe, 2000-2009.

    Science.gov (United States)

    Wagner, Karen S; White, Joanne M; Lucenko, Irina; Mercer, David; Crowcroft, Natasha S; Neal, Shona; Efstratiou, Androulla

    2012-02-01

    Diphtheria incidence has decreased in Europe since its resurgence in the 1990s, but circulation continues in some countries in eastern Europe, and sporadic cases have been reported elsewhere. Surveillance data from Diphtheria Surveillance Network countries and the World Health Organization European Region for 2000-2009 were analyzed. Latvia reported the highest annual incidence in Europe each year, but the Russian Federation and Ukraine accounted for 83% of all cases. Over the past 10 years, diphtheria incidence has decreased by >95% across the region. Although most deaths occurred in disease-endemic countries, case-fatality rates were highest in countries to which diphtheria is not endemic, where unfamiliarity can lead to delays in diagnosis and treatment. In western Europe, toxigenic Corynebacterium ulcerans has increasingly been identified as the etiologic agent. Reduction in diphtheria incidence over the past 10 years is encouraging, but maintaining high vaccination coverage is essential to prevent indigenous C. ulcerans and reemergence of C. diphtheriae.

  17. An isolated outbreak of diphtheria in South Africa, 2015.

    Science.gov (United States)

    Mahomed, S; Archary, M; Mutevedzi, P; Mahabeer, Y; Govender, P; Ntshoe, G; Kuhn, W; Thomas, J; Olowolagba, A; Blumberg, L; McCarthy, K; Mlisana, K; DU Plessis, M; VON Gottberg, A; Moodley, P

    2017-07-01

    An outbreak of respiratory diphtheria occurred in two health districts in the province of KwaZulu-Natal in South Africa in 2015. A multidisciplinary outbreak response team was involved in the investigation and management of the outbreak. Fifteen cases of diphtheria were identified, with ages ranging from 4 to 41 years. Of the 12 cases that were under the age of 18 years, 9 (75%) were not fully immunized for diphtheria. The case fatality was 27%. Ninety-three household contacts, 981 school or work contacts and 595 healthcare worker contacts were identified and given prophylaxis against Corynebacterium diphtheriae infection. A targeted vaccination campaign for children aged 6-15 years was carried out at schools in the two districts. The outbreak highlighted the need to improve diphtheria vaccination coverage in the province and to investigate the feasibility of offering diphtheria vaccines to healthcare workers.

  18. Diphtheria (For Parents)

    Science.gov (United States)

    ... Your Child Natural Disasters: How Families Can Help Diphtheria KidsHealth > For Parents > Diphtheria Print A A A ... Contagiousness Treatment When to Call the Doctor About Diphtheria Diphtheria is a bacterial infection that spreads easily ...

  19. Corynebacterium ulcerans, an emerging human pathogen.

    Science.gov (United States)

    Hacker, Elena; Antunes, Camila A; Mattos-Guaraldi, Ana L; Burkovski, Andreas; Tauch, Andreas

    2016-09-01

    While formerly known infections of Corynebacterium ulcerans are rare and mainly associated with contact to infected cattle, C. ulcerans has become an emerging pathogen today. In Western Europe, cases of respiratory diphtheria caused by C. ulcerans have been reported more often than infections by Corynebacterium diphtheria, while systemic infections are also increasingly reported. Little is known about factors that contribute to host colonization and virulence of this zoonotic pathogen. Research in this field has received new impetus by the publication of several C. ulcerans genome sequences in the past years. This review gives a comprehensive overview of the basic knowledge of C. ulcerans, as well as the recent advances made in the analysis of putative virulence factors.

  20. Cases of cutaneous diphtheria in New Zealand: implications for surveillance and management.

    Science.gov (United States)

    Sears, Ann; McLean, Margot; Hingston, David; Eddie, Barbara; Short, Pat; Jones, Mark

    2012-02-24

    Diphtheria is an acute bacterial illness caused by toxigenic strains of Corynebacterium diphtheriae (C. diphtheriae). We describe two epidemiologically-linked cases of skin infections from which toxigenic C. diphtheriae was isolated, and discuss implications for diphtheria surveillance and management in New Zealand. A public health investigation was undertaken to identify and manage close contacts of the index case. National and international guidelines on the surveillance and management of cutaneous diphtheria were reviewed, and data on toxigenic C. diphtheriae isolates identified in New Zealand from 1987-2009 were examined. The index case was an adult male who developed a cutaneous infection after being tattooed in Samoa. A wound swab taken from the infected tattoo grew a toxigenic strain of C. diphtheriae (var gravis). A secondary case of toxigenic cutaneous diphtheria was identified in a household contact. Instances of respiratory diphtheria associated with toxigenic cutaneous lesions have been reported in the literature. The review of surveillance data revealed inconsistencies in the notification of toxigenic strains of C. diphtheriae isolated from cutaneous sites. These cases are an important reminder that diphtheria remains a threat in New Zealand. All cases with toxigenic C. diphtheriae isolated from a clinical specimen, regardless of the site of infection, should be notified to a Medical Officer of Health.

  1. Diphtheria Diagnosis and Treatment

    Science.gov (United States)

    ... Search The CDC Cancel Submit Search The CDC Diphtheria Note: Javascript is disabled or is not supported ... message, please visit this page: About CDC.gov . Diphtheria Home About Diphtheria Causes and Transmission Symptoms Complications ...

  2. Molecular epidemiology of C. diphtheriae strains during different phases of the diphtheria epidemic in Belarus

    Directory of Open Access Journals (Sweden)

    Grimont Patrick AD

    2006-08-01

    Full Text Available Abstract Background The reemergence of epidemic diphtheria in Belarus in 1990s has provided us with important information on the biology of the disease and the diversity of the causative agent Corynebacterium diphtheriae. Molecular investigations were conducted with the aim to analyze the genetic variability of C diphtheriae during the post-epidemic period. Methods The biotype and toxigenicity status of 3513 C. diphtheriae strains isolated from all areas in Belarus during a declining period of diphtheria morbidity (1996–2005 was undertaken. Of these, 384 strains were isolated from diphtheria cases, 1968 from tonsillitis patients, 426 from contacts and 735 from healthy carriers. Four hundred and thirty two selected strains were ribotyped. Results The C diphtheriae gravis biotype, which was prevalent during 1996–2000, was "replaced" by the mitis biotype during 2001–2005. The distribution of toxigenic C. diphtheriae strains also decreased from 47.1% (1996 to 5.8% (2005. Changes in the distribution of the epidemic ribotypes Sankt-Peterburg and Rossija were also observed. During 2001–2005 the proportion of the Sankt-Peterburg ribotype decreased from 24.3% to 2.3%, in contrast to the Rossija ribotype, that increased from 25.1% to 49.1%. The circulation of other toxigenic ribotypes (Otchakov, Lyon, Bangladesh, which were prevalent during the period of high diphtheria incidence, also decreased. But at the same time, the proportion of non-toxigenic strains with the Cluj and Rossija ribotypes dramatically increased and accounted for 49.3% and 30.1%, respectively. Conclusion The decrease in morbidity correlated with the dramatic decrease in the isolation of the gravis biotype and Sankt Peterburg ribotype, and the prevalence of the Rossija ribotype along with other rare ribotypes associated with non-toxigenic strains (Cluj and Rossija, in particular.

  3. Diphtheria in Andhra Pradesh-a clinical-epidemiological study.

    Science.gov (United States)

    M, Meera; M, Rajarao

    2014-02-01

    Clinical diphtheria is on the increase worldwide, mainly affecting developing countries. We sought to understand its presentation among patients at Sir Ronald Ross Institute of Tropical and Communicable Diseases in Hyderabad, Andhra Pradesh, India. Diphtheria patients presented with fever, pharyngitis, and a patch in the throat. Data collected for each patient included age, clinical presentation, morbidity, mortality, bacteria isolated from culture, and immunization status. Of 61 950 admissions from January 2008 to December 2012, 2925 (4.7%) had clinical diphtheria; 1194 had been immunized and 1731 were non-immunized. Immunized patients had a milder disease. Culture-positive immunized patients were positive for Corynebacterium other than diphtheriae (COD; n=104) or Corynebacterium diphtheriae (CD; n=23); these patients suffered mild disease and recovered completely. In contrast, culture-positive non-immunized patients were positive for COD (n=11) or CD (n=412). Eighty-one patients (3%) died, 77 of whom were non-immunized; death was usually as a result of myocarditis. Seventy-three percent of deaths were in patients aged diphtheria and its severity and morbidity differ considerably in immunized and non-immunized patients. Disease caused by CD can be deadly, while disease due to COD is mild and responds to treatment. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. Diphtheria - 'The strangling angel' of children.

    Science.gov (United States)

    Byard, Roger W

    2013-02-01

    Diphtheria, an acute infectious condition caused by Corynebacterium diphtheriae, was once a major killer of children. Although the mortality rates dropped dramatically in the mid-twentieth century, due to a combination of improved standards of living and immunization programs, outbreaks are still occurring. Two children, aged four and five years respectively, are reported to demonstrate characteristic features of lethal cases. Death in case 1 was due to an extensive upper airway pseudomembrane causing acute respiratory failure. The diagnosis of diphtheria was only made at postmortem. Death in case 2 was due to acute cardiac failure with heart block complicating diphtheria. Other mechanisms in fatal cases involve disseminated intravascular coagulation, renal and endocrine failure. Declining levels of immunity among adults has resulted in a change in the epidemiological pattern of the disease with an older age of victims in recent outbreaks. As a result of population shifts and failure to immunize children it is likely that forensic pathologists may see more cases of diphtheria in the future. Due to the rarity of cases in Western communities and atypical presentations, the diagnosis may only be established at autopsy. Copyright © 2012 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  5. MODERN APPROACHES IN COMPLEX LABORATORY TESTING FOR DIPHTHERIA

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    L. A. Kraeva

    2012-01-01

    Full Text Available Abstract. The criteria of reliable validation of population protection against diphtheria on the base of two indices including quantity of antitoxic antibodies to diphtheria and avidity index have been established. For this purposes it was proposed to use the modified variant of ELISA allowed to detect both indices simultaneously. The formula of probable development of diphtheria in case of the close contact with patients or Corynebacterium diphtheriae bacteria carriers as well as determination of revaccination time have been proposed. The authors developed “The algorithm of population immunity control and assessment of non-susceptibility to diphtheria” and “The algorithm of micro biological testing of clinical samples for C. diphtheriae”.

  6. Identification of a human monoclonal antibody to replace equine diphtheria antitoxin for treatment of diphtheria intoxication.

    Science.gov (United States)

    Sevigny, Leila M; Booth, Brian J; Rowley, Kirk J; Leav, Brett A; Cheslock, Peter S; Garrity, Kerry A; Sloan, Susan E; Thomas, William; Babcock, Gregory J; Wang, Yang

    2013-11-01

    Diphtheria antitoxin (DAT) has been the cornerstone of the treatment of Corynebacterium diphtheriae infection for more than 100 years. Although the global incidence of diphtheria has declined steadily over the last quarter of the 20th century, the disease remains endemic in many parts of the world, and significant outbreaks still occur. DAT is an equine polyclonal antibody that is not commercially available in the United States and is in short supply globally. A safer, more readily available alternative to DAT would be desirable. In the current study, we obtained human monoclonal antibodies (hMAbs) directly from antibody-secreting cells in the circulation of immunized human volunteers. We isolated a panel of diverse hMAbs that recognized diphtheria toxoid, as well as a variety of recombinant protein fragments of diphtheria toxin. Forty-five unique hMAbs were tested for neutralization of diphtheria toxin in in vitro cytotoxicity assays with a 50% effective concentration of 0.65 ng/ml for the lead candidate hMAb, 315C4. In addition, 25 μg of 315C4 completely protected guinea pigs from intoxication in an in vivo lethality model, yielding an estimated relative potency of 64 IU/mg. In comparison, 1.6 IU of DAT was necessary for full protection from morbidity and mortality in this model. We further established that our lead candidate hMAb binds to the receptor-binding domain of diphtheria toxin and physically blocks the toxin from binding to the putative receptor, heparin-binding epidermal growth factor-like growth factor. The discovery of a specific and potent human neutralizing antibody against diphtheria toxin holds promise as a potential therapeutic.

  7. Is sporadic Alzheimer's disease associated with diphtheria toxin?

    Science.gov (United States)

    Merril, Carl R

    2013-01-01

    The two major aspects of Alzheimer's disease (AD) that must be considered in a search for causative agents are its association with aging and its widespread epidemiology. While a number of agents have been identified, additional factors may play a role. An association with diphtheria toxin was suggested by observations that vaccinations may provide protective effects, and the observation that decreased proteins synthesis in cortical regions from AD patients is associated with modification of elongation factor 2, the target of diphtheria toxin. While protection against diphtheria toxin is provided by vaccination, the known decline in the immune system associated with aging would result in a renewed sensitivity to the toxin. An association with diphtheria toxin would be consistent with the observations that the bacteria associated with the toxin, Corynebacterium diphtheria, is often found in the nasopharynx and an early symptom of AD is the loss of smell with a disease progression from the entorhinal cortex to the hippocampus and the neocortical areas. If diphtheria toxin is involved in sporadic AD, booster vaccinations given to elderly individuals might result in a decreased incidence of this disease. As booster DPT vaccinations are already recommended for individuals over 65, cognitive testing at the time of the booster and 5 years later, along with similar cognitive testing in age-matched individuals who decline vaccination, might provide an inexpensive method to investigate whether diphtheria toxin plays a role in AD and the efficacy of DPT booster vaccines for AD.

  8. A case of pharyngeal diphtheria in Germany, June 2015.

    Science.gov (United States)

    Berger, A; Meinel, D M; Schaffer, A; Ziegler, R; Pitteroff, J; Konrad, R; Sing, Andreas

    2016-10-01

    In June 2015, a 45-year-old man suffering from acute necrotic tonsillitis and throat phlegmon was hospitalized in Nuremberg, Germany. After emergency surgery the patient was initially treated with antibiotics. A throat swab grew a toxigenic Corynebacterium diphtheriae biovar mitis strain. The patient's vaccination status was not documented and the patient was tested serologically for anti-diphtheria antibodies showing no protective immunity. Extensive control investigations were performed by the local health department showing no likely source of his infection. No secondary cases were found and the patient completely recovered.

  9. Tetanus, Diphtheria (Td) Vaccine

    Science.gov (United States)

    Decavac® (as a combination product containing Diphtheria, Tetanus Toxoids) ... Tenivac® (as a combination product containing Diphtheria, Tetanus Toxoids) ... Why get vaccinated?Tetanus and diphtheria are very serious diseases. They are rare in the United States today, but people who do become ...

  10. Molecular and Epidemiological Review of Toxigenic Diphtheria Infections in England between 2007 and 2013

    Science.gov (United States)

    Both, Leonard; Collins, Sarah; de Zoysa, Aruni; White, Joanne; Mandal, Sema

    2014-01-01

    Human infections caused by toxigenic corynebacteria occur sporadically across Europe. In this report, we undertook the epidemiological and molecular characterization of all toxigenic corynebacterium strains isolated in England between January 2007 and December 2013. Epidemiological aspects include case demographics, risk factors, clinical presentation, treatment, and outcome. Molecular characterization was performed using multilocus sequence typing (MLST) alongside traditional phenotypic methods. In total, there were 20 cases of toxigenic corynebacteria; 12 (60.0%) were caused by Corynebacterium ulcerans, where animal contact was the predominant risk factor. The remaining eight (40.0%) were caused by Corynebacterium diphtheriae strains; six were biovar mitis, which were associated with recent travel abroad. Adults 45 years and older were particularly affected (55.0%; 11/20), and typical symptoms included sore throat and fever. Respiratory diphtheria with the absence of a pharyngeal membrane was the most common presentation (50.0%; 10/20). None of the eight C. diphtheriae cases were fully immunized. Diphtheria antitoxin was issued in two (9.5%) cases; both survived. Two (9.5%) cases died, one due to a C. diphtheriae infection and one due to C. ulcerans. MLST demonstrated that the majority (87.5%; 7/8) of C. diphtheriae strains represented new sequence types (STs). By adapting several primer sequences, the MLST genes in C. ulcerans were also amplified, thereby providing the basis for extension of the MLST scheme, which is currently restricted to C. diphtheriae. Despite high population immunity, occasional toxigenic corynebacterium strains are identified in England and continued surveillance is required. PMID:25502525

  11. Direct PCR: Alternative Diagnostic Method for Diagnosis of Diphtheria Rapidly, Easily and Cost Effective

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    Sunarno Sunarno

    2013-12-01

    Full Text Available Some diseases require immediate and appropriate treatment to decrease the fatality risk patients incident, for example diphtheria. Time to help patients is very crucial since delay of therapy may increase the mortality cases up to 20 times. In other hands, conventional diagnostic methods (the gold standard for diagnosis of diphtheria is time consuming and laborious. Therefore, an alternative diagnostic method which is rapid, easy and inexpensive is needed. In this case, direct PCR has been proved to reduce time and cost in laboratory examination. This study aimed to develop direct PCR as alternative diagnostic method for diagnosis of diphtheria rapidly, easily, and inexpensive. Fifteen samples include 10 isolates of Corynebacterium diphtheriae (toxigenic and 3 isolates of Corynebacterium non- diphtheriae (nontoxigenic and 2 clinical specimens (throat swab was examined by performing direct PCR method and a standard PCR method was used for optimizing the protocols. Result showed that direct PCR can be used to amplify target genes correctly as well as standard PCR. All of C. diphtheriae samples showed bands at 168 bp (dtxR gene marker and 551 bp (tox gene marker while no band appeared in others. Direct PCR detected at least 71 CFU/uL of bacterial cells in samples. We concluded that direct PCR can be used for alternative diagnostic method for diagnosis of diphtheria which is rapid, easy and cost effective.

  12. Recent Outbreaks of Diphtheria in Dibrugarh District, Assam, India

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    Patgiri, Saurav Jyoti; Saikia, Lahari; Paul, Debosmita

    2016-01-01

    Diphtheria is still a significant child health problem in countries with low immunization coverage. Reports of diphtheria in adult population are also increasing. Here we describe three recent outbreaks of diphtheria in Dibrugarh district, Assam in two consecutive years. The study was undertaken in Assam Medical College & Hospital, Dibrugarh after the diagnosis of two Diphtheria cases in the month of September and October 2015 and another in January 2016. Outbreak investigation was done after defining operational definition and throat swabs were collected from thirty three (33) individuals including three (3) index cases and thirty (30) close contacts. Diagnosis was done by clinical findings, direct microscopy, bacteriological culture and in-house designed multiplex Polymerase Chain Reaction (PCR) of the isolates for the expression of Corynebacterium diphtheriae specific rpoB gene and tox gene. Out of the 10 confirmed cases, 2 and 7 were in the first two outbreaks while only one in the third outbreak respectively. All the cases were of age > 10 years, unimmunized or partially immunized. The overall mortality was 20%. PCR results revealed all the culture positive isolates to be tox gene positive. Diphtheria is a resurgent problem in our region with a significant age shift towards adult. PMID:27630847

  13. Diphtheria outbreak in Maranhão, Brazil: microbiological, clinical and epidemiological aspects.

    Science.gov (United States)

    Santos, L S; Sant'anna, L O; Ramos, J N; Ladeira, E M; Stavracakis-Peixoto, R; Borges, L L G; Santos, C S; Napoleão, F; Camello, T C F; Pereira, G A; Hirata, R; Vieira, V V; Cosme, L M S S; Sabbadini, P S; Mattos-Guaraldi, A L

    2015-03-01

    We describe microbiological, clinical and epidemiological aspects of a diphtheria outbreak that occurred in Maranhão, Brazil. The majority of the 27 confirmed cases occurred in partially (n = 16) or completely (n = 10) immunized children (n = 26). Clinical signs and characteristic symptoms of diphtheria such as cervical lymphadenopathy and pseudomembrane formation were absent in 48% and 7% of the cases, respectively. Complications such as paralysis of lower limbs were observed. Three cases resulted in death, two of them in completely immunized children. Microbiological analysis identified the isolates as Corynebacterium diphtheriae biovar intermedius with a predominant PFGE type. Most of them were toxigenic and some showed a decrease in penicillin G susceptibility. In conclusion, diphtheria remains endemic in Brazil. Health professionals need to be aware of the possibility of atypical cases of C. diphtheriae infection, including pharyngitis without pseudomembrane formation.

  14. Diphtheria in a 7-year-old child in north-eastern Nigeria - management in a resource-poor setting.

    Science.gov (United States)

    Goni, Baba Waru; Gofama, Mustapha M; Lawan, Gana M; Haruna, Yusuph; Bukar, Bakki; Musa, Kida I

    2014-01-01

    We report a case of a 7-year-old unimmunized child who presented with a 2 week history of nasal quality speech, hoarseness of the voice, regurgitation of feeds, and unstable gait. He had a previous history of fever, severe sore throat and bloody nasal discharge. A throat swab was negative for Corynebacterium diphtheria; however, he had received antibiotics at a primary care clinic prior to presentation. A clinical diagnosis of diphtheria with neurologic complication was made and the child was started on oral erythromycin, nasogastric tube feeding and daily physiotherapy, following which he improved. We did not prescribe diphtheria anti-toxin because of its unavailability.

  15. SINGLE CHAIN VARIABLE FRAGMENTS OF ANTIBODIES AGAINST DIPHTHERIA TOXIN B-SUBUNIT ISOLATED FROM PHAGE DISPLAY HUMAN ANTIBODY LIBRARY

    OpenAIRE

    Oliinyk O. S.; Kaberniuk A. A.; Kolibo D. V.; Komisarenko S. V.

    2014-01-01

    Diphtheria toxin is an exoantigen of Corynebacterium diphtheriae that inhibits protein synthesis and kills sensitive cells. The aim of this study was to obtain human recombinant single-chain variable fragment (scFv) antibodies against receptor-binding B subunit of diphtheria toxin. 12 specific clones were selected after three rounds of a phage display naїve (unimmunized) human antibody library against recombinant B-subunit. scFv DNA inserts from these 12 clones were digested with MvaI, an...

  16. International External Quality Assurance for Laboratory Diagnosis of Diphtheria

    Science.gov (United States)

    Neal, S. E.; Efstratiou, A.

    2009-01-01

    The diphtheria surveillance network (DIPNET) encompassing National Diphtheria Reference Centers from 25 European countries is a Dedicated Surveillance Network recognized by the European Commission. A key DIPNET objective is the quality assessment of microbiological procedures for diphtheria across the European Union and beyond. A detailed questionnaire on the level of reference laboratory services and an external quality assessment (EQA) panel comprising six simulated throat specimens were sent to 34 centers. Twenty-three centers are designated National Diphtheria Reference Centers, with the laboratory in the United Kingdom being the only WHO Collaborating Centre. A variety of screening and identification tests were used, including the cysteinase test (20/34 centers), pyrazinamidase test (17/34 centers), and commercial kits (25/34 centers). The classic Elek test for toxigenicity testing is mostly used (28/34 centers), with variations in serum sources and antitoxin concentrations. Many laboratories reported problems obtaining Elek reagents or media. Only six centers produced acceptable results for all six specimens. Overall, 21% of identification and 13% of toxigenicity reports were unacceptable. Many centers could not isolate the target organism, and most found difficulties with the specimens that contained Corynebacterium striatum as a commensal contaminant. Nineteen centers generated either false-positive or negative toxigenic results, which may have caused inappropriate medical management. The discrepancies in this diphtheria diagnostics EQA alarmingly reflect the urgent need to improve laboratory performance in diphtheria diagnostics in Europe, standardize feasible and robust microbiological methods, and build awareness among public health authorities. Therefore, DIPNET recommends that regular workshops and EQA distributions for diphtheria diagnostics should be supported and maintained. PMID:19828749

  17. Corynebacterium endocarditis species-specific risk factors and outcomes

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    Pak Janet B

    2007-02-01

    Full Text Available Abstract Background Corynebacterium species are recognized as uncommon agents of endocarditis, but little is known regarding species-specific risk factors and outcomes in Corynebacterium endocarditis. Methods Case report and Medline search of English language journals for cases of Corynebacterium endocarditis. Inclusion criteria required that cases be identified as endocarditis, having persistent Corynebacterium bacteremia, murmurs described by the authors as identifying the affected valve, or vegetations found by echocardiography or in surgical or autopsy specimens. Cases also required patient-specific information on risk factors and outcomes (age, gender, prior prosthetic valve, other prior nosocomial risk factors (infected valve, involvement of native versus prosthetic valve, need for valve replacement, and death to be included in the analysis. Publications of Corynebacterium endocarditis which reported aggregate data were excluded. Univariate analysis was conducted with chi-square and t-tests, as appropriate, with p = 0.05 considered significant. Results 129 cases of Corynebacterium endocarditis involving nine species met inclusion criteria. Corynebacterium endocarditis typically infects the left heart of adult males and nearly one third of patients have underlying valvular disease. One quarter of patients required valve replacement and one half of patients died. Toxigenic C. diphtheriae is associated with pediatric infections (p C. amycolatum has a predilection for women (p = 0.024, while C. pseudodiphtheriticum infections are most frequent in men (p = 0.023. C. striatum, C. jeikeium and C. hemolyticum are associated with nosocomial risk factors (p C. pseudodiphtheriticum is associated with a previous prosthetic valve replacement (p = 0.004. C. jeikeium infections are more likely to require valve replacement (p = 0.026. Infections involving toxigenic C. diphtheriae and C. pseudodiphtheriticum are associated with decreased survival (p = 0

  18. Differential diagnosis diphtheria adults

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    Yu. I. Liashenko

    2010-01-01

    Full Text Available A total of 1,824 human cases of diphtheria, treated at the Clinical Infectious Diseases Hospital SP Botkin (St. Petersburg during 1993, as well as 19 deaths in 1994. It is known that early diagnosis of infectious diseases, especially diphtheria, contributes to the favorable outcome of the disease. The diagnosis of diphtheria at the prehospital stage is always difficult. Presented in detail the differential diagnosis of the disease, clinically similar to diphtheria: Lacunal angina, angina Simanovsky, infectious mononucleosis, angina Ludwig’s angina Dugue, syphilis, non-infectious with clinical «masks» of diphtheria and other. Diphtheria epidemic of 1993–1994 in Russia and, in particular, in St. Petersburg, showed that the late admission of patients with diphtheria infection in hospitals, usually associated with irregular differential diagnosis of this dangerous disease.

  19. Travelers' Health: Diphtheria

    Science.gov (United States)

    ... Haiti and the Dominican Republic; large outbreaks in Indonesia, Thailand, and Laos have occurred since 2011. CLINICAL ... Diagnosis is confirmed by isolating C. diphtheriae from culture of nasal or throat swabs or membrane tissue. ...

  20. Diphtheria remains a threat to health in the developing world: an overview

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    Ana Luíza Mattos-Guaraldi

    2003-12-01

    Full Text Available Changes in the epidemiology of diphtheria are occurring worldwide. A large proportion of adults in many industrialized and developing countries are now susceptible to diphtheria. Vaccine-induced immunity wanes over time unless periodic booster is given or exposure to toxigenic Corynebacterium diphtheriae occurs. Immunity gap in adults coupled with large numbers of susceptible children creates the potential for new extensive epidemics. Epidemic emergencies may not be long in coming in countries experiencing rapid industrialization or undergoing sociopolitical instability where many of the factors thought to be important in producing epidemic such as mass population movements and difficult hygienic and economic conditions are present. The continuous circulation of toxigenic C. diphtheriae emphasizes the need to be aware of epidemiological features, clinical signs, and symptoms of diphtheria in vaccine era so that cases can be promptly diagnosed and treated, and further public health measures can be taken to contain this serious disease. This overview focused on worldwide data obtained from diphtheria with particular emphasis to main factors leading to recent epidemics, new clinical forms of C. diphtheriae infections, expression of virulence factors, other than toxin production, control strategies, and laboratory diagnosis procedures.

  1. Toxigenic cutaneous diphtheria in a returned traveller.

    Science.gov (United States)

    Abdul Rahim, Nur R; Koehler, Ann P; Shaw, Doug D; Graham, Caitlin R

    2014-12-31

    Diphtheria is rarely reported in Australia. A case of cutaneous diphtheria was reported to the South Australian Department for Health and Ageing in April 2013 in an Australian-born 18-year-old female following travel in India. The case presented with a skin ulcer on her toe. Toxigenic Corynebacterium diphtheriae was isolated from a swab of the lesion. The case was treated with antibiotics. The public health response included infection control advice, assessing the case and household contacts for organism carriage and providing antimicrobial chemoprophylaxis to contacts. Although cutaneous diphtheria is not included as part of the Australian communicable disease surveillance case definition, this may be an oversight as international evidence demonstrates that it is a source of organism transmission and can potentially result in outbreaks among susceptible populations. This formed the rationale for the public health response to this particular case. The protocol for the public health management of diphtheria in South Australia has since been revised to include cutaneous lesions caused by the toxigenic strain of the organism as part of the surveillance case definition. This work is copyright. You may download, display, print and reproduce the whole or part of this work in unaltered form for your own personal use or, if you are part of an organisation, for internal use within your organisation, but only if you or your organisation do not use the reproduction for any commercial purpose and retain this copyright notice and all disclaimer notices as part of that reproduction. Apart from rights to use as permitted by the Copyright Act 1968 or allowed by this copyright notice, all other rights are reserved and you are not allowed to reproduce the whole or any part of this work in any way (electronic or otherwise) without first being given the specific written permission from the Commonwealth to do so. Requests and inquiries concerning reproduction and rights are to be sent

  2. Resurgence of diphtheria in rural areas of North Karnataka, India

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    Mahantesh V Parande

    2017-01-01

    Full Text Available Background: A diphtheria outbreak was identified from Vijayapura (formerly Bijapur district in the South Indian state of Karnataka in 2011. There was a surge in the number of throat swab samples received under the Integrated Disease Surveillance Programme (IDSP in North Karnataka since then. Objectives: A microbiological study was undertaken to generate information on the status of resurgence of the disease in the region. Materials and Methods: Throat swabs from 432 suspected cases of diphtheria during 2012–2015 were obtained from government hospitals and primary health centres of 8 districts in North Karnataka and were processed for the culture and identification of Corynebacterium diphtheriae. Polymerase chain reaction for the presence of toxin gene (toxA and toxB was carried out on the isolates. Antibiotic sensitivity tests were performed on the isolates with a panel of 14 antibiotics. Results: Thirty-eight (8.79% out of 432 samples yielded C. diphtheriae on culture. All isolates possessed the diphtheria toxin gene. Out of the 38 confirmed cases, whereas 21 (55.26% were between 1 and 5 years of age, 14 (36.84% were aged between 5 and 10 years. Male children were three times more than females in confirmed cases. No information was available on the immunisation status of the cases. Emergence of resistance to penicillin was found with minimum inhibitory concentration reaching up to 6.00 μg/ml. Conclusion and Discussion: Our study identified an upsurge in cases of diphtheria in North Karnataka, particularly in Vijayapura District, and to the best of our knowledge, reports the emergence of penicillin resistance for the first time in India. The study calls for enhanced surveillance for the disease, making antidiphtheritic serum available in key hospitals in the region and serves to provide a baseline for future assessment of the impact of the recently launched 'Mission Indradhanush' programme in strengthening Universal Immunisation Programme

  3. Public health action following an outbreak of toxigenic cutaneous diphtheria in an Auckland refugee resettlement centre.

    Science.gov (United States)

    Reynolds, Gary E; Saunders, Helen; Matson, Angela; O'Kane, Fiona; Roberts, Sally A; Singh, Salvin K; Voss, Lesley M; Kiedrzynski, Tomasz

    2016-12-24

    Global forced displacement has climbed to unprecedented levels due largely to regional conflict. Degraded public health services leave displaced people vulnerable to multiple environmental and infectious hazards including vaccine preventable disease. While diphtheria is rarely notified in New Zealand, a 2 person outbreak of cutaneous diphtheria occurred in refugees from Afghanistan in February 2015 at the refugee resettlement centre in Auckland. Both cases had uncertain immunisation status. The index case presented with a scalp lesion during routine health screen and toxigenic Corynebacterium diphtheriae was isolated. A secondary case of cutaneous diphtheria and an asymptomatic carrier were identified from skin and throat swabs. The 2 cases and 1 carrier were placed in consented restriction until antibiotic treatment and 2 clearance swabs were available. A total of 164 contacts were identified from within the same hostel accommodation as well as staff working in the refugee centre. All high risk contacts (n=101) were swabbed (throat, nasopharynx and open skin lesions) to assess C. diphtheriae carriage status. Chemoprophylaxis was administered (1 dose of intramuscular benzathine penicillin or 10 days of oral erythromycin) and diphtheria toxoid-containing vaccine offered regardless of immunisation status. Suspected cases were restricted on daily monitoring until swab clearance. A group of 49 low risk contacts were also offered vaccination. Results suggest a significant public health effort was required for a disease rarely seen in New Zealand. In light of increased worldwide forced displacement, similar outbreaks could occur and require a rigorous public health framework for management.

  4. Multiplex polymerase chain reaction to identify and determine the toxigenicity of Corynebacterium spp with zoonotic potential and an overview of human and animal infections

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    Luciene de Fatima Costa Torres

    2013-05-01

    Full Text Available Corynebacterium diphtheriae, Corynebacterium ulcerans and Corynebacterium pseudotuberculosis constitute a group of potentially toxigenic microorganisms that are related to different infectious processes in animal and human hosts. Currently, there is a lack of information on the prevalence of disease caused by these pathogens, which is partially due to a reduction in the frequency of routine laboratory testing. In this study, a multiplex polymerase chain reaction (mPCR assay that can simultaneously identify and determine the toxigenicity of these corynebacterial species with zoonotic potential was developed. This assay uses five primer pairs targeting the following genes: rpoB (Corynebacterium spp, 16S rRNA (C. ulcerans and C. pseudotuberculosis, pld (C. pseudotuberculosis, dtxR (C. diphtheriae and tox [diphtheria toxin (DT ]. In addition to describing this assay, we review the literature regarding the diseases caused by these pathogens. Of the 213 coryneform strains tested, the mPCR results for all toxigenic and non-toxigenic strains of C . diphtheriae, C. ulcerans and C. pseudotuberculosis were in 100% agreement with the results of standard biochemical tests and PCR-DT. As an alternative to conventional methods, due to its advantages of specificity and speed, the mPCR assay used in this study may successfully be applied for the diagnosis of human and/or animal diseases caused by potentially toxigenic corynebacterial species.

  5. Diphtheria, Tetanus, Pertussis: Ask the Experts

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    ... Tetanus, Pertussis Ask the Experts: Diseases & Vaccines Diphtheria, Tetanus, Pertussis Ask the Experts Home Combination Vaccines Diphtheria ... have died. How many doses of pediatric diphtheria-tetanus-acellular pertussis (DTaP) vaccine does an infant need ...

  6. DIPHTHERIA IN A VACCINATED ADULT IN RIO DE JANEIRO, BRAZIL Difteria em adulto vacinado no Rio de Janeiro, Brasil

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    Ana Luiza Mattos-Guaraldi

    2001-10-01

    Full Text Available In 1999, a case of diphtheria in a 32-year-old woman was reported. The patient developed a sore throat immediately after participating of a five-day meeting with European workers in Rio de Janeiro. Her history included complete pediatric immunization (DTP and three doses of adult formulation tetanus and diphtheria toxoid (dT two years earlier. Clinical diagnosis of diphtheria was not made until microbiologic examination of specimens confirmed toxigenicity of Corynebacterium diphtheriae var. gravis, a biotype currently found circulating within Europe where diphtheria remains epidemic. This case reinforces the potential susceptibility of Brazilian adults to epidemic diphtheria in the vaccine era.Um caso de difteria ocorreu, em 1999, em mulher de 32 anos de idade. A paciente iniciou episódio de dor de garganta imediatamente após participação em reunião com profissionais europeus durante cinco dias consecutivos, no Rio de Janeiro. Ela declarou ter sido submetida ao esquema completo de imunização contra difteria (DTP-tríplice bacteriana na infância e a doses de reforço (dT-dupla adulto há dois anos. O diagnóstico clínico da doença só foi firmado após o laboratório de microbiologia ter confirmado a capacidade de produção de toxina pela amostra isolada de Corynebacterium diphtheriae var. gravis, biotipo não fermentador de sacarose comumente encontrado em diversos países europeus e responsável pela atual epidemia na região correspondente a antiga União Soviética. Na era da vacinação antidiftérica, indivíduos adultos de nossa comunidade podem apresentar-se potencialmente susceptíveis a difteria.

  7. [Serum sickness in diphtheria].

    Science.gov (United States)

    Vozianova, Zh I; Chepilko, K I

    1999-01-01

    As many as 2247 patients with different clinical forms of diphtheria were examined. Antidiphtheric serum (ADS) was administered in 1556 children, the dosage being determined by condition of the patient. Serum sickness developed at day 7 to 9 in 24 (1.5%); 10 patients were found to run a mild course, 14--moderately severe. 6 patients had allergic reactions: 3--to antibiotic (penicillin), urticaria type, 1--to pertussoid-tetanic anatoxin, 2 had pollinosis-type reaction. Thus, serum sickness has practical value, which fact requires a detailed allergic history together with skin tests to be performed before the administration of ADS.

  8. Diphtheria: It is still prevalent!!!

    Science.gov (United States)

    Jain, Avani; Samdani, Sunil; Meena, Vinod; Sharma, Man Prakash

    2016-07-01

    Diphtheria is a respiratory infectious disease of childhood. It is a fatal disease and may cause complications if not recognized early and treated properly. Despite availability of effective vaccination it continues to be reported from many parts of the world particularly developing countries. To assess the demographic and clinical characteristics of diphtheria patients, and the predictors of outcomes of respiratory diphtheria. A prospective analysis of 180 patients with a clinical diagnosis of respiratory diphtheria admitted from 2011 to 2014 at a tertiary referral hospital. They were evaluated with respect to demographic details, immunization status, clinical features, complications and outcomes. Most common age group affected was children less than 5 years of age (87 cases, 48.33%). The peak incidence of diphtheria was seen in the months of September and October (111 cases, 62%). Majority of the patients were unimmunized (54%), followed by partially immunized (21%). The most common complication was respiratory in 80 cases (44%), followed by cardiac complications in 54 cases (30%), and renal (16%) and neurological complications (10%). Cardiac complications were associated with the highest mortality rate (63%). The presence of bull neck and pseudomembrane score >2 was associated with a high mortality. Diphtheria is still a preventable public health problem in many developing countries. Improved vaccination coverage, including booster dosage, coupled with early detection and effective treatment, may all reduce incidence and mortality. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Adjuvants for Clostridium tetani and Clostridium diphtheriae vaccines updating.

    Science.gov (United States)

    Alshanqiti, Fatimah M; Al-Masaudi, Saad B; Al-Hejin, Ahmed M; Redwan, Elrashdy M

    2017-01-01

    It's known that diphtheria and tetanus are a contagious lethal diseases over the years, they caused by pathogenic microbes corynebacterium diphtheria and Clostridium tetani, respectively. The diseases result from the production of bacterial toxin. Vaccination with bacterial toxoid vaccines adsorbed on particulates adjuvants still are the best way to prevent this epidemic diseases from spread. The particulate vaccines have been shown to be more efficient than soluble one for the induction of the immune responses. Nanoparticles can be engineered to enhance the immune responses. As well known the immune response to inactivate killed and subunit vaccine enhances by alum adjuvants. The adjuvants examined and tested after reducing its size to particle size, thus mimic size of viruses which is considered smallest units can derive the immune system. The major issue is minimizing the adjuvant particles, to gain insight of resulting immunity types and impact on immune response. The adjuvant effect of micro/nanoparticles appears to largely be a consequence of their uptake into antigen presenting cells.

  10. Comparison of four serological methods for the detection of diphtheria anti-toxin antibody.

    Science.gov (United States)

    Walory, J; Grzesiowski, P; Hryniewicz, W

    2000-11-01

    The aim of this study was to compare four serological methods for the detection of Corynebacterium diphtheriae IgG anti-toxin antibodies (IgG-DTAb) in human serum. One hundred serum samples were evaluated for C. diphtheriae IgG-DTAb by four different methods: passive haemagglutination (PHA), latex agglutination test (LA), toxoid enzyme-linked immunosorbent assay (Toxoid-ELISA), and toxin-binding inhibition enzyme-linked immunosorbent assay (ToBI-ELISA). As the external standardisation the neutralisation test for C. diphtheriae toxin in Vero cells (TN Vero) was used. For internal standardisation of IgG-DTAb titres, the WHO standard serum of human diphtheria antitoxin was used. The study revealed a poor correlation between the reference test and the PHA (r=0.34 Pearson's correlation coefficient), an acceptable correlation for the LA (r=0.74), a good correlation for the Toxoid-ELISA (r=0.81) and a very good correlation for ToBI-ELISA (r=0.93). The sensitivity measurements of PHA, LA, Toxoid-ELISA and ToBI-ELISA tests, were 14, 100, 94, 96% respectively and the corresponding specificity characteristics were 86, 76, 94, 90 respectively. Of the four evaluated methods, the ToBI-ELISA could be recommended for scientific and precise laboratory assays of diphtheria antibody levels in humans. For screening purposes the Toxoid-ELISA could be used, but the accuracy of antibody titres below 0.1 IU/ml, considered as the limits of protection, is questionable. Both tests offer very useful alternatives to the in vitro diphtheria toxin neutralisation test in Vero cells. Because of their unsatisfactory correlation and sensitivity as compared to the reference method, PHA and LA should be avoided and replaced by one of the two enzyme immunoassays.

  11. Concurrent diphtheria and infectious mononucleosis: difficulties for management, investigation and control of diphtheria in developing countries.

    Science.gov (United States)

    Mattos-Guaraldi, A L; Damasco, P V; Gomes, D L R; Melendez, M G; Santos, L S; Marinelli, R S; Napoleão, F; Sabbadini, P S; Santos, C S; Moreira, L O; Hirata, R

    2011-11-01

    We report a case of concurrent diphtheria and infectious mononucleosis in an 11-year-old Brazilian child. Two days after specific treatment for diphtheria was started the patient was discharged following clinical recovery. This case highlights the difficulties in the clinical diagnosis of diphtheria in partially immunized individuals, and for the management and control of diphtheria in developing countries.

  12. Tdap (tetanus, diphtheria, pertussis) Vaccine and Pregnancy

    Science.gov (United States)

    Tetanus, Diphtheria and Pertussis (Tdap) Vaccine In every pregnancy, a woman starts out with a 3-5% ... This sheet talks about whether exposure to the tetanus, diphtheria, and pertussis (or Tdap) vaccine may increase ...

  13. Tdap (tetanus, diphtheria, pertussis) Vaccine and Pregnancy

    Science.gov (United States)

    Tetanus, Diphtheria and Pertussis (Tdap) Vaccine In every pregnancy, a woman starts out with a 3-5% ... This sheet talks about whether exposure to the tetanus, diphtheria, and pertussis (or Tdap) vaccine may increase ...

  14. [Treating diphtheria in the 21st century].

    Science.gov (United States)

    Beneš, J; Džupová, O

    2013-12-01

    The existing recommendations for treatment of diphtheria involve the use of a hyperimmune serum neutralizing diphtheria toxin and subsequent penicillin therapy killing the pathogen. Unfortunately, diphtheria antitoxin is no longer available in the Czech Republic and this condition seems to remain permanent. Thus, the whole strategy for diphtheria treatment must be changed. Instead of penicillin, antibiotics inhibiting bacterial protein synthesis such as clindamycin or linezolid should be administered. Macrolides could be appropriate in mild to moderate disease.

  15. SINGLE CHAIN VARIABLE FRAGMENTS OF ANTIBODIES AGAINST DIPHTHERIA TOXIN B-SUBUNIT ISOLATED FROM PHAGE DISPLAY HUMAN ANTIBODY LIBRARY

    Directory of Open Access Journals (Sweden)

    Oliinyk O. S.

    2014-02-01

    Full Text Available Diphtheria toxin is an exoantigen of Corynebacterium diphtheriae that inhibits protein synthesis and kills sensitive cells. The aim of this study was to obtain human recombinant single-chain variable fragment (scFv antibodies against receptor-binding B subunit of diphtheria toxin. 12 specific clones were selected after three rounds of a phage display naїve (unimmunized human antibody library against recombinant B-subunit. scFv DNA inserts from these 12 clones were digested with MvaI, and 6 unique restriction patterns were found. Single-chain antibodies were expressed in Escherichia coli XL1-blue. The recombinant proteins were characterized by immunoblotting of bacterial extracts and detection with an anti-E-tag antibody. The toxin B-subunit-binding function of the single-chain antibody was shown by ELISA. The affinity constants for different clones were found to be from 106 to 108 М–1. Due to the fact, that these antibody fragments recognized epitopes in the receptor-binding Bsubunit of diphtheria toxin, further studies are interesting to evaluate their toxin neutralization properties and potential for therapeutic applications. Obtained scFv-antibodies can also be used for detection and investigation of biological properties of diphtheria toxin.

  16. Immunity to Diphtheria in Haemodialysis Patients

    OpenAIRE

    Abdolreza S. Jahromi; Mortaza Pourahmd; Sara Azhdari; Gita Manshoori; Abdolhossain Madani; Seyed H. Moosavy

    2011-01-01

    Problem statement: The incidence of infectious diseases is increased in patients with chronic renal failure. Chronic renal failure severely influences the immune functions of the host. Diphtheria is of great epidemiological concern. Although mainly observed during childhood, unvaccinated adults and relatively immunocompromised patients are at increased risk for acquiring diphtheria. Approach: To evaluate the anti-Diphtheria immunity level in southern Iranian patients ...

  17. Comparison of a Multiplex Flow Cytometric Assay with Enzyme-Linked Immunosorbent Assay for Quantitation of Antibodies to Tetanus, Diphtheria, and Haemophilus influenzae Type b

    OpenAIRE

    Pickering, Jerry W.; Martins, Thomas B.; Schroder, M. Carl; Hill, Harry R.

    2002-01-01

    We developed a multiplexed indirect immunofluorescence assay for antibodies to Haemophilus influenza type b (Hib) polysaccharide and the toxoids of Clostridium tetani (Tet) and Corynebacterium diphtheriae (Dip) based on the Luminex multiple-analyte profiling system. A pooled serum standard was calibrated against World Health Organization standards for Dip and Tet and an international standard for Hib. The multiplexed Luminex assay was compared to individual enzyme-linked immunosorbent assays ...

  18. Diphtheria rare localization in adults

    Directory of Open Access Journals (Sweden)

    Yu. I. Liashenko

    2011-01-01

    Full Text Available Last 25 years in the country established sporadic diphtheria morbidity (less than 0.1 per 100 000 people. In this situation, the attention of medical specialists pre-hospital and hospital health care system is reduced, especially for diseases with a rare localization of pathological process. Mentioned circumstances contribute to delayed diagnosis and treatment of his patients, the major cause of complicated infection, often its unfavorable outcome and a factor of the epidemic of trouble for the infection. The authors present material evidence that the rare forms of diphtheria in the period of sporadic disease in much the same as in the epidemic, and describe the clinical manifestations and course of diphtheria of the nose, eyes, throat, genitals, mouth and gastrointestinal tract in modern conditions.

  19. Potency of a human monoclonal antibody to diphtheria toxin relative to equine diphtheria anti-toxin in a guinea pig intoxication model.

    Science.gov (United States)

    Smith, Heidi L; Cheslock, Peter; Leney, Mark; Barton, Bruce; Molrine, Deborah C

    2016-08-17

    Prompt administration of anti-toxin reduces mortality following Corynebacterium diphtheriae infection. Current treatment relies upon equine diphtheria anti-toxin (DAT), with a 10% risk of serum sickness and rarely anaphylaxis. The global DAT supply is extremely limited; most manufacturers have ceased production. S315 is a neutralizing human IgG1 monoclonal antibody to diphtheria toxin that may provide a safe and effective alternative to equine DAT and address critical supply issues. To guide dose selection for IND-enabling pharmacology and toxicology studies, we dose-ranged S315 and DAT in a guinea pig model of diphtheria intoxication based on the NIH Minimum Requirements potency assay. Animals received a single injection of antibody premixed with toxin, were monitored for 30 days, and assigned a numeric score for clinical signs of disease. Animals receiving ≥ 27.5 µg of S315 or ≥ 1.75 IU of DAT survived whereas animals receiving ≤ 22.5 µg of S315 or ≤ 1.25 IU of DAT died, yielding a potency estimate of 17 µg S315/IU DAT (95% CI 16-21) for an endpoint of survival. Because some surviving animals exhibited transient limb weakness, likely a systemic sign of toxicity, DAT and S315 doses required to prevent hind limb paralysis were also determined, yielding a relative potency of 48 µg/IU (95% CI 38-59) for this alternate endpoint. To support advancement of S315 into clinical trials, potency estimates will be used to evaluate the efficacy of S315 versus DAT in an animal model with antibody administration after toxin exposure, more closely modeling anti-toxin therapy in humans.

  20. Characterization of C-S Lyase from C. diphtheriae: A Possible Target for New Antimicrobial Drugs

    Directory of Open Access Journals (Sweden)

    Alessandra Astegno

    2013-01-01

    Full Text Available The emergence of antibiotic resistance in microbial pathogens requires the identification of new antibacterial drugs. The biosynthesis of methionine is an attractive target because of its central importance in cellular metabolism. Moreover, most of the steps in methionine biosynthesis pathway are absent in mammals, lowering the probability of unwanted side effects. Herein, detailed biochemical characterization of one enzyme required for methionine biosynthesis, a pyridoxal-5′-phosphate (PLP- dependent C-S lyase from Corynebacterium diphtheriae, a pathogenic bacterium that causes diphtheria, has been performed. We overexpressed the protein in E. coli and analyzed substrate specificity, pH dependence of steady state kinetic parameters, and ligand-induced spectral transitions of the protein. Structural comparison of the enzyme with cystalysin from Treponema denticola indicates a similarity in overall folding. We used site-directed mutagenesis to highlight the importance of active site residues Tyr55, Tyr114, and Arg351, analyzing the effects of amino acid replacement on catalytic properties of enzyme. Better understanding of the active site of C. diphtheriae C-S lyase and the determinants of substrate and reaction specificity from this work will facilitate the design of novel inhibitors as antibacterial therapeutics.

  1. Diphtheria, Tetanus, and Pertussis (DTaP) Vaccine

    Science.gov (United States)

    Certiva® (as a combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis Vaccine) ... Daptacel® (as a combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis Vaccine)

  2. More than 20 years after re-emerging in the 1990s, diphtheria remains a public health problem in Latvia.

    Science.gov (United States)

    Kantsone, Ieva; Lucenko, Irina; Perevoscikovs, Jurijs

    2016-12-01

    In 1994, the World Health Organization (WHO) declared the goal of eliminating diphtheria within the WHO European Region by the year 2000. However, in 1990 an epidemic emerged within the Russian Federation and spread to other countries, including Latvia, by 1994. We describe national surveillance and immunisation coverage data in Latvia from 1994 to 2014 and present historical data from 1946. We defined a laboratory-confirmed case as a clinical case in which toxin-producing Corynebacterium diphtheriae, C. ulcerans or C. pseudotuberculosis was isolated. From 1994 to 2014, 1,515 cases were reported, giving an average annual incidence of 3.2 cases per 100,000 inhabitants (range 0.1-14.8), with the highest incidence in age groups 5-19 and 40-49 years (4.4 and 4.3/100,000, respectively); 111 deaths were reported, 83.8% cases were laboratory-confirmed. Most cases occurred in unvaccinated adults. To improve disease control a supplementary immunisation campaign for adults was initiated in 1995, and by the end of 1998 national coverage among adults reached 70%, and reached 77% in 2003, but declined to 59% by 2014. Diphtheria remains a problem in Latvia with continued circulation of toxin-producing strains of C. diphtheriae. We recommend to strengthen immunisation to cover adults, as well as the education of health professionals and a serological survey. This article is copyright of The Authors, 2016.

  3. Diphtheria outbreak in Norway: lessons learned.

    Science.gov (United States)

    Rasmussen, Inge; Wallace, Sean; Mengshoel, Anne Torunn; Høiby, E Arne; Brandtzæg, Petter

    2011-12-01

    We describe an outbreak of diphtheria in Norway that occurred in 2008 and affected 3 unvaccinated family members. The epidemic caught the public health system off-guard on most levels; the diagnosis was distrusted due to its rarity, no diphtheria anti-toxin was available, and notification procedures were not rigorously followed.

  4. Expression and purification of truncated diphtheria toxin, DT386, in Escherichia coli: An attempt for production of a new vaccine against diphtheria

    Science.gov (United States)

    Shafiee, Fatemeh; Rabbani, Mohammad; Behdani, Mahdi; Jahanian-Najafabadi, Ali

    2016-01-01

    The aim of this study was to produce a recombinant protein consisting of the catalytic and translocation domains of diphtheria toxin for its later application as a vaccine candidate against Corynebacterium diphtheria. To achieve this goal, at first, the amino acid sequence of DT386 was used for prediction of T and B cell epitopes using on-line servers. The DT386 coding sequence was synthesized and subcloned into the NcoI and XhoI sites of pET28a plasmid and recombinant pET28a plasmid was used to transform Escherichia coli BL21 (DE3) host cells. Afterwards, recombinant cells were selected and subjected to induction of expression by 1 mM isopropyl β-D-1-thiogalactopyranoside, (IPTG). Expression of the desired protein was evaluated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting, and finally, the recombinant protein was purified using nickel affinity chromatography. The results of epitope prediction using on-line servers established the ability of DT386 for stimulation of immune system against diphtheria toxin. Restriction digestion of the recombinant plasmids using NcoI and XhoI enzymes confirmed the fidelity of cloning by producing a band of about 1200 bp. SDS-PAGE analysis following induction of expression and also purification step confirmed the expression of the desired protein by showing a band of about 45 kDa. In addition, Western blot analysis using anti-6X-His antibody confirmed the identity of the expected protein. In conclusion, in the present study we amplified and cloned the coding sequence of DT386 fragment, followed by its expression by E. coli BL21 (DE3) cells. Then, the expressed protein was purified and will be used for later studies of evaluation of its immunogenic properties. PMID:27920826

  5. Toxigenic Corynebacterium ulcerans isolated from a wild bird (ural owl) and its feed (shrew-moles): comparison of molecular types with human isolates.

    Science.gov (United States)

    Katsukawa, Chihiro; Umeda, Kaoru; Inamori, Ikuko; Kosono, Yuka; Tanigawa, Tomokazu; Komiya, Takako; Iwaki, Masaaki; Yamamoto, Akihiko; Nakatsu, Susumu

    2016-03-22

    Corynebacterium ulcerans is a pathogen causing diphtheria-like illness to humans. In contrast to diphtheria by Corynebacterium diphtheriae circulating mostly among humans, C. ulcerans infection is zoonotic. The present study aimed to clarify how a zoonotic pathogen C. ulcerans circulates among wild birds and animals. By screening 380 birds, a single strain of toxigenic C. ulcerans was isolated from a carnivorous bird, ural owl (Strix uralensis). The bacterium was also isolated from two individuals of Japanese shrew-mole (Urotrichus talpoides), a food preference of the owl. Analysis by ribotyping showed that the owl and mole isolates were classified in a group, suggesting that C. ulcerans can be transmissible among wild birds and their prey animals. Moreover, our isolates were found to belong to a group of previously reported C. ulcerans isolates from dogs and a cat, which are known to serve as sources for human infection. The findings suggest that the shrew-mole may be a potential reservoir of a zoonotic pathogen C. ulcerans.

  6. Neurologic manifestations of diphtheria and pertussis.

    Science.gov (United States)

    Sanghi, Viraj

    2014-01-01

    Historically, diphtheria was a major cause of morbidity and mortality in the prevaccine era. However, in recent times there has been a resurgence of diphtheria, especially in the newly independent states of the former USSR. Diphtheritic polyneuropathy can be a serious complication in patients who have a severe infection. In patients with pertussis, seizures and encephalopathy can occur as a complication of asphyxia. Vaccination against diphtheria and pertussis in children and booster vaccination in adults is recommended. DTP (diphtheria, tetanus, pertussis) vaccination has been shown to increase the risk of febrile seizures in children. Currently, it appears that the risk of vaccine-induced encephalopathy and/or epilepsy following DTP vaccination, if any, is extremely low. © 2014 Elsevier B.V. All rights reserved.

  7. Booster vaccination against tetanus and diphtheria: insufficient protection against diphtheria in young and elderly adults.

    Science.gov (United States)

    Grasse, Marco; Meryk, Andreas; Schirmer, Michael; Grubeck-Loebenstein, Beatrix; Weinberger, Birgit

    2016-01-01

    We have recently demonstrated that single shot vaccinations against tetanus and diphtheria do not lead to long-lasting immunity against diphtheria in elderly persons despite administration at 5 year intervals. In the present study we have immunized a group of young adults against tetanus and diphtheria to compare the pre- and 28 days post-vaccination immune responses in the young group with results of the same vaccination performed in an elderly group of a previous study. We also studied protection in both groups 5 years after vaccination. We compared antibody titers at all three time points and also analyzed the T cell responses in both age groups 5 years after vaccination. Before vaccination 9 % of the elderly persons were not protected against tetanus, and 48 % did not have protection against diphtheria. In the young group all participants were protected against tetanus, but 52 % were also unprotected against diphtheria before vaccination. 28 days after vaccination 100 % of all participants had protective antibody concentrations against tetanus and only a small percentage in each age group (diphtheria. 5 years later, 100 % of both cohorts were still protected against tetanus, but 24 % of the young and 54 % of the elderly group were unprotected against diphtheria. Antibody concentrations against diphtheria measured by ELISA correlated well with their neutralizing capacity. T cell responses to tetanus and diphtheria did not differ between young and old persons. We conclude that booster vaccinations against tetanus and diphtheria according to present recommendations provide long-lasting protection only against tetanus, but not against diphtheria, independently of age. In elderly persons, the level of protection is even lower, probably due to intrinsic age-related changes within the immune system and/or insufficient vaccination earlier in life.

  8. Native Valve Endocarditis due to Corynebacterium striatum confirmed by 16S Ribosomal RNA Sequencing: A Case Report and Literature Review

    Science.gov (United States)

    2016-01-01

    Corynebacterium species are non-fermentous Gram-positive bacilli that are normal flora of human skin and mucous membranes and are commonly isolated in clinical specimens. Non-diphtheriae Corynebacterium are regarded as contaminants when found in blood culture. Currently, Corynebacterium striatum is considered one of the emerging nosocomial agents implicated in endocarditis and serious infections. We report a case of native-valve infective endocarditis caused by C. striatum, which was misidentified by automated identification system but identified accurately by 16S ribosomal RNA sequencing, in a 55-year-old male patient. The patient had two mobile vegetations on his mitral valve, both of which had high embolic risk. Through surgical valve replacement and an antibiotic regimen, the patient recovered completely. In unusual clinical scenarios, C. striatum should not be simply dismissed as a contaminant when isolated from clinical specimens. The possibility of C. striatum infection should be considered even in an immunocompetent patient, and we suggest a genotypic assay, such as 16S rRNA sequencing, to confirm species identity. PMID:27659439

  9. Mechanism of Metal Ion Activation of the Diphtheria Toxin Repressor DtxR

    Energy Technology Data Exchange (ETDEWEB)

    D' Aquino,J.; Tetenbaum-Novatt, J.; White, A.; Berkovitch, F.; Ringe, D.

    2005-01-01

    The diphtheria toxin repressor (DtxR) is a metal ion-activated transcriptional regulator that has been linked to the virulence of Corynebacterium diphtheriae. Structure determination has shown that there are two metal ion binding sites per repressor monomer, and site-directed mutagenesis has demonstrated that binding site 2 (primary) is essential for recognition of the target DNA repressor, leaving the role of binding site 1 (ancillary) unclear. Calorimetric techniques have demonstrated that although binding site 1 (ancillary) has high affinity for metal ion with a binding constant of 2 x 10{sup -7}, binding site 2 (primary) is a low-affinity binding site with a binding constant of 6.3 x 10{sup -4}. These two binding sites act in an independent fashion, and their contribution can be easily dissected by traditional mutational analysis. Our results clearly demonstrate that binding site 1 (ancillary) is the first one to be occupied during metal ion activation, playing a critical role in stabilization of the repressor. In addition, structural data obtained for the mutants Ni-DtxR(H79A, C102D), reported here, and the previously reported DtxR(H79A) have allowed us to propose a mechanism of metal activation for DtxR.

  10. 广东省一例白喉疑似病例的病原学检测和流行病学调查%Etiologic detection and epidemiological analysis of one suspected case of diphtheria in Guangdong province

    Institute of Scientific and Technical Information of China (English)

    刘美真; 张伟铮; 疏俊; 陈经雕; 管大伟; 傅传喜; 杨波; 柯碧霞; 柯昌文

    2011-01-01

    目的 对广东省发现的1例疑似白喉病例进行流行病学调查和病原学检测,以明确诊断。方法 2010年7月6日,广东省广州市大学城某医院在1例鼻咽癌患者的鼻腔分泌物中检出白喉棒状杆菌。对患者及其密切接触者进行流行病学调查,采集患者及其密切接触者咽拭子标本(3份)和患者鼻腔分泌物标本(1份),采用血平板和吕氏斜面进行细菌分离培养,对阳性菌株进行细菌涂片染色鉴定;应用梅里埃API Coryne棒状杆菌生化鉴定卡进行生化鉴定;应用PCR方法测定白喉棒状杆菌β棒状杆菌噬菌体tox基因;应用气相色谱法进行脂肪酸分析;采用白喉棒状杆菌(重型,编号:CMCC 38009)作为阳性对照。结果 患者近1个多月无外出史及来访史,否认疫苗接种史。对患者的家人及5名密切接触者进行调查,未发现有类似症状的病例。从患者鼻腔分泌物中分离到1株白喉棒状杆菌,革兰染色阳性,形态多样化,经吕氏斜面培养后进行革兰染色和奈瑟染色,菌体一端或两端见特征性的异染颗粒,API Coryne生化鉴定提示99.4%是缓和白喉棒状杆菌。用气相色谱法进行脂肪酸分析,结果显示为白喉棒状杆菌。患者及其密切接触者咽拭子均未分离到白喉棒状杆菌。PCR检测白喉棒状杆菌β棒状杆菌噬菌体tox基因,结果为阴性。结论 此次分离到的白喉棒状杆菌菌株不带有毒素生物结构基因,为非毒源菌株,该病例为无毒白喉棒状杆菌健康带菌者。%Objective To clarify the diagnosis of one suspected case of diphtheria in Guangdong province by epidemiological analysis and etiologic detection. Methods On July 6th 2010, the corynebacterium diphtheria was detected from the nasal secretions of one nasopharyngeal carcinoma patient in a college-town hospital in Guangzhou City, Guangdong Province. The patient and the close contacts

  11. STUDY OF CARDIAC INVOLVEMENT IN DIPHTHERIA

    Directory of Open Access Journals (Sweden)

    Bala Raju Gundam

    2016-07-01

    Full Text Available BACKGROUND Diphtheria still endemic in many developing countries and is responsible for high case fatality. Myocardial involvement is a serious complication of diphtheria and diphtheria myocarditis frequently complicated by arrhythmias causes sudden death if not managed properly. So, early and adequate administration of Anti-Diphtheritic Serum (ADS and frequent monitoring particularly 24 hrs. ECG monitoring is helpful to detect any serious cardiac arrhythmias. METHODS A prospective study on patients who were culture positive diagnosed on the basis of WHO definition were treated and analysed in respect to homographic details, immunisation strategy, and clinical features with particular attention to myocarditis. RESULTS In the study, common age group affected by diphtheria was 5 to 10 years. Incidence of myocarditis more in same age group. Out of 64 patients with myocarditis, 23 patients died. CONCLUSION Incidence of diphtheria has increased in the recent years. Commonly effected age group is 5 to 10 years and most of them are presented with asymptomatic myocarditis. Symptomatic diphtheritic myocarditis has high mortality rate even with aggressive management. Patient who presented with either LBBB alone are with combination of other conduction of abnormalities has high mortality rate.

  12. Booster vaccination against tetanus and diphtheria: insufficient protection against diphtheria in young and elderly adults

    OpenAIRE

    Grasse, Marco; Meryk, Andreas; Schirmer, Michael; Grubeck-Loebenstein, Beatrix; Weinberger, Birgit

    2016-01-01

    We have recently demonstrated that single shot vaccinations against tetanus and diphtheria do not lead to long-lasting immunity against diphtheria in elderly persons despite administration at 5 year intervals. In the present study we have immunized a group of young adults against tetanus and diphtheria to compare the pre- and 28 days post-vaccination immune responses in the young group with results of the same vaccination performed in an elderly group of a previous study. We also studied prot...

  13. Multidisciplinary approach to the management of a case of classical respiratory diphtheria requiring percutaneous endoscopic gastrostomy feeding.

    Science.gov (United States)

    Haywood, Matthew James; Vijendren, Ananth; Acharya, Vikas; Mulla, Rohinton; Panesar, Miss Jaan

    2017-03-06

    We present a case of a Caucasian woman aged 67 years referred with a 4-day history of sore throat, dysphagia, fever and nasal blockage. Examination revealed a swollen neck and pharyngeal pseudomembrane. A throat swab was positive on culture for Corynebacterium ulcerans, with toxin expression confirmed on PCR and Elek testing. A diagnosis of classical respiratory diphtheria was made, with subsequent confirmation of the patient's domesticated dog as the source of infection. The dog had recently been attacked by a wild badger and was being treated for an ear infection. The patient made a good recovery with intravenous antimicrobial and supportive therapy; however, she subsequently developed a diphtheritic polyneuropathy in the form of a severe bulbar palsy with frank aspiration necessitating percutaneous endoscopic gastrostomy feeding. A mild sensorimotor peripheral neuropathy was also diagnosed. The patient eventually made an almost complete recovery. 2017 BMJ Publishing Group Ltd.

  14. METHODS OF CONTROL DIPHTHERIA VACCINE SAFETY

    Directory of Open Access Journals (Sweden)

    Isayenko Ye. Yu

    2016-12-01

    Full Text Available Vaccination success depends not only on the timely coverage of threatened contingents, but also on the quality of vaccines. Every day, the requirements for security guarantees vaccines and their use guarantees of security increases. For the fast, reliable and independent scientific assessment of vaccine safety issues, WHO in 1999 created the Global Advisory Committee on Vaccine Safety. To enhance the capacity of pharmaceutical supervision in relation to vaccines in 2012 it was developed the Global Vaccine Safety Initiative. The main directions of the Global Vaccine Safety programs are considered in this review. It’s noted more strict requirements of Ukrainian pharmaceutical industry to produce public immunization drugs regulated Supplements to the State Pharmacopoeia of Ukraine, in comparison with other countries. This review considered diphtheria vaccine safety monitoring in the process of production according to the recommendations of the World Health Organization (WHO, described a subcutaneous method for determining the specific toxicity of the combined purified toxoid, characterized an intracutaneous method of determining of the presence of diphtheria toxin in each sample of the combined purified toxoid, that additionally used by some manufacturers. The definition of diphtheria toxin in dilutions of purified toxoid is presented. This review considered diphtheria vaccine safety monitoring in the process of production according to the recommendations of the World Health Organization (WHO, described a subcutaneous method for determining the specific toxicity of the combined purified toxoid, characterized an intracutaneous method of determining of the presence of diphtheria toxin in each sample of the combined purified toxoid, that additionally used by some manufacturers. The definition of diphtheria toxin in dilutions of purified toxoid is presented. As methods for determination of diphtheria toxin must be able to detect even a small amount

  15. Propionibacterium, Corynebacterium, Mycobacterium and Lepra bacilli.

    Science.gov (United States)

    Barksdale, L; Kim, K S

    1984-01-01

    Evidence is presented which suggests that certain key markers of lepra bacilli reside collectively in Proprionibacterium acnes, Corynebacterium tuberculostearicum and Mycobacterium leprae. The unrestricted replication of Mycobacterium leprae depends most probably upon the presence of an immune-deficiency-inducing viral agent or possibly on the combined effects of the organisms considered.

  16. Corynebacterium macginleyi isolated from a corneal ulcer

    Directory of Open Access Journals (Sweden)

    Kathryn Ruoff

    2010-02-01

    Full Text Available We report the isolation of Corynebacterium macginleyi from the corneal ulcer culture of a patient, later enrolled in the Steroids for Corneal Ulcer Trial (SCUT. To our knowledge this is the first published report from North America of the recovery of C. macginleyi from a serious ocular infection.

  17. The Corynebacterium xerosis composite transposon Tn5432 consists of two identical insertion sequences, designated IS1249, flanking the erythromycin resistance gene ermCX.

    Science.gov (United States)

    Tauch, A; Kassing, F; Kalinowski, J; Pühler, A

    1995-09-01

    Analysis of the 50-kb R-plasmid pTP10 from the clinical isolate Corynebacterium xerosis M82B revealed that the erythromycin resistance gene, ermCX, is located on a 4524-bp composite transposable element, Tn5432. The ends of Tn5432 are identical, direct repeats of an insertion sequence, designated IS1249, encoding a putative transposase of the IS256 family. IS1249 consists of 1385 bp with 45/42 imperfect terminal inverted repeats. The nucleotide sequence of the 1754-bp Tn5432 central region is 99% identical to the previously sequenced erythromycin resistance region of the Corynebacterium diphtheriae plasmid pNG2. It encodes the erythromycin resistance gene, ermCX, and an ORF homologous to the amino-terminal end of the transposase of IS31831 from Corynebacterium glutamicum. Transposons with regions flanking the insertion sites were recovered from the C. glutamicum chromosome by a plasmid rescue technique. Insertion of Tn5432 created 8-bp target site duplications. A Tn5432-induced isoleucine/valine-auxotrophic mutant was found to carry the transposon in the 5' region of the ilvBNC cluster; in pTP10 the transposon is inserted in a region similar to replication and partitioning functions of the Enterococcus faecalis plasmid pAD1 and the Agrobacterium tumefaciens plasmid pTAR.

  18. Transgenic tomatoes express an antigenic polypeptide containing epitopes of the diphtheria, pertussis and tetanus exotoxins, encoded by a synthetic gene.

    Science.gov (United States)

    Soria-Guerra, Ruth Elena; Rosales-Mendoza, Sergio; Márquez-Mercado, Crisóforo; López-Revilla, Rubén; Castillo-Collazo, Rosalba; Alpuche-Solís, Angel Gabriel

    2007-07-01

    A current priority of vaccinology is the development of multicomponent vaccines that protect against several pathogens. The diphtheria-pertussis-tetanus (DPT) vaccine prevents the symptoms of three serious and often fatal diseases due to the exotoxins produced by Corynebacterium diphteriae, Bordetella pertussis and Clostridium tetani. We are attempting to develop an edible DPT multicomponent vaccine in plants, based on the fusion of protective exotoxin epitopes encoded by synthetic genes. By means of Agrobacterium mediated transformation we generated transgenic tomatoes with a plant-optimised synthetic gene encoding a novel polypeptide containing two adjuvant and six DPT immunoprotective exotoxin epitopes joined by peptide linkers. In transformed tomato plants, integration of the synthetic DPT (sDPT) gene detected by PCR was confirmed by Southern blot, and specific transcripts of the expected molecular size were detected by RT-PCR. Expression of the putative polypeptide encoded by the sDPT gene was detected by immunoassay with specific antibodies to the diphtheria, pertussis and tetanus exotoxins. The sDPT gene is therefore integrated, transcribed and translated as the expected recombinant sDPT multiepitope polypeptide in transgenic tomatoes that constitute a potential edible vaccine.

  19. Immunogenicity and Safety of Diphtheria-tetanus Vaccine in Adults

    OpenAIRE

    Choi, Jung-Hyun; Choo, Eun Ju; Huh, Aejung; Choi, Su-Mi; Eom, Joong Sik; Lee, Jin Seo; Park, Sun Hee; Kang, Jin Han

    2010-01-01

    This study was conducted to evaluate the immunogenicity and safety of diphtheria-tetanus (Td) vaccine in adults over 40 yr old who had never received a diphtheria-tetanus-pertussis (DTP) vaccination. A total of 242 subject completed three-doses of Td vaccination and subsequent assays for immunogenicity. Before vaccination, 33.9% and 96.7% participants showed antibody levels of diphtheria and tetanus, respectively, which were below protective level (

  20. Implication of Corynebacterium species in food’s contamination

    OpenAIRE

    Sana Alibi; Asma Ferjani; Jalel Boukadida

    2016-01-01

    Corynebacterium spp. are part of the human microbiota. Recently, species of this genus are increasingly implicated in different types of infections especially in immunocompromized and hospitalized patients. The significance of the presence of the genus Corynebacterium in foods is not clearly established. These bacteria may be involved in spoilage or ripening of cheese and meats. This review focused on different researches concerning the implication of Corynebacterium species in...

  1. Implication of Corynebacterium species in food’s contamination

    Directory of Open Access Journals (Sweden)

    Sana Alibi

    2016-05-01

    Full Text Available Corynebacterium spp. are part of the human microbiota. Recently, species of this genus are increasingly implicated in different types of infections especially in immunocompromized and hospitalized patients. The significance of the presence of the genus Corynebacterium in foods is not clearly established. These bacteria may be involved in spoilage or ripening of cheese and meats. This review focused on different researches concerning the implication of Corynebacterium species in food’s contamination.

  2. Tetanus, Diphtheria, and Pertussis Vaccines - Multiple Languages: MedlinePlus

    Science.gov (United States)

    ... Taw) Thiab Pertussis (Hnoos Ntev) - Hmoob (Hmong) PDF Immunization Action Coalition; Centers for Disease Control and Prevention Tetanus, Diphtheria (Td) Vaccine English Tshuaj Txhaj Tiv Thaiv Kab ...

  3. Sudden death of a child due to respiratory diphtheria.

    Science.gov (United States)

    Swain, Rajanikanta; Behera, Chittaranjan; Arava, Sudheer Kumar; Kundu, Naveen

    2016-06-01

    A four-year-old girl presented to the emergency department with respiratory distress. Death occurred despite attempted resuscitation. The illness was not clinically diagnosed. Her father revealed that she had a fever and sore throat for the last four days and was not immunised for diphtheria. Characteristic gross and microscopic pathology of respiratory diphtheria and microbiological findings were observed. The cause of death was acute respiratory failure consequent upon upper airway obstruction from diphtheria. Forensic pathologists should remember that the diphtheria cases can cause sudden death especially in developing countries. © The Author(s) 2016.

  4. 21 CFR 866.3140 - Corynebacterium spp. serological reagents.

    Science.gov (United States)

    2010-04-01

    .... from clinical specimens. The identification aids in the diagnosis of disease caused by bacteria belonging to the genus Corynebacterium and provides epidemiological information on diseases caused by...

  5. Podocyte depletion causes glomerulosclerosis: diphtheria toxin-induced podocyte depletion in rats expressing human diphtheria toxin receptor transgene

    National Research Council Canada - National Science Library

    Wharram, Bryan L; Goyal, Meera; Wiggins, Jocelyn E; Sanden, Silja K; Hussain, Sabiha; Filipiak, Wanda E; Saunders, Thomas L; Dysko, Robert C; Kohno, Kenji; Holzman, Lawrence B; Wiggins, Roger C

    2005-01-01

    .... For determining the causal relationship between podocyte depletion and glomerulosclerosis, a transgenic rat strain in which the human diphtheria toxin receptor is specifically expressed in podocytes was developed...

  6. Resurgence of Diphtheria in North Kerala, India, 2016: Laboratory Supported Case-Based Surveillance Outcomes.

    Science.gov (United States)

    Sangal, Lucky; Joshi, Sudhir; Anandan, Shalini; Balaji, Veeraraghavan; Johnson, Jaichand; Satapathy, Asish; Haldar, Pradeep; Rayru, Ramesh; Ramamurthy, Srinath; Raghavan, Asha; Bhatnagar, Pankaj

    2017-01-01

    As part of national program, laboratory supported vaccine preventable diseases surveillance was initiated in Kerala in 2015. Mechanisms have been strengthened for case investigation, reporting, and data management. Specimens collected and sent to state and reference laboratories for confirmation and molecular surveillance. The major objective of this study is to understand the epidemiological information generated through surveillance system and its utilization for action. Surveillance data captured from reporting register, case investigation forms, and laboratory reports was analyzed. Cases were allotted unique ID and no personal identifying information was used for analysis. Throat swabs were collected from investigated cases as part of surveillance system. All Corynebacterium diphtheriae isolates were confirmed with standard biochemical tests, ELEK's test, and real-time PCR. Isolates were characterized using whole genome-based multi locus sequence typing method. Case investigation forms and laboratory results were recorded electronically. Public health response by government was also reviewed. A total of 533 cases were identified in 11 districts of Kerala in 2016, of which 92% occurred in 3 districts of north Kerala; Malappuram, Kozhikode, and Kannur. Almost 79% cases occurred in >10 years age group. In surveillance for providing real-time information on disease occurrence and mortality is imperative. The epidemiological data thus generated was used for targeted interventions and to formulate vaccine policies. The data on molecular surveillance have given an insight on strain variation and transmission patterns.

  7. External quality assessments for microbiologic diagnosis of diphtheria in Europe.

    Science.gov (United States)

    Both, Leonard; Neal, Shona; De Zoysa, Aruni; Mann, Ginder; Czumbel, Ida; Efstratiou, Androulla

    2014-12-01

    The European Diphtheria Surveillance Network (EDSN) ensures the reliable epidemiological and microbiologic assessment of disease prevalence in the European Union. Here, we describe a survey of current diagnostic techniques for diphtheria surveillance conducted across the European Union and report the results from three external quality assessment (EQA) schemes performed between 2010 and 2014. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  8. Immunogenicity and Safety of Diphtheria-tetanus Vaccine in Adults

    Science.gov (United States)

    Choi, Jung-Hyun; Choo, Eun Ju; Huh, Aejung; Choi, Su-Mi; Eom, Joong Sik; Lee, Jin Seo; Park, Sun Hee

    2010-01-01

    This study was conducted to evaluate the immunogenicity and safety of diphtheria-tetanus (Td) vaccine in adults over 40 yr old who had never received a diphtheria-tetanus-pertussis (DTP) vaccination. A total of 242 subject completed three-doses of Td vaccination and subsequent assays for immunogenicity. Before vaccination, 33.9% and 96.7% participants showed antibody levels of diphtheria and tetanus, respectively, which were below protective level (diphtheria and tetanus, with an increase to 99.6% and 100% after the third dose. Local and systemic adverse events occurred in 37.9% and 15.5% of the subjects. No serious adverse event requiring an unscheduled hospital visit occurred. In conclusion, three-doses of Td vaccination to unimmunized adults are safe and effective in inducing protective immunity against diphtheria and tetanus. PMID:21165286

  9. Diphtheria outbreak with high mortality in northeastern Nigeria.

    Science.gov (United States)

    Besa, N C; Coldiron, M E; Bakri, A; Raji, A; Nsuami, M J; Rousseau, C; Hurtado, N; Porten, K

    2014-04-01

    SUMMARY A diphtheria outbreak occurred from February to November 2011 in the village of Kimba and its surrounding settlements, in Borno State, northeastern Nigeria. We conducted a retrospective outbreak investigation in Kimba village and the surrounding settlements to better describe the extent and clinical characteristics of this outbreak. Ninety-eight cases met the criteria of the case definition of diphtheria, 63 (64.3%) of whom were children aged diphtheria. None of the 98 cases received diphtheria antitoxin, penicillin, or erythromycin during their illness. The overall case-fatality ratio was 21.4%, and was highest in children aged 0-4 years (42.9%). Low rates of immunization, delayed clinical recognition of diphtheria and absence of treatment with antitoxin and appropriate antibiotics contributed to this epidemic and its severity.

  10. Adult vaccination against tetanus and diphtheria: the European perspective.

    Science.gov (United States)

    Weinberger, B

    2017-01-01

    Besides immunizations against influenza, Streptococcus pneumoniae and herpes zoster, which are recommended specifically for elderly people, regular booster vaccinations against tetanus, diphtheria and in some cases pertussis and polio are recommended in many European countries for adults, including elderly people. Vaccination recommendations for adults differ greatly between individual countries and coverage data is scarce. Tetanus-specific antibody concentrations are generally higher than diphtheria-specific antibodies, and a substantial proportion of adults, and particularly of elderly people, do not have protective antibody concentrations against diphtheria. Antibody levels increase upon booster vaccination in all age groups, but diphtheria-specific antibody concentrations remain below protective levels in some older individuals, even immediately after vaccination and long-term protection is frequently not achieved. Future vaccination strategies should therefore include regular and well-documented booster shots, e.g. against tetanus and diphtheria, throughout life. © 2016 British Society for Immunology.

  11. Immunogenicity and safety of diphtheria-tetanus vaccine in adults.

    Science.gov (United States)

    Choi, Jung-Hyun; Choo, Eun Ju; Huh, Aejung; Choi, Su-Mi; Eom, Joong Sik; Lee, Jin Seo; Park, Sun Hee; Kang, Jin Han

    2010-12-01

    This study was conducted to evaluate the immunogenicity and safety of diphtheria-tetanus (Td) vaccine in adults over 40 yr old who had never received a diphtheria-tetanus-pertussis (DTP) vaccination. A total of 242 subject completed three-doses of Td vaccination and subsequent assays for immunogenicity. Before vaccination, 33.9% and 96.7% participants showed antibody levels of diphtheria and tetanus, respectively, which were below protective level (antibody concentrations (≥ 0.1 U/mL) for diphtheria and tetanus, with an increase to 99.6% and 100% after the third dose. Local and systemic adverse events occurred in 37.9% and 15.5% of the subjects. No serious adverse event requiring an unscheduled hospital visit occurred. In conclusion, three-doses of Td vaccination to unimmunized adults are safe and effective in inducing protective immunity against diphtheria and tetanus.

  12. Difteria pelo Corynebacterium ulcerans: uma zoonose emergente no Brasil e no mundo

    Directory of Open Access Journals (Sweden)

    Alexandre Alves de Souza de Oliveira Dias

    2011-12-01

    Full Text Available O artigo revisa a literatura sobre a emergência de infecções humanas causadas por Corynebacterium ulcerans em diversos países, incluindo o Brasil. Foi realizada análise de artigos publicados entre 1926 e 2011 nas bases Medline/PubMed e SciELO, bem como artigos e informes do Ministério da Saúde. Apresenta-se um esquema de triagem, rápido, econômico e de fácil execução, capaz de permitir a realização do diagnóstico presuntivo de C. ulcerans e C. diphtheriae na maioria dos laboratórios brasileiros públicos e privados. A circulação de C. ulcerans em vários países, aliada aos recentes casos de isolamento do patógeno no Rio de Janeiro, é um alerta a clínicos, veterinários e microbiologistas sobre a ocorrência de difteria zoonótica e a circulação do C. ulcerans em regiões urbanas e rurais do território nacional e/ou da América Latina.

  13. Codon Usage Patterns in Corynebacterium glutamicum: Mutational Bias, Natural Selection and Amino Acid Conservation

    Directory of Open Access Journals (Sweden)

    Guiming Liu

    2010-01-01

    Full Text Available The alternative synonymous codons in Corynebacterium glutamicum, a well-known bacterium used in industry for the production of amino acid, have been investigated by multivariate analysis. As C. glutamicum is a GC-rich organism, G and C are expected to predominate at the third position of codons. Indeed, overall codon usage analyses have indicated that C and/or G ending codons are predominant in this organism. Through multivariate statistical analysis, apart from mutational selection, we identified three other trends of codon usage variation among the genes. Firstly, the majority of highly expressed genes are scattered towards the positive end of the first axis, whereas the majority of lowly expressed genes are clustered towards the other end of the first axis. Furthermore, the distinct difference in the two sets of genes was that the C ending codons are predominate in putatively highly expressed genes, suggesting that the C ending codons are translationally optimal in this organism. Secondly, the majority of the putatively highly expressed genes have a tendency to locate on the leading strand, which indicates that replicational and transciptional selection might be invoked. Thirdly, highly expressed genes are more conserved than lowly expressed genes by synonymous and nonsynonymous substitutions among orthologous genes fromthe genomes of C. glutamicum and C. diphtheriae. We also analyzed other factors such as the length of genes and hydrophobicity that might influence codon usage and found their contributions to be weak.

  14. Diphtheria outbreak in Thailand, 2012; seroprevalence of diphtheria antibodies among Thai adults and its implications for immunization programs.

    Science.gov (United States)

    Wanlapakorn, Nasamon; Yoocharoen, Pornsak; Tharmaphornpilas, Piyanit; Theamboonlers, Apiradee; Poovorawan, Yong

    2014-09-01

    An age distribution shift in diphtheria cases during a 2012 outbreak in northeastern of Thailand suggests adults are increasingly at risk for infection in Thailand. Data regarding immunity against diphtheria among the adult Thai population is limited. We review a 2012 diphtheria outbreak in Thailand and conducted a nationwide seroepidemiological survey to determine the prevalence of diphtheria antibodies among Thai adults in order to inform immunization programs. A total of 41 confirmed cases, 6 probable cases and 101 carriers of diphtheria were reported from northeastern and upper southern Thailand. The diphtheria outbreak in northeastern Thailand occurred among adults aged > or =15 years; sporadic cases occurred among children from upper southern Thailand. We conducted a seroepidemiological survey of 890 Thai adults from 4 age groups (20-29, 30-39, 40-49 and 50-59 years) in 7 different geographical areas of Thailand (Chiang Mai, Ratchaburi, Chon Buri, Nakhon Si Thammarat, Phitsanulok, Khon Kaen and Songkhla). Diptheria toxin antibody levels were measured with a commercially available ELISA test. The seroprotection rate ranged from 83% to 99%, with the highest in eastern Thailand (Chon Buri, 99%) and the lowest in northern Thailand (Chiang Mai, 83%). Diphtheria antibodies declined with increasing age. We recommend one doseof diphtheria-tetanus toxoid (dT) vaccine once after 20 years of age in order to boost the antibody and revaccinations every 10 years to prevent future outbreaks.

  15. The killing of macrophages by Corynebacterium ulcerans.

    Science.gov (United States)

    Hacker, Elena; Ott, Lisa; Schulze-Luehrmann, Jan; Lührmann, Anja; Wiesmann, Veit; Wittenberg, Thomas; Burkovski, Andreas

    2016-01-01

    Corynebacterium ulcerans is an emerging pathogen transmitted by a zoonotic pathway with a very broad host spectrum to humans. Despite rising numbers of infections and potentially fatal outcomes, data on the molecular basis of pathogenicity are scarce. In this study, the interaction of 2 C. ulcerans isolates - one from an asymptomatic dog, one from a fatal case of human infection - with human macrophages was investigated. C. ulcerans strains were able to survive in macrophages for at least 20 hours. Uptake led to delay of phagolysosome maturation and detrimental effects on the macrophages as deduced from cytotoxicity measurements and FACS analyses. The data presented here indicate a high infectious potential of this emerging pathogen.

  16. A diphtheria outbreak in Buri Ram, Thailand.

    Science.gov (United States)

    Pantukosit, Pantavee; Arpornsuwan, Manote; Sookananta, Kanokporn

    2008-07-01

    In May 1996 there was an outbreak of diphtheria in Buri Ram, Thailand which infected 31 patients, 8 males and 23 females. The mean age of the patients was 8 +/- 5 years. Seventy-four percent had a history of childhood vaccinations. Common signs and symptoms included fever (100%) which was low grade in 61%, sore throat (90%), upper airway obstruction (3%), and hoarseness (10%). Pseudomembranes (seen in 100%) were located on the tonsils (71%), pharynx (22%), larynx (9.6%), and uvula (6%). The mean duration of symptoms prior to admission was 2 days with a range of 1 to 5 days. Complications included upper airway obstruction (10%) and cardiac complications (10%). There were no neurological complication or deaths. There were negative associations between cardiac complications, severity of disease and previous diphtheria vaccination. The ages varied from children to adults. Early recognition and prompt treatment decreased complications and mortality in this group of patients when compared with Chiang Mai and Queen Sirikit National Institute of Child Health (QSNICH) studies.

  17. Diphtheria outbreak in Lao People's Democratic Republic, 2012-2013.

    Science.gov (United States)

    Sein, Carolyn; Tiwari, Tejpratap; Macneil, Adam; Wannemuehler, Kathleen; Soulaphy, Chanthavy; Souliphone, Phouthone; Reyburn, Rita; Ramirez Gonzalez, Alejandro; Watkins, Margaret; Goodson, James L

    2016-08-05

    Diphtheria is a vaccine-preventable disease. When vaccination coverage and population immunity are low, outbreaks can occur. We investigated a diphtheria outbreak in Lao People's Democratic Republic that occurred during 2012-2013 and highlighted challenges in immunization services delivery to children in the country. We reviewed diphtheria surveillance data from April 1, 2012-May 31, 2013. A diphtheria case was defined as a respiratory illness consisting of pharyngitis, tonsillitis, or laryngitis, and an adherent tonsillar or nasopharyngeal pseudomembrane. To identify potential risk factors for diphtheria, we conducted a retrospective case-control study with two aged-matched neighborhood controls per case-patient in Houaphan Province, using bivariate analysis to calculate matched odds ratio (mOR) with 95% confidence intervals (CI). Reasons for non-vaccination among unvaccinated persons were assessed. Sixty-two clinical cases of diphtheria and 12 diphtheria-related deaths were reported in seven of 17 provinces. Among case-patients, 43 (69%) were diphtheria case-patients from Houaphan province and 79 matched-controls were enrolled. Five (12%) case-patients and 20 (25%) controls had received DTP3 (mOR=0.4, CI=0.1-1.7). No diphtheria toxoid-containing vaccine was received by 20 (48%) case-patients and 38 (46%) controls. Among case-patients and controls with no DTP dose, 43% of case-patients and 40% of controls lacked access to routine immunization services. Suboptimal DTP3 coverage likely caused the outbreak. To prevent continued outbreaks, access to routine immunization services should be strengthened, outreach visits need to be increased, and missed opportunities need to be minimized. In the short term, to rapidly increase population immunity, three rounds of DTP immunization campaign should be completed, targeting children aged 0-14years in affected provinces. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Cutaneous diphtheria masquerading as a sexually transmitted disease

    Directory of Open Access Journals (Sweden)

    Vetrichevvel T

    2008-01-01

    Full Text Available A 41 year-old, sexually promiscuous, married male, an agricultural laborer by occupation, presented to our sexually transmitted diseases (STD clinic with multiple ulcers over the scrotum and genitalia of 20 days′ duration. Bacterial culture from swabs taken from the genital ulcer, grew organisms morphologically and biochemically characteristic of Corynaebacterium diphtheriae. He made a complete and uneventful recovery after two weeks of therapy with antidiphtheria serum and crystalline penicillin. This case brings into light this hitherto unreported presentation of wound diphtheria mimicking a sexually transmitted genital ulcer disease and thus, underlines the importance of considering diphtheria as differential in atypical, long-standing genital ulcers.

  19. NMR study of Corynebacterium melassecola metabolism; Etude du metabolisme de corynebacterium melassecola par RMN

    Energy Technology Data Exchange (ETDEWEB)

    Rollin, C.; Morgant, V.; Guyonvarch, A. [Centre ORSAN, 91 - Les Ulis (France); Guerquin Kern, J.L. [Institut Curie, 91 - Orsay (France)

    1994-12-31

    Corynebacterium melassecola is a microorganism producing glutamic acid, an aminate acid used as food additive. Knowledge of its metabolism is essential for improving the phyla. A study is carried out on intracellular extracts with NMR spectrometry in order to determine certain glucose catabolism pathways using a partial isotopic enrichment with (1-{sup 13}C) or (6-{sup 13}C) glucose. Results demonstrate the particular metabolism of Corynebacteria. 2 tabs., 3 refs.

  20. Td (tetanus and diphtheria) vaccine - what you need to know

    Science.gov (United States)

    ... February 24, 2015 Content source: National Center for Immunization and Respiratory Diseases ... reported in the United States each year. Since vaccination began, ... tetanus and diphtheria. Td is usually given as a booster dose ...

  1. Td Vaccine (Tetanus and Diphtheria): What You Need to Know

    Science.gov (United States)

    VACCINE INFORMATION STATEMENT Td Vaccine (Tetanus and Diphtheria) What You Need to Know Many Vaccine Information Statements are available in Spanish and other languages. See www. immunize. org/ vis Hojas de ...

  2. Efficacy of diphtheria and tetanus vaccination in Gaza, Palestine.

    Science.gov (United States)

    Al Aswad, I H; Shubair, M E

    2009-01-01

    This study evaluated the effectiveness and usefulness of vaccination against diphtheria and tetanus in different age groups in Gaza, Palestine. Blood samples were collected from 180 children aged ELISA methods, the efficacy of vaccination was estimated at 87.8% for diphtheria and 98.3% for tetanus. Mean serum titres varied significantly by age group: for diphtheria 0.24 IU/mL at age 2-4 years, 0.63 IU/mL at 7-8 years and 0.46 IU/mL at 11-12 years, and for tetanus 1.01 IU/mL, 2.63 IU/mL and 1.20 IU/mL respectively. The relatively low antibody titres, especially for diphtheria, suggest the need for a booster dose.

  3. Immunity against diphtheria among children and adults in Izmir, Turkey.

    Science.gov (United States)

    Kurugöl, Zafer; Midyat, Levent; Türkoğlu, Ebru; Işler, Ayşegül

    2011-06-10

    The aim of this study was to evaluate diphtheria immunity in a sample of the Turkish population having high childhood immunization coverage, including a booster dose of diphtheria toxoid at 12-15 years of age. A total of 599 persons aged 1-70 years were selected with cluster sampling. The information on socio-demographic characteristics, vaccination status and diphtheria history was gathered for each participant. Diphtheria antitoxin levels were measured qualitatively by using micro-enzyme immune assay. Of studied population, 72.3% had fully protective antitoxin levels (≥ 0.1 IU/ml). The rate of protection was 92.5% in the children aged 0-2 years, 93.2% in the primary school children aged 7-9 years, and 86.0% in the adolescents aged 15-19 years. After 20 years of age, diphtheria protection rates showed a significant age-related decrease, reaching minimum in the 30-39 age group, in which 47.3% of these subjects had fully protective antitoxin levels. The diphtheria antitoxin geometric mean titer (GMT) was highest in the 0-2 year age group (1.18 IU/ml). In the adolescents aged 15-19 years, diphtheria antitoxin GMT was 0.71 IU/ml. Then, geometric mean titer decreased with increasing age, and reached the minimum level in the 40-59 years age group (0.18 IU/ml). The protection rate among females was significantly lower than males (67.1% vs. 80.9%). The difference was apparent in the 20-29 and the 30-39 years age group: 80% of the males and 46.2% of the females in the 20-29 years age group, and 60% of males and 44.1% of females in the 30-39 years age group were fully protected against diphtheria (pdiphtheria is only detectable in diphtheria outbreaks among the adults in our country. Therefore, a revaccination of adults with reduced doses of diphtheria toxoid should be considered to sustain diphtheria immunity. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Immunity to tetanus and diphtheria in the UK in 2009.

    Science.gov (United States)

    Wagner, Karen S; White, Joanne M; Andrews, Nick J; Borrow, Ray; Stanford, Elaine; Newton, Emma; Pebody, Richard G

    2012-11-19

    This study aimed to estimate the immunity of the UK population to tetanus and diphtheria, including the potential impact of new glycoconjugatate vaccines, and the addition of diphtheria to the school leaver booster in 1994. Residual sera (n=2697) collected in England in 2009/10 were selected from 18 age groups and tested for tetanus and diphtheria antibody. Results were standardised by testing a panel of sera (n=150) to enable comparison with a previously (1996) published serosurvey. Data were then standardised to the UK population. In 2009, 83% of the UK population were protected (≥0.1 IU/mL) against tetanus compared to 76% in 1996 (p=0.079), and 75% had at least basic protection against diphtheria (≥0.01 IU/mL) in 2009 compared to 60% in 1996 (pdiphtheria. Higher diphtheria immunity was observed in those aged 16-34 years in 2009 compared to 1996 (geometric mean concentration [GMC] 0.15 IU/mL vs. 0.03 IU/mL, pdiphtheria in 2009 were 29% susceptible), 45-69 years (>20% susceptible) and 70+ years (>32% susceptible). Low immunity was observed in those aged 10-11 years (>19% susceptible), between the scheduled preschool and school leaver booster administration. The current schedule appears to induce protective levels; increases in the proportions protected/GMCs were observed for the ages receiving vaccinations according to UK policy. Glycoconjugate vaccines appear to have increased immunity, in particular for diphtheria, in preschool age groups. Diphtheria immunity in teenagers and young adults has increased as a result of the addition of diphtheria to the school leaver booster. However, currently older adults remain susceptible, without any further opportunities for immunisations planned according to the present schedule. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Implication ofCorynebacterium species in food’s contamination

    Institute of Scientific and Technical Information of China (English)

    Sana Alibi; Asma Ferjani; Jalel Boukadida

    2016-01-01

    Corynebacteriumspp. are part of the human microbiota. Recently, species of this genus are increasingly implicated in different types of infections especially in immunocompromized and hospitalized patients. The significance of the presence of the genusCorynebacterium in foods is not clearly established. These bacteria may be involved in spoilage or ripening of cheese and meats. This review focused on different researches concerning the implication of Corynebacterium species in food’s contamination.

  6. Corynebacterium pyruviciproducens, as an immune modulator, can promote the activity of macrophages and up-regulate antibody response to particulate antigen.

    Science.gov (United States)

    Tong, Jia; Han, Qingzhen; Wang, Shengjun; Su, Zhaoliang; Zheng, Dong; Shen, Pei; Xia, Sheng; Huang, Xinxiang; Shao, Qixiang; Xu, Huaxi

    2012-11-01

    Corynebacterium pyruviciproducens is a newly discovered Corynebacterium species with no known pathogenic components such as diphtheria toxin and tuberculostearic acid, and it has similar biological properties to Propionibacterium acnes, but its role of immunoregulation is drawing people's attention. In this work, based on the role of macrophages in removal of pathogenic bacteria as a primary scavenger and particulate antigen-presenting cell, the stimulation of macrophages by C. pyruviciproducens was analyzed through detecting the levels of cytokine secretion and expression of membrane molecules, and the effect of C. pyruviciproducens in promoting antibody response to sheep red blood cells (SRBC) in vivo was detected. In vitro, C. pyruviciproducens led to a sharp release of interleukin-6 and tumour necrosis factor-α and encouraged the activation of macrophages including enhanced expressions of MHC-II, CD40, CD80 and CD86. In vivo, it enhanced the humoral immune response against SRBC, a particulate antigen. These observations suggest that C. pyruviciproducens, as an immunoregulator, can promote the host humoral immune response to pathogenic microorganisms by regulating macrophage function.

  7. The Actinobacterium Corynebacterium glutamicum, an Industrial Workhorse.

    Science.gov (United States)

    Lee, Joo-Young; Na, Yoon-Ah; Kim, Eungsoo; Lee, Heung-Shick; Kim, Pil

    2016-05-28

    Starting as a glutamate producer, Corynebacterium glutamicum has played a variety of roles in the industrial production of amino acids, one of the most important areas of white biotechnology. From shortly after its genome information became available, C. glutamicum has been applied in various production processes for value-added chemicals, fuels, and polymers, as a key organism in industrial biotechnology alongside the surprising progress in systems biology and metabolic engineering. In addition, recent studies have suggested another potential for C. glutamicum as a synthetic biology platform chassis that could move the new era of industrial microbial biotechnology beyond the classical field. Here, we review the recent progress and perspectives in relation to C. glutamicum, which demonstrate it as one of the most promising and valuable workhorses in the field of industrial biotechnology.

  8. 蜂胶对白喉杆菌的抑菌试验%Antibacterial activity of propolis against Corynebacterium diphtheriae

    Institute of Scientific and Technical Information of China (English)

    曾莉萍; 许兵红; 李进芬

    2008-01-01

    目的 探讨河南蜂胶对白喉杆菌的抑菌效果. 方法 采用琼脂平板扩散法,以白喉杆菌为实验菌种,设置不同pH平板实验组和不同的蜂胶浓度组,每组3次重复,每张滤纸片(直径6 mm)加样7 μl,记录24 h的抑菌效果. 结果 河南蜂胶在pH 5.5、6.0、6.5、7.0、7.5、8.0和8.5不同条件下对白喉杆菌的抑菌环直径(mm)分别为:14.50±0.50、10.83±0.76、10.66±0.2 9、10.42±1.38、9.92±0.14、9.83±0.29和9.92±0.14.蜂胶浓度从15.50%倍比稀释至0.50%时对白喉杆菌的抑菌环直径(mm)依次为:12.50±1.00、11.50±0.87、11.33±0.76、9.67±0.29、9.17±0.58和7.75±0.25,≤0.25%浓度组和空白对照组均无抑菌环. 结论 随pH增高,河南蜂胶对白喉杆菌的抑菌活性减弱.随着蜂胶浓度降低,对白喉杆菌的抑菌活力减弱,最低抑菌浓度为0.50%.

  9. Diphtheria and the Vaccine (Shot) to Prevent It: Information for Parents

    Science.gov (United States)

    ... PARENTS | DISEASES and the VACCINES THAT PREVENT THEM | Diphtheria and the Vaccine (Shot) to Prevent It Last ... April 2017 The best way to protect against diphtheria is by getting the diphther ia-tet anus- ...

  10. DTaP Vaccine (Diphtheria, Tetanus, and Pertussis): What You Need to Know

    Science.gov (United States)

    ... DTaP Vaccine What You Need to Know (Diphtheria, Tetanus and Pertussis) Many Vaccine Information Statements are available ... immunize. org/ vis 1 Why get vaccinated? Diphtheria, tetanus, and pertussis are serious diseases caused by bacteria . ...

  11. Diphtheria, tetanus, and pertussis (DTaP) vaccines - what you need to know

    Science.gov (United States)

    ... taken in its entirety from the CDC Diphtheria, Tetanus, and Pertussis (DTaP) Vaccine Information Statement (VIS): www. ... statements/dtap.html CDC review information for Diphtheria, Tetanus, and Pertussis (DTaP) VIS: Page last reviewed: June ...

  12. CLINICAL FEATURES OF CHILDREN WITH DIPHTHERIA ON SOETOMO HOSPITAL

    Directory of Open Access Journals (Sweden)

    Dwiyanti Puspitasari

    2017-04-01

    Full Text Available Introduction: Diphtheria is an important disease in children that could lead to fatal disease. East Java Province was declared to have Diphtheria outbreak in 2011 with increasing morbidity and mortality, including on Soetomo Hospital. Our paper aimed to describe the profi le of diphtheria cases in children admitted at dr Sutomo Hospital. Method: This descriptive study reviewed all medical records of diphtheritic patients admitted to Dr. Soetomo Hospital, January 2004–December 2010, of concerns were clinical presentations, age, sex, immunizations status, complications, and outcomes. Result: From 148 diphtheria cases, 22.3% were bacteriologically proven; 53.4% were male with sex ratio 1.1:1. The age proportion of ≤ 5 years old, 5- ≤ 10 years old, and > 10 years old were 61.5%, 31.8%, and 6.7%. Fever occurred in 99% cases, sore throat, stridor and bullneck occurred respectively in 62.2%, 39.9%, and 29.7% cases. There were 56.8% severe and 41.9% moderate diphtheria. Subjects were immunized in 84%, but none of them have adequate immunization. Myocarditis, being one of the commonest complications occurred in 11.4% cases and tracheostomy was the second (4.0%. All of the death cases (7.9% were unvaccinated and in severe form. Discussion: The mostly prevalent clinical manifestations in diphtheria children were fever and sore throat. Half of the cases came with severe diphtheria and most cases were inadequately vaccinated. Death occurred in the unvaccinated and severe form.

  13. Staphylococcus aureus Shifts toward Commensalism in Response to Corynebacterium Species.

    Science.gov (United States)

    Ramsey, Matthew M; Freire, Marcelo O; Gabrilska, Rebecca A; Rumbaugh, Kendra P; Lemon, Katherine P

    2016-01-01

    Staphylococcus aureus-human interactions result in a continuum of outcomes from commensalism to pathogenesis. S. aureus is a clinically important pathogen that asymptomatically colonizes ~25% of humans as a member of the nostril and skin microbiota, where it resides with other bacteria including commensal Corynebacterium species. Commensal Corynebacterium spp. are also positively correlated with S. aureus in chronic polymicrobial diabetic foot infections, distinct from acute monomicrobial S. aureus infections. Recent work by our lab and others indicates that microbe-microbe interactions between S. aureus and human skin/nasal commensals, including Corynebacterium species, affect S. aureus behavior and fitness. Thus, we hypothesized that S. aureus interactions with Corynebacterium spp. diminish S. aureus virulence. We tested this by assaying for changes in S. aureus gene expression during in vitro mono- versus coculture with Corynebacterium striatum, a common skin and nasal commensal. We observed a broad shift in S. aureus gene transcription during in vitro growth with C. striatum, including increased transcription of genes known to exhibit increased expression during human nasal colonization and decreased transcription of virulence genes. S. aureus uses several regulatory pathways to transition between commensal and pathogenic states. One of these, the quorum signal accessory gene regulator (agr) system, was strongly inhibited in response to Corynebacterium spp. Phenotypically, S. aureus exposed to C. striatum exhibited increased adhesion to epithelial cells, reflecting a commensal state, and decreased hemolysin activity, reflecting an attenuation of virulence. Consistent with this, S. aureus displayed diminished fitness in experimental in vivo coinfection with C. striatum when compared to monoinfection. These data support a model in which S. aureus shifts from virulence toward a commensal state when exposed to commensal Corynebacterium species.

  14. Staphylococcus aureus shifts towards commensalism in response to Corynebacterium species

    Directory of Open Access Journals (Sweden)

    Matthew M Ramsey

    2016-08-01

    Full Text Available Staphylococcus aureus–human interactions result in a continuum of outcomes from commensalism to pathogenesis. S. aureus is a clinically important pathogen that asymptomatically colonizes ~25% of humans as a member of the nostril and skin microbiota, where it resides with other bacteria including commensal Corynebacterium species. Commensal Corynebacterium spp. are also positively correlated with S. aureus in chronic polymicrobial diabetic foot infections, distinct from acute monomicrobial S. aureus infections. Recent work by our lab and others indicates that microbe-microbe interactions between S. aureus and human skin/nasal commensals, including Corynebacterium species, affect S. aureus behavior and fitness. Thus, we hypothesized that S. aureus interactions with Corynebacterium spp. diminish S. aureus virulence. We tested this by assaying for changes in S. aureus gene expression during in vitro mono- versus coculture with Corynebacterium striatum, a common skin and nasal commensal. We observed a broad shift in S. aureus gene transcription during in vitro growth with C. striatum, including increased transcription of genes known to exhibit increased expression during human nasal colonization and decreased transcription of virulence genes. S. aureus uses several regulatory pathways to transition between commensal and pathogenic states. One of these, the quorum signal accessory gene regulator (agr system, was strongly inhibited in response to Corynebacterium spp. Phenotypically, S. aureus exposed to C. striatum exhibited increased adhesion to epithelial cells, reflecting a commensal state, and decreased hemolysin activity, reflecting an attenuation of virulence. Consistent with this, S. aureus displayed diminished fitness in experimental in vivo coinfection with C. striatum when compared to monoinfection. These data support a model in which S. aureus shifts from virulence towards a commensal state when exposed to commensal Corynebacterium species.

  15. Seroprevalence of diphtheria toxoid IgG antibodies in children, adolescents and adults in Poland

    OpenAIRE

    Zasada, Aleksandra A.; Rastawicki, Waldemar; Rokosz, Natalia; Jagielski, Marek

    2013-01-01

    Background Recommendations for diphtheria immunization are to apply an effective primary immunization in infancy and to maintain immunity throughout life. Immunity against diphtheria depends primarily on antibody to the diphtheria toxin. This study evaluated the seroprevalence of IgG diphtheria antitoxin in sera of healthy children, adolescents and adults in Poland. Methods A total of 1387 serum samples collected between 2010 and 2012 from individuals with ages ranging from 1 month to 85 year...

  16. Diphtheria in Lao PDR: Insufficient Coverage or Ineffective Vaccine?

    Directory of Open Access Journals (Sweden)

    Naphavanh Nanthavong

    Full Text Available During late 2012 and early 2013 several outbreaks of diphtheria were notified in the North of the Lao People's Democratic Republic. The aim of this study was to determine whether the re-emergence of this vaccine-preventable disease was due to insufficient vaccination coverage or reduction of vaccine effectiveness within the affected regions.A serosurvey was conducted in the Huaphan Province on a cluster sampling of 132 children aged 12-59 months. Serum samples, socio-demographic data, nutritional status and vaccination history were collected when available. Anti-diphtheria and anti-tetanus IgG antibody levels were measured by ELISA.Overall, 63.6% of participants had detectable diphtheria antibodies and 71.2% tetanus antibodies. Factors independently associated with non-vaccination against diphtheria were the distance from the health centre (OR: 6.35 [95% CI: 1.4-28.8], p = 0.01, the Lao Theung ethnicity (OR: 12.2 [95% CI:1,74-85, 4], p = 0.01 and the lack of advice on vaccination given at birth (OR: 9.8 [95% CI: 1.5-63.8], (p = 0.01 while the level of maternal edu-cation was a protective factor (OR: 0.08 [95% CI: 0.008-0.81], p = 0.03. Most respondents claimed financial difficulties as the main reason for non-vaccination. Out of 55 children whose vaccination certificates stated that they were given all 3 doses of diphtheria-containing vaccine, 83.6% had diphtheria antibodies and 92.7% had tetanus antibodies. Furthermore, despite a high prevalence of stunted and underweight children (53% and 25.8%, respectively, the low levels of anti-diphtheria antibodies were not correlated to the nutritional status.Our data highlight a significant deficit in both the vaccination coverage and diphtheria vaccine effectiveness within the Huaphan Province. Technical deficiencies in the methods of storage and distribution of vaccines as well as unreliability of vaccination cards are discussed. Several hypotheses are advanced to explain such a decline in immunity

  17. Diphtheria in Lao PDR: Insufficient Coverage or Ineffective Vaccine?

    Science.gov (United States)

    Nanthavong, Naphavanh; Black, Antony P; Nouanthong, Phonethipsavanh; Souvannaso, Chanthasone; Vilivong, Keooudomphone; Muller, Claude P; Goossens, Sylvie; Quet, Fabrice; Buisson, Yves

    2015-01-01

    During late 2012 and early 2013 several outbreaks of diphtheria were notified in the North of the Lao People's Democratic Republic. The aim of this study was to determine whether the re-emergence of this vaccine-preventable disease was due to insufficient vaccination coverage or reduction of vaccine effectiveness within the affected regions. A serosurvey was conducted in the Huaphan Province on a cluster sampling of 132 children aged 12-59 months. Serum samples, socio-demographic data, nutritional status and vaccination history were collected when available. Anti-diphtheria and anti-tetanus IgG antibody levels were measured by ELISA. Overall, 63.6% of participants had detectable diphtheria antibodies and 71.2% tetanus antibodies. Factors independently associated with non-vaccination against diphtheria were the distance from the health centre (OR: 6.35 [95% CI: 1.4-28.8], p = 0.01), the Lao Theung ethnicity (OR: 12.2 [95% CI:1,74-85, 4], p = 0.01) and the lack of advice on vaccination given at birth (OR: 9.8 [95% CI: 1.5-63.8], (p = 0.01) while the level of maternal edu-cation was a protective factor (OR: 0.08 [95% CI: 0.008-0.81], p = 0.03). Most respondents claimed financial difficulties as the main reason for non-vaccination. Out of 55 children whose vaccination certificates stated that they were given all 3 doses of diphtheria-containing vaccine, 83.6% had diphtheria antibodies and 92.7% had tetanus antibodies. Furthermore, despite a high prevalence of stunted and underweight children (53% and 25.8%, respectively), the low levels of anti-diphtheria antibodies were not correlated to the nutritional status. Our data highlight a significant deficit in both the vaccination coverage and diphtheria vaccine effectiveness within the Huaphan Province. Technical deficiencies in the methods of storage and distribution of vaccines as well as unreliability of vaccination cards are discussed. Several hypotheses are advanced to explain such a decline in immunity against

  18. Anti-diphtheria immunity in Nigerian mothers and their newborns.

    Science.gov (United States)

    Cummings, Henry; Sadoh, Ayebo Evawere; Oviawe, Osawaru; Sadoh, Wilson Ehidiamen

    2014-05-30

    Immunity to diphtheria has been noted to wane with age such that previous studies have shown that a significant proportion of females with characteristics comparable to those of Nigerian women of reproductive age have inadequate levels of immunity to diphtheria. Thus, it is envisaged that Nigerian newborns may inherit inadequate levels of immunity to diphtheria from their mothers. Cord blood and peripheral maternal blood samples were collected from 231 mother-infant pairs at delivery. Anti-diphtheria antibody titres were assayed using Enzyme-linked immunosorbent assay (ELISA) technique. Recruited babies were those born at term with normal birth weight. As much as 29.9% of both mothers and their babies had no protection (antibody titrediphtheria. Ninety (39.0% CI 33%,45%) mothers and 107 (46.3% CI 40%,52%) babies were inadequately protected (antibody titrediphtheria. The difference in the geometric mean antibody titres of mothers and babies was statistically significant (pdiphtheria. Vaccination of parturient women with booster doses of diphtheria toxoid vaccine is recommended. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. [Production and characteristics of monoclonal antibodies to the diphtheria toxin].

    Science.gov (United States)

    Valiakina, T I; Lakhtina, O E; Komaleva, R L; Simonova, M A; Samokhvalova, L V; Shoshina, N S; Kalinina, N A; Rubina, A Iu; Filippova, M A; Vertiev, Iu V; Grishin, E V

    2009-01-01

    Monoclonal antibodies to the diphtheria toxin were produced without cross reactivity with the thermolabile toxin (LT) from Escherichia coli; ricin; choleraic toxin; the SeA, SeB, SeE, SeI, and SeG toxins of staphylococcus; the lethal factor of the anthrax toxin; and the protective antigen of the anthrax toxin. A pair of antibodies for the quantitative determination of the diphtheria toxin in the sandwich variation of enzyme-linked immunosorbent assay (ELISA) was chosen. The determination limit of the toxin was 0.7 ng/ml in plate and 1.6 ng/ml in microchip ELISA. The presence of a secretion from the nasopharynx lavage did not decrease the sensitivity of the toxin determination by sandwich ELISA. The immunization of mice with the diphtheria toxin and with a conjugate of the diphtheria toxin with polystyrene microspheres demonstrated that the conjugate immunization resulted in the formation of hybridoma clones which produced antibodies only to the epitopes of the A fragment of the diphtheria toxin. The immunization with the native toxin caused the production of hybridoma clones which predominantly produced antibodies to the epitopes of the B fragment.

  20. 疑似白喉误诊一例分析%Analysis of misdiagnosis for 1 cases suspected diphtheria

    Institute of Scientific and Technical Information of China (English)

    张雪; 毛雯雯; 张东彦; 唐田; 余红

    2012-01-01

    白喉是由白喉杆菌(Corynebacterium diphtheriae)引起的一种急性呼吸道传染病,其临床典型特征为鼻、咽、喉等处黏膜充血、肿胀,有灰白色假膜形成,以及外毒素引起的中毒症状.儿童青少年均易感,曾对该人群健康危害极大.我国自20世纪70年代广泛开展白喉类疫苗接种以来,该病得到有效控制,2000年至今除个别省个别年份有病例报告外,已连续多年无病例报告.北京市自1996年已连续15年无病例报告.2011年8月11日北京市丰台区疾病预防控制中心计划免疫科接到本市传染病医院收治一例白喉疑似病例的电话报告.为此进行该病例的流行病学调查及处理,现将结果分析如下.

  1. Insights into Diphthamide, Key Diphtheria Toxin Effector

    Directory of Open Access Journals (Sweden)

    Raffael Schaffrath

    2013-05-01

    Full Text Available Diphtheria toxin (DT inhibits eukaryotic translation elongation factor 2 (eEF2 by ADP-ribosylation in a fashion that requires diphthamide, a modified histidine residue on eEF2. In budding yeast, diphthamide formation involves seven genes, DPH1-DPH7. In an effort to further study diphthamide synthesis and interrelation among the Dph proteins, we found, by expression in E. coli and co-immune precipitation in yeast, that Dph1 and Dph2 interact and that they form a complex with Dph3. Protein-protein interaction mapping shows that Dph1-Dph3 complex formation can be dissected by progressive DPH1 gene truncations. This identifies N- and C-terminal domains on Dph1 that are crucial for diphthamide synthesis, DT action and cytotoxicity of sordarin, another microbial eEF2 inhibitor. Intriguingly, dph1 truncation mutants are sensitive to overexpression of DPH5, the gene necessary to synthesize diphthine from the first diphthamide pathway intermediate produced by Dph1-Dph3. This is in stark contrast to dph6 mutants, which also lack the ability to form diphthamide but are resistant to growth inhibition by excess Dph5 levels. As judged from site-specific mutagenesis, the amidation reaction itself relies on a conserved ATP binding domain in Dph6 that, when altered, blocks diphthamide formation and confers resistance to eEF2 inhibition by sordarin.

  2. Immunity to Diphtheria and Tetanus in HIV-Infected Children

    Directory of Open Access Journals (Sweden)

    A.P. Volokha

    2017-01-01

    (0.22 IU/ml compared to the children not infected with HIV (0.43 IU/ml, p < 0001. Only 18.6 % of children in the study group were protected against both pathogens compared with 41.2 % of children in the control group. HIV-infected children are not immune to diphtheria and tetanus and are at risk of these infections. Conclusions. The main predictor of immune protection against diphtheria and tetanus is an early treatment of HIV infection (in the first 2 years of life, higher levels of CD4 + T-cells at the beginning of ART and ART vaccination after being started on ART. We recommend controlling the level of specific antibodies HIV-infected children who have received vaccination against diphtheria and tetanus before the ART beginning. In case of the absence of protective antibodies an extra booster against these bacterial infections is recommended to HIV-infected children.

  3. Silencing of cryptic prophages in Corynebacterium glutamicum.

    Science.gov (United States)

    Pfeifer, Eugen; Hünnefeld, Max; Popa, Ovidiu; Polen, Tino; Kohlheyer, Dietrich; Baumgart, Meike; Frunzke, Julia

    2016-12-01

    DNA of viral origin represents a ubiquitous element of bacterial genomes. Its integration into host regulatory circuits is a pivotal driver of microbial evolution but requires the stringent regulation of phage gene activity. In this study, we describe the nucleoid-associated protein CgpS, which represents an essential protein functioning as a xenogeneic silencer in the Gram-positive Corynebacterium glutamicum CgpS is encoded by the cryptic prophage CGP3 of the C. glutamicum strain ATCC 13032 and was first identified by DNA affinity chromatography using an early phage promoter of CGP3. Genome-wide profiling of CgpS binding using chromatin affinity purification and sequencing (ChAP-Seq) revealed its association with AT-rich DNA elements, including the entire CGP3 prophage region (187 kbp), as well as several other elements acquired by horizontal gene transfer. Countersilencing of CgpS resulted in a significantly increased induction frequency of the CGP3 prophage. In contrast, a strain lacking the CGP3 prophage was not affected and displayed stable growth. In a bioinformatics approach, cgpS orthologs were identified primarily in actinobacterial genomes as well as several phage and prophage genomes. Sequence analysis of 618 orthologous proteins revealed a strong conservation of the secondary structure, supporting an ancient function of these xenogeneic silencers in phage-host interaction.

  4. Putrescine production by engineered Corynebacterium glutamicum.

    Science.gov (United States)

    Schneider, Jens; Wendisch, Volker F

    2010-10-01

    Here, we report the engineering of the industrially relevant Corynebacterium glutamicum for putrescine production. C. glutamicum grew well in the presence of up to 500 mM of putrescine. A reduction of the growth rate by 34% and of biomass formation by 39% was observed at 750 mM of putrescine. C. glutamicum was enabled to produce putrescine by heterologous expression of genes encoding enzymes of the arginine- and ornithine decarboxylase pathways from Escherichia coli. The results showed that the putrescine yield by recombinant C. glutamicum strains provided with the arginine-decarboxylase pathway was 40 times lower than the yield by strains provided with the ornithine decarboxylase pathway. The highest production efficiency was reached by overexpression of speC, encoding the ornithine decarboxylase from E. coli, in combination with chromosomal deletion of genes encoding the arginine repressor ArgR and the ornithine carbamoyltransferase ArgF. In shake-flask batch cultures this strain produced putrescine up to 6 g/L with a space time yield of 0.1 g/L/h. The overall product yield was about 24 mol% (0.12 g/g of glucose).

  5. Ciprofloxacin triggered glutamate production by Corynebacterium glutamicum.

    Science.gov (United States)

    Lubitz, Dorit; Wendisch, Volker F

    2016-10-07

    Corynebacterium glutamicum is a well-studied bacterium which naturally overproduces glutamate when induced by an elicitor. Glutamate production is accompanied by decreased 2-oxoglutatate dehydrogenase activity. Elicitors of glutamate production by C. glutamicum analyzed to molecular detail target the cell envelope. Ciprofloxacin, an inhibitor of bacterial DNA gyrase and topoisomerase IV, was shown to inhibit growth of C. glutamicum wild type with concomitant excretion of glutamate. Enzyme assays showed that 2-oxoglutarate dehydrogenase activity was decreased due to ciprofloxacin addition. Transcriptome analysis revealed that this inhibitor of DNA gyrase increased RNA levels of genes involved in DNA synthesis, repair and modification. Glutamate production triggered by ciprofloxacin led to glutamate titers of up to 37 ± 1 mM and a substrate specific glutamate yield of 0.13 g/g. Even in the absence of the putative glutamate exporter gene yggB, ciprofloxacin effectively triggered glutamate production. When C. glutamicum wild type was cultivated under nitrogen-limiting conditions, 2-oxoglutarate rather than glutamate was produced as consequence of exposure to ciprofloxacin. Recombinant C. glutamicum strains overproducing lysine, arginine, ornithine, and putrescine, respectively, secreted glutamate instead of the desired amino acid when exposed to ciprofloxacin. Ciprofloxacin induced DNA synthesis and repair genes, reduced 2-oxoglutarate dehydrogenase activity and elicited glutamate production by C. glutamicum. Production of 2-oxoglutarate could be triggered by ciprofloxacin under nitrogen-limiting conditions.

  6. Mapping the membrane proteome of Corynebacterium glutamicum.

    Science.gov (United States)

    Schluesener, Daniela; Fischer, Frank; Kruip, Jochen; Rögner, Matthias; Poetsch, Ansgar

    2005-04-01

    In order to avoid the specific problems with intrinsic membrane proteins in proteome analysis, a new procedure was developed which is superior to the classical two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) method in terms of intrinsic membrane proteins. For analysis of the membrane proteome from Corynebacterium glutamicum, we replaced the first separation dimension, i.e., the isoelectric focusing step, by anion-exchange chromatography, followed by sodium dodecyl sulfate (SDS)-PAGE in the second separation dimension. Enrichment of the membrane intrinsic subproteome was achieved by washing with 2.5 M NaBr which removed more than 35% of the membrane-associated soluble proteins. For the extraction and solubilization of membrane proteins, the detergent amidosulfobetaine 14 (ASB-14) was most efficient in a detailed screening procedure and proved also suitable for chromatography. 356 gel bands were spotted, and out of 170 different identified proteins, 50 were membrane-integral. Membrane proteins with one up to 13 transmembrane helices were found. Careful analysis revealed that this new procedure covers proteins from a wide pI range (3.7-10.6) and a wide mass range of 10-120 kDa. About 50% of the identified membrane proteins belong to various functional categories like energy metabolism, transport, signal transduction, protein translocation, and proteolysis while for the others a function is not yet known, indicating the potential of the developed method for elucidation of membrane proteomes in general.

  7. [THE EFFECTIVENESS OF VACCINATION AGAINST DIPHTHERIA IN THE VORONEZH REGION].

    Science.gov (United States)

    Mamchik, N P; Gabbasova, N V; Sitnik, T N; Borisova, L S

    2015-01-01

    The purpose of the study was the assessment of the effectiveness of vaccination against diphtheria in the Voronezh region over the epidemic period of 1993-1997 and epidemiological welfare during 2010-2014. of the study: data of the official statistical reporting--forms number 1, 6, the serum level of antitoxic antibodies to diphtheria in 19319 healthy individuals were analyzed with the aid of epidemiological (descriptive and evaluative), immunological and statistical methods. During the epidemic rise of diphtheria (1993-1997) 75% of cases were amounted to the adult population of the Voronezh region, half of them--were not immunized against diphtheria. In 1993 there was begun mass vaccination of adult population, immunization coverage by 1998 reached 95%. According to seromonitoring data the share of seronegatives to diphtheria among cases examined during the period of 1995-2000 accountedfrom 11.9 to 24.9%. During the period of sporadic morbidity (1998-2007 years) among patients the 80% of cases have been vaccinated with an interval from the last inoculation of 3-5 years, which casts doubt on the effectiveness of vaccines. Since 2008 the incidence of diphtheria in the Voronezh region was not recorded. Against the background of 98% coverage of vaccination of the total population, the share of seronegatives for the last 5 years have decreased by 2.5 times and in 2014 reached the required performance. Documented inoculation indices fail to reflect the level of the actual protection against infection. In the conditions of the absence of the morbidity only serological monitoring is an objective criterion of the protectability of the population from infection.

  8. Septic arthritis in a native knee due to Corynebacterium striatum.

    Science.gov (United States)

    Molina Collada, Juan; Rico Nieto, Alicia; Díaz de Bustamante Ussia, Macarena; Balsa Criado, Alejandro

    2017-03-07

    We describe a case of septic arthritis in a native knee due to Corynebacterium striatum, gram-positive bacilli that are usually commensal organisms of skin and mucosal membranes, but are seldom implicated in native septic arthritis. An 84-year-old man with Corynebacterium striatum septic arthritis of his native left knee and no response to conventional antibiotic therapy. Thus, the patient was allowed to take dalbavancin for compassionate use, with an excellent clinical outcome. This case emphasizes de role of Corynebacterium striatum in native joint infections and highlights the importance of early detection and appropriate treatment in improving the clinical outcome. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  9. Corynebacterium spp. in dogs and cats with otitis externa and/or media: a retrospective study.

    Science.gov (United States)

    Henneveld, Kerstin; Rosychuk, Rodney A W; Olea-Popelka, Francisco J; Hyatt, Doreene R; Zabel, Sonja

    2012-01-01

    The role of Corynebacterium spp. in the pathogenesis of canine and feline otitis externa/media and their appropriate antimicrobial therapy are unclear. The objectives of this study were to (1) better establish the pathogenicity of Corynebacterium spp. in otitis utilizing reported criteria and by assessing clinical response to antibiotic therapy and (2) to determine the antimicrobial susceptibility patterns of Corynebacterium spp. associated with otitis. The study was retrospective, targeting cultures positive for Corynebacterium spp. Corynebacterium spp. were part of mixed microbial populations in 79/81 cultures. Corynebacterium spp. pathogenicity was highly questionable because of their almost invariable presence with other microbes and the observation that Corynebacterium spp. usually disappear from the ear with resolution of other infections, even when the Corynebacterium spp. are resistant to the prescribed antibiotic(s). However, 2/81 cultures came from two canine ears wherein Corynebacterium spp. may have been pathogenic. Antimicrobial sensitivities for Corynebacterium spp. were available for 54 isolates. Most isolates were susceptible to chloramphenicol (53/54), amikacin (50/54), tetracycline (50/54), gentamicin (46/54), and enrofloxacin (32/54). Among those antibiotics available in otic products, gentamicin and enrofloxacin would be rational choices for the empirical, topical therapy of Corynebacterium spp.

  10. Formation of volutin granules in Corynebacterium glutamicum.

    Science.gov (United States)

    Pallerla, Srinivas Reddy; Knebel, Sandra; Polen, Tino; Klauth, Peter; Hollender, Juliane; Wendisch, Volker F; Schoberth, Siegfried M

    2005-02-01

    Volutin granules are intracellular storages of complexed inorganic polyphosphate (poly P). Histochemical staining procedures differentiate between pathogenic corynebacteria such as Corynebacterum diphtheriae (containing volutin) and non-pathogenic species, such as C. glutamicum. Here we report that strains ATCC13032 and MH20-22B of the non-pathogenic C. glutamicum also formed subcellular entities (18-37% of the total cell volume) that had the typical characteristics of volutin granules: (i) volutin staining, (ii) green UV fluorescence when stained with 4',6-diamidino-2-phenylindole, (iii) electron-dense and rich in phosphorus when determined with transmission electron microscopy and X-ray microanalysis, and (iv) 31P NMR poly P resonances of isolated granules dissolved in EDTA. MgCl2 addition to the growth medium stimulated granule formation but did not effect expression of genes involved in poly P metabolism. Granular volutin fractions from lysed cells contained polyphosphate glucokinase as detected by SDS-PAGE/MALDI-TOF, indicating that this poly P metabolizing enzyme is present also in intact poly P granules. The results suggest that formation of volutin is a more widespread phenomenon than generally accepted.

  11. Your Child's Immunizations: Diphtheria, Tetanus & Pertussis Vaccine (DTaP)

    Science.gov (United States)

    ... Feeding Your 1- to 2-Year-Old Your Child's Immunizations: Diphtheria, Tetanus & Pertussis Vaccine (DTaP) KidsHealth > For Parents > ... child outweigh the potential risks. Caring for Your Child After Immunization Your child may have a fever, soreness, and ...

  12. Vaccination against tetanus, diphtheria, pertussis and poliomyelitis in adult travellers.

    Science.gov (United States)

    Gautret, Philippe; Wilder-Smith, Annelies

    2010-05-01

    This paper reviews the risk and vaccine recommendations for tetanus, diphtheria, pertussis and poliomyelitis for adult travellers. The travel clinic presents a unique opportunity to evaluate whether routine vaccinations are up-to-date. Tetanus, diphtheria and pertussis occur worldwide but are more common in low resource countries due to incomplete childhood vaccination coverage, environmental and socio-economic factors. Diphtheria has been reported in travellers without adequate protection. A booster against tetanus and diphtheria is recommended for all adult travellers, regardless of travel destination and duration. The incidence of pertussis in general adult travellers has been poorly studied. Extrapolating from the reported high incidence in travellers to the Hajj, the risk may be more substantial than thought. There are no universal recommendations for pertussis vaccination for adult travellers, and studies are needed to develop evidence based guidelines. Poliomyelitis is well controlled and now only occurs in a small number of countries. Travellers to and from endemic and re-infected countries should be fully vaccinated against poliomyelitis.

  13. Tetanus and diphtheria immunity in refugees in Europe in 2015.

    Science.gov (United States)

    Jablonka, Alexandra; Behrens, Georg M N; Stange, Marcus; Dopfer, Christian; Grote, Ulrike; Hansen, Gesine; Schmidt, Reinhold Ernst; Happle, Christine

    2017-04-01

    Current political crises in the Middle East and economic discrepancies led millions of people to leave their home countries and to flee to Western Europe. This development raises unexpected challenges for receiving health care systems. Although pan-European initiatives strive for updated and optimized vaccination strategies, little data on immunity against vaccine-preventable diseases in the current refugee population exist. We quantified serum IgG against tetanus and diphtheria (TD) in n = 678 refugees currently seeking shelter in six German refugee centers. Reflecting current migration statistics in Europe, the median age within the cohort was 26 years, with only 23.9 % of female subjects. Insufficient IgG levels without long-term protection against tetanus were found in 56.3 % of all refugees. 76.1 % of refugees had no long-term protection against diphtheria. 47.7 % of subjects needed immediate vaccination against tetanus, and 47.7 % against diphtheria. For both diseases, an age-dependent decline in protective immunity occurred. We observed a considerably low rate of tetanus-protected refugees, and the frequency of diphtheria-immune refugees was far from sufficient to provide herd immunity. These findings strongly support recent intentions to implement and enforce stringent guidelines for refugee vaccination in the current crisis.

  14. Persistence of Diphtheria, Hyderabad, India, 2003–2006

    Science.gov (United States)

    Bitragunta, Sailaja; Murhekar, Manoj V.; Hutin, Yvan J.; Penumur, Padmanabha P.

    2008-01-01

    During 2003–2006, diphtheria rates in Hyderabad, India, were higher among persons 5–19 years of age, women, and Muslims than among other groups. Vaccine was efficacious among those who received >4 doses. The proportion of the population receiving boosters was low, especially among Muslims. We recommend increasing booster dose coverage. PMID:18598644

  15. [Development studies of lyophilized standard diphtheria-tetanus-pertussis vaccines].

    Science.gov (United States)

    Ozcengiz, Erkan; Unver, Derya; Cayan, H Hüseyin; Atakan Ablay, Pinar; Kanik, Esin

    2007-04-01

    In this study, diphtheria, tetanus and pertussis vaccine components were prepared as the formulations of diphtheria-tetanus-pertussis (DTP), diphtheria-tetanus (DT) for children, diphtheria-tetanus (Td) for adults, and tetanus toxoid (TT), respectively. Alhydrogel-adsorbed vaccines prepared to contain the stabilizing substances were lyophilized and the immunogenicity tests were carried out both in vivo and in vitro. The potencies of the tetanus component of the vaccines were obtained by the lethal challenge test in mice. The values were found as 144.86 IU/ml for lyophilized adsorbed (LA)-DTP, 116.5 IU/ml for LA-DT, 98.25 IU/ml for LA-Td and 96.2 IU/ml for LA-TT. Anti-tetanus IgG and anti-diphteria IgG levels determined by ELISA method were found high in the sera taken from the mice immunized with the above-mentioned vaccines. Anti-B.pertussis fimbria IgG antibody levels were also high by both ELISA and microagglutination tests. The test preparations were then compared to adsorbed liquid vaccines and it was shown that the components were quite stable in the lyophilized formulations. It was concluded that the formulations prepared in this study can be used as standard vaccines after being calibrated against World Health Organization standards.

  16. Experimental transmission of Corynebacterium pseudotuberculosis in horses by house flies

    Science.gov (United States)

    The route of infection of pigeon fever remains undetermined. The purpose of this study was to investigate house flies (Musca domestica L.) as vectors of Corynebacterium pseudotuberculosis in horses. Eight ponies were used in a randomized, controlled, blinded experimental study. Ten wounds were creat...

  17. Native valve endocarditis due to Corynebacterium group JK.

    Science.gov (United States)

    Moffie, B G; Veenendaal, R A; Thompson, J

    1990-12-01

    We report a case of a 32-yr-old woman on chronic intermittent haemodialysis, who developed endocarditis due to a Corynebacterium group JK, involving both the native aortic and mitral valves. Despite a four-week treatment with vancomycin, an aortic root abscess developed. The diagnosis was confirmed on autopsy.

  18. Early prosthetic valve endocarditis caused by Corynebacterium kroppenstedtii.

    Science.gov (United States)

    Hagemann, Jürgen Benjamin; Essig, Andreas; Herrmann, Manuel; Liebold, Andreas; Quader, Mohamed Abo

    2015-12-01

    Corynebacterium (C.) kroppenstedtii is a rarely detected agent of bacterial infections in humans. Here, we describe the first case of prosthetic valve endocarditis caused by C. kroppenstedtii. Application of molecular methods using surgically excised valve tissue was a cornerstone for the establishment of the microbiological diagnosis, which is crucial for targeted antimicrobial treatment.

  19. Primary vaccination of adults with reduced antigen-content diphtheria-tetanus-acellular pertussis or dTpa-inactivated poliovirus vaccines compared to diphtheria-tetanus-toxoid vaccines.

    NARCIS (Netherlands)

    Theeten, H.; Rumke, H.C.; Hoppener, F.J.; Vilatimo, R.; Narejos, S.; Damme, P. van; Hoet, B.

    2007-01-01

    OBJECTIVE: To evaluate immunogenicity and reactogenicity of primary vaccination with reduced-antigen-content diphtheria-tetanus-acellular pertussis (dTpa) or dTpa-inactivated poliovirus (dTpa-IPV) vaccine compared to diphtheria-tetanus-toxoid vaccines (Td) in adults > or = 40 years of age without

  20. Primary vaccination of adults with reduced antigen-content diphtheria-tetanus-acellular pertussis or dTpa-inactivated poliovirus vaccines compared to diphtheria-tetanus-toxoid vaccines.

    NARCIS (Netherlands)

    Theeten, H.; Rumke, H.C.; Hoppener, F.J.; Vilatimo, R.; Narejos, S.; Damme, P. van; Hoet, B.

    2007-01-01

    OBJECTIVE: To evaluate immunogenicity and reactogenicity of primary vaccination with reduced-antigen-content diphtheria-tetanus-acellular pertussis (dTpa) or dTpa-inactivated poliovirus (dTpa-IPV) vaccine compared to diphtheria-tetanus-toxoid vaccines (Td) in adults > or = 40 years of age without

  1. [Diphtheria in the military forces: lessons and current status of prophylaxis, prospects of epidemiological control process].

    Science.gov (United States)

    Belov, A B; Ogarkov, P I

    2014-01-01

    We analyzed the epidemiological situation of diphtheria in the world and in Russia and experience of mass vaccination of military personnel and civil population with diphtheria toxoid for the last 50 years. Early diagnosis of diphtheria in military personnel has a prognostic value. Authors described the peculiarities of epidemiological process of diphtheria in military personnel in 80-90 years of 20th century and organizational aspects of mass vaccination with diphtheria toxoid. Authors analyzed current problems of epidemiology and prophylaxis of diphtheria in military personnel and civil population and possible developments. According to long-term prognosis authors mentioned the increase of morbidity and came to conclusion that it is necessary enhance the epidemiological surveillance. Authors presented prospect ways of improvement of vaccination and rational approaches to immunization of military personnel under positive long-term epidemiological situation.

  2. Immunity to diphtheria and tetanus among blood donors in Arak, central province of Iran.

    OpenAIRE

    Ali Eslamifar; Amitis Ramezani; Mohammad Banifazl; Masoomeh Sofian; Fatemeh-Alsadat Mahdaviani; Farhad Yaghmaie; Arezoo Aghakhani

    2014-01-01

    Background and Objectives Tetanus and diphtheria are vaccine-preventable, infectious diseases with significant morbidity and mortality. Immunization by the diphtheria and tetanus toxoid (DT) has been applied in Iran for almost 50 years. However, there are very few data about the rate of immunity to these diseases in the adult population. the humoral immunity to tetanus and diphtheria among blood donors in Arak city, central provice of Iran were investigated. Patients & Methods A total of 530 ...

  3. Tetanus and diphtheria immunity in adolescents from São Paulo, Brazil

    OpenAIRE

    M.I.S Dinelli; Fisberg, M.; de Moraes-Pinto, M. I.

    2007-01-01

    Tetanus and diphtheria vaccines are of special concern in adolescents because boosters are necessary for adequate maintenance of protection and are often omitted. We assessed serum levels of tetanus and diphtheria antibodies in adolescents and their association with vaccination status. From May to October 2001, we evaluated the vaccination records of 208 adolescents aged 10 to 20 years in São Paulo, Brazil. Antibodies to tetanus and diphtheria were detected using double-antigen ELISA and vacc...

  4. A Case-control Study of Diphtheria in the High Incidence City of Hyderabad, India.

    Science.gov (United States)

    Allam, Ramesh Reddy; Uthappa, Chengappa Kechamada; Duerst, Rebecca; Sorley, Evan; Udaragudi, Prasada Rao; Kampa, Shankar; Dworkin, Mark S

    2016-03-01

    India accounts for approximately 72% of reported diphtheria cases globally, the majority of which occur in the state of Andhra Pradesh. The aim of this study is to better understand lack of knowledge on diphtheria vaccination and to determine factors associated with diphtheria and low knowledge and negative attitudes. We performed a 1:1 case-control study of hospitalized diphtheria cases in Hyderabad. Eligible case patients were 10 years of age or older, resided within the city of Hyderabad and were diagnosed with diphtheria per the case definition. Patients admitted to the hospital for nonrespiratory communicable diseases and residing in the same geographic region as that of cases were eligible for enrolment as controls : There were no statistical differences in disease outcome by gender, education, economic status and mean room per person sleeping in the house in case and control subjects. Not having heard of diphtheria (adjusted odds ratio: 3.56; 95% confidence intervals: 1.58-8.04] and not believing that vaccines can prevent people from getting diseases (adjusted odds ratio: 3.99; 95% confidence intervals: 1.18-13.45) remained significantly associated with diphtheria on multivariate analysis. To reduce the burden of diphtheria in India, further efforts to educate the public about diphtheria should be considered.

  5. Access to diphtheria antitoxin for therapy and diagnostics.

    Science.gov (United States)

    Both, L; White, J; Mandal, S; Efstratiou, A

    2014-06-19

    The most effective treatment for diphtheria is swift administration of diphtheria antitoxin (DAT) with conjunct antibiotic therapy. DAT is an equine immunoglobulin preparation and listed among the World Health Organization Essential Medicines. Essential Medicines should be available in functioning health systems at all times in adequate amounts, in appropriate dosage forms, with assured quality, and at prices individuals and the community can afford. However, DAT is in scarce supply and frequently unavailable to patients because of discontinued production in several countries, low economic viability, and high regulatory requirements for the safe manufacture of blood-derived products. DAT is also a cornerstone of diphtheria diagnostics but several diagnostic reference laboratories across the European Union (EU) and elsewhere routinely face problems in sourcing DAT for toxigenicity testing. Overall, global access to DAT for both therapeutic and diagnostic applications seems inadequate. Therefore--besides efforts to improve the current supply of DAT--accelerated research and development of alternatives including monoclonal antibodies for therapy and molecular-based methods for diagnostics are required. Given the rarity of the disease, it would be useful to organise a small stockpile centrally for all EU countries and to maintain an inventory of DAT availability within and between countries.

  6. [Significant bacteremias by Corynebacterium amycolatum: an emergent pathogen].

    Science.gov (United States)

    Oteo, J; Aracil, B; Ignacio Alós, J; Luis Gómez-Garcés, J

    2001-03-01

    Corynebacterium sp. is an extremely varied genus which includes little known species and of which only Corynebacterium diphteriae, Corynebacterium urealyticum and Corynebacterium jeikeium are considered indisputable pathogens. Other species, such as C. amycolatum are at present being reconsidered as causative agents in infectious pathologies, partly on account of our greater aquaintance and improved identification techniques for these microorganisms and partly on account of the growing number of immunocompromised patients in whom all their pathogenic capacity is usually able to develope. We present 3 cases of significant bacteremia by C. amycolatum. Bacterial isoliations from blood culture were obtained using the Vital Systems. Identification was performed by means of Gran stain, colony morphology, the results of numerous biochemical tests (including the Api Coryne systems), the behaviour of the strains against the vibriostatic agent O/129 and the antibiotic susceptibility pattern obtained with the E-test. The three isolates of C. amycolatum were obtained from patients after a lenghtly hospitalization, multi-instrumentation and who had severe underlying disease. All three presented with concomitant isolates of C. amycolatum from other sites: sputum, wound and catheter respectively, which could explain the origin of the bacteremia. Colony morphology, antibiotic susceptibility patterns, resistance to the vibriostatic agent O/129 and the results of the biochemical test carried out were similar to those previously describe in the literature. C. amycolatum should be born in mind as a agent responsable for significant and severe pathology in this type of patient. In addition, it as certain specific characteristics which assits in its identification in the normal micr

  7. Histidine biosynthesis, its regulation and biotechnological application in Corynebacterium glutamicum

    OpenAIRE

    Kulis-Horn, Robert K; Persicke, Marcus; Kalinowski, Jörn

    2013-01-01

    l-Histidine biosynthesis is an ancient metabolic pathway present in bacteria, archaea, lower eukaryotes, and plants. For decades l-histidine biosynthesis has been studied mainly in Escherichia coli and Salmonella typhimurium, revealing fundamental regulatory processes in bacteria. Furthermore, in the last 15 years this pathway has been also investigated intensively in the industrial amino acid-producing bacterium Corynebacterium glutamicum, revealing similarities to E. coli and S. typhimurium...

  8. Corynebacterium glutamicum Metabolic Engineering with CRISPR Interference (CRISPRi)

    OpenAIRE

    Cleto, Sara; Jensen, Jaide VK; Wendisch, Volker F; Lu, Timothy K.

    2016-01-01

    Corynebacterium glutamicum is an important organism for the industrial production of amino acids. Metabolic pathways in this organism are usually engineered by conventional methods such as homologous recombination, which depends on rare double-crossover events. To facilitate the mapping of gene expression levels to metabolic outputs, we applied CRISPR interference (CRISPRi) technology using deactivated Cas9 (dCas9) to repress genes in C. glutamicum. We then determined the effects of target re...

  9. Quantitative aspects of fecal Rhodococcus (Corynebacterium) equi in foals.

    OpenAIRE

    Takai, S.; Ohkura, H; Watanabe, Y.; Tsubaki, S

    1986-01-01

    Quantitative aspects of fecal Rhodococcus (Corynebacterium) equi in newborn foals for 12 weeks after birth were investigated on two horse breeding farms. R. equi was found in the feces of foals during week 1 of life. The greatest numbers of R. equi were present in the feces of foals during the first 8 weeks of their lives, which coincides with the age when foals are most liable to be exposed to R. equi.

  10. Complete Genome Sequence of Corynebacterium pseudotuberculosis Viscerotropic Strain N1

    Science.gov (United States)

    Portela, Ricardo W.; Sousa, Thiago J.; Rocha, Flávia; Pereira, Felipe L.; Dorella, Fernanda A.; Carvalho, Alex F.; Menezes, Nildo; Macedo, Eduardo S.; Moura-Costa, Lilia F.; Meyer, Roberto; Leal, Carlos A. G.; Figueiredo, Henrique C.; Azevedo, Vasco

    2016-01-01

    We present the complete genome sequence of Corynebacterium pseudotuberculosis strain N1. The sequencing was performed with the Ion Torrent Personal Genome Machine system. The genome is a circular chromosome with 2,337,845 bp, a G+C content of 52.85%, and a total of 2,045 coding sequences, 12 rRNAs, 49 tRNAs, and 58 pseudogenes. PMID:26823597

  11. Corynebacterium propinquum: A Rare Cause of Prosthetic Valve Endocarditis

    Directory of Open Access Journals (Sweden)

    Umair Jangda

    2016-01-01

    Full Text Available Nondiphtheria Corynebacterium species are often dismissed as culture contaminants, but they have recently become increasingly recognized as pathologic organisms. We present the case of a 48-year-old male patient on chronic prednisone therapy for rheumatoid arthritis with a history of mitral valve replacement with prosthetic valve. He presented with fever, dizziness, dyspnea on exertion, intermittent chest pain, and palpitations. Transesophageal echocardiography revealed two medium-sized densities along the inner aspect of the sewing ring and one larger density along the atrial surface of the sewing ring consistent with vegetation. Two separate blood cultures grew Corynebacterium propinquum, which were sensitive to ceftriaxone but highly resistant to vancomycin and daptomycin. The patient completed a course of ceftriaxone and repeat TEE study and after 6 weeks demonstrated near complete resolution of the vegetation. To our knowledge, this case represents the first in the literature of Corynebacterium propinquum causing prosthetic valve endocarditis. The ability of these organisms to cause deep-seated systemic infections should be recognized, especially in immune-compromised patients.

  12. Seroprevalence of diphtheria toxoid IgG antibodies in children, adolescents and adults in Poland.

    Science.gov (United States)

    Zasada, Aleksandra A; Rastawicki, Waldemar; Rokosz, Natalia; Jagielski, Marek

    2013-11-19

    Recommendations for diphtheria immunization are to apply an effective primary immunization in infancy and to maintain immunity throughout life. Immunity against diphtheria depends primarily on antibody to the diphtheria toxin. This study evaluated the seroprevalence of IgG diphtheria antitoxin in sera of healthy children, adolescents and adults in Poland. A total of 1387 serum samples collected between 2010 and 2012 from individuals with ages ranging from 1 month to 85 years were investigated. Antibody concentrations were measured with an enzyme-linked immunosorbent assay (Anti-Diphtheria Toxoid ELISA IgG, Euroimmun, Germany). The results showed that among 1387 individuals examined, 547 (39.4%) had anti-diphtheria toxoid IgG antibody levels below 0.1 IU/ml (36.9% ≤ 18 years and 40.5% >18 years old, respectively). The 212 (50.8%) children and 542 (55.9%) adults showed only basic protection (0.1-1.0 IU/ml) and need immediate booster. High levels of anti-diphtheria toxoid IgG antibodies (>1.0 IU/ml) were found more often in children and adolescent (12.2%) than in adults (3.6%) and this was statistically significant (P 60 years old. Characteristically, in individuals > 40 years old high levels of anti-diphtheria toxoid IgG antibodies (>1.0 IU/ml) were not seen. There were no statistically significant differences in results in relation to gender. The present study showed inadequate immunity levels to diphtheria amongst the Polish population, especially in adults > 40 years old and children ≤ 2 years old. To prevent reemergence of diphtheria an information campaign reminding people about recommendations concerning diphtheria booster vaccination in adults should be conducted. Moreover, the immunogenicity of the DTP vaccine used in Poland should be verified.

  13. THE ACCELERATED METHOD FOR IDENTIFICATION OF PATHOGENIC CORYNEBACTERIUM

    OpenAIRE

    2013-01-01

    Abstract. The detection of cystinase activity is one of most important tests in the laboratory diagnosis of diphtheria, giving the opportunity to differentiate potential toxigenic species from other coryneform bacteria. The original recipe of Pizu media for detection of cystinase activity, proposed in 1939–1940, was modified several times (1982, 1989) for different reasons. In the last modification the Pizu media was prepared by using the AGV media as a nutritional base. We suggest a modifica...

  14. THE ACCELERATED METHOD FOR IDENTIFICATION OF PATHOGENIC CORYNEBACTERIUM

    Directory of Open Access Journals (Sweden)

    S. A. Gabrielyan

    2013-01-01

    Full Text Available Abstract. The detection of cystinase activity is one of most important tests in the laboratory diagnosis of diphtheria, giving the opportunity to differentiate potential toxigenic species from other coryneform bacteria. The original recipe of Pizu media for detection of cystinase activity, proposed in 1939–1940, was modified several times (1982, 1989 for different reasons. In the last modification the Pizu media was prepared by using the AGV media as a nutritional base. We suggest a modification of Pizu media using Mueller-Hinton agar as nutritional basis. The Mueller-Hinton agar has a number of advantages: higher nutritional value, standardization, transparency and availability. A positive result is defined within 2–4 hours after inoculation of enough quantity of material (pure culture or C. diphtheriaе in association with other microorganisms as a brown halo surrounding black colonies. The brown halo does not appear in the upper part of the media (0,5–1 cm. The modified media was checked with 21 strains of C. diphtheriaе (tox+, nine strains of coryneform bacteria, control strains NCTC 10648, NCTC 10356, NCTC 3984. The modified Pizu media is registered in the RA mental property agency as an invention (no. 1877 A2, 15.12.2006.

  15. Comparison of a multiplex flow cytometric assay with enzyme-linked immunosorbent assay for auantitation of antibodies to tetanus, diphtheria, and Haemophilus influenzae Type b.

    Science.gov (United States)

    Pickering, Jerry W; Martins, Thomas B; Schroder, M Carl; Hill, Harry R

    2002-07-01

    We developed a multiplexed indirect immunofluorescence assay for antibodies to Haemophilus influenza type b (Hib) polysaccharide and the toxoids of Clostridium tetani (Tet) and Corynebacterium diphtheriae (Dip) based on the Luminex multiple-analyte profiling system. A pooled serum standard was calibrated against World Health Organization standards for Dip and Tet and an international standard for Hib. The multiplexed Luminex assay was compared to individual enzyme-linked immunosorbent assays (ELISAs) for the same analytes. By both methods, 75 (92.6%) of 81 of random serum samples had protective levels of antibody to Tet (> or = 0.1 IU/ml). For Dip, 81.5% of the samples had protective antibody levels (> or = 0.1 IU/ml) by ELISA and 80.2% had protective antibody levels by Luminex. Protective levels (> or = 1.0 microg/ml) of antibody to Hib were found in 45.0% of the samples tested by ELISA and in 39.0% of the samples tested by Luminex. The correlations (R(2)) between ELISA and Luminex of the 81 samples were 0.96, 0.96, and 0.91 for Tet, Dip, and Hib, respectively. There was also similar agreement between Luminex and ELISA for sera collected before and 1 month after Tet, Dip, and Hib vaccine administration. Both methods detected strong postvaccination responses. The Luminex method is an attractive alternative to ELISA since it reduces labor and reagent costs, as well as assay time.

  16. Solution 1H NMR characterization of substrate-free C. diphtheriae heme oxygenase: pertinence for determining magnetic axes in paramagnetic substrate complexes.

    Science.gov (United States)

    Du, Zhenming; Unno, Masaki; Matsui, Toshitaka; Ikeda-Saito, Masao; La Mar, Gerd N

    2010-10-01

    Proton 2D NMR was used to confirm in solution a highly conserved portion of the molecular structure upon substrate loss for the heme oxygenase from the pathogenic bacterium Corynebacterium diphtheriae, HmuO. The chemical shifts for the conserved portion of the structure are assessed as references for the dipolar shifts needed to determine the orientation of the paramagnetic susceptibility tensor, chi, in paramagnetic substrate complexes of HmuO. It is shown that the chemical shifts for the structurally conserved portion of substrate-free HmuO serve as excellent references for residues with only small to moderate sized dipolar shifts in the cyanide-inhibited substrate complex of HmuO, yielding an orientation of chi that is essentially the same as conventionally obtained from large dipolar shifts based on empirical estimates of the diamagnetic reference. The implications of these diamagnetic chemical shifts for characterizing the hydrogen bonding in the physiologically relevant, resting-state, high-spin aquo complex are discussed. The pattern of labile proton exchange in the distal H-bond network of substrate-free HmuO allowed comparison of changes in dynamic stability of tertiary contacts in the substrate-free and substrate-bound HmuO and with the same complexes of human heme oxygenase.

  17. THE RETURN OF THE STRANGLER? CASE REPORT OF A FATAL CASE OF DIPHTHERIA

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    Srikamakhsi Kothandaraman

    2012-11-01

    Full Text Available This article is a case report of a case of diphtheria which presented as diphtheritic tonsillitis in stridor and finallysuccumbed to diphtheritic myocarditis. Here we describe the case presentation, the treatment modalities undertaken,and the fatal course of events followed by an elaborate discussion on diphtheria.

  18. Structural perturbation of diphtheria toxoid upon adsorption to aluminium hydroxide adjuvant

    NARCIS (Netherlands)

    Regnier, Marie; Metz, Bernard; Tilstra, Wichard; Hendriksen, Coenraad; Jiskoot, Wim; Norde, Willem; Kersten, Gideon

    2012-01-01

    Aluminium-containing adjuvants are often used to enhance the potency of vaccines. In the present work we studied whether adsorption of diphtheria toxoid to colloidal aluminium hydroxide induces conformational changes of the antigen. Diphtheria toxoid has a high affinity for the aluminium hydroxide p

  19. Seroprevalence study of anti diphtheria antibodies in two age-groups of Romanian adults.

    Science.gov (United States)

    Dragomirescu, Cristiana Cerasella; Coldea, Ileana-Luminiţa; Ilie, Anamaria; Stănescu, Aurora; Ungureanu, Vasilica; Popa, Mircea Ioan

    2014-01-01

    Diphtheria represents a serious infectious disease with high epidemic potential. It is a vaccine preventable disease (a minimum vaccine coverage of 95% for children of 1 year and 90% in adults could prevent the disease). Diphtheria vaccination is included in the National Immunization Program (NIP). Complete vaccination for children consists in DTaP (diphtheria toxoid, tetanus toxoid and acellular pertussis vaccine) vaccine administration from the age of 2 months until 4 years and dT vaccine (tetanus toxoid and a reduced dose of diphtheria toxoid) at 14 years old. The aim of this paper was to highlight the protection against diphtheria of an age segment of the Romanian adult population (20 to 39 years old) using a seroprevalence study. The Romanian subjects were selected from two age groups: 20-29 years (n = 219) and 30-39 years (n = 229), representative for all counties of Romania. The commercial kit Anti-Diphtheria Toxoid ELISA (IgG) (EUROIMMUN) was used to detect the antibodies of IgG class against diphtheria toxoid in the sera obtained from our subjects. We detected a 56.6% rate of positive sera (> 0.1 IU/ml--protection level) for the 20-29 age group and 31.7% positivity for the 30-39 age group. These data show a low protection level against diphtheria of the Romanian adult population, which decreases with age. The serologic data on preventable vaccine diseases are useful in order to evaluate the success of the immunization programs.

  20. The period of recover and outcomes of the diphtheria at adults (kliniko-statistical research

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    Yu. P. Finogeev

    2010-01-01

    Full Text Available In 1824 a man sick with diphtheria during an epidemic of this infection in the mid nineties of the last century complications registered at an average of 16,17%. When combined diphtheria complications were observed in 58,78%, with only the defeat of the pharynx – in 12,78%. Multiple organ lesions in diphtheria are protected from one year to seven years. We observed patients mortality was on average 2,24%. The lowest mortality was in diphtheria throat – 0,66%, with a combined form of the disease – 22,14%. It is advisable to revise the terms of active surveillance recover this infection. The leading cause of death in diphtheria was infection-toxic shock syndrome is often associated with infection – toxic myocarditis.

  1. Baseline immunity to diphtheria and immunologic response after booster vaccination with reduced diphtheria and tetanus toxoid vaccine in Thai health care workers.

    Science.gov (United States)

    Wiboonchutikul, Surasak; Manosuthi, Weerawat; Sangsajja, Chariya; Thientong, Varaporn; Likanonsakul, Sirirat; Srisopha, Somkid; Termvises, Patamavadee; Rujitip, Jitlada; Loiusirirotchanakul, Suda; Puthavathana, Pilaipan

    2014-07-01

    A prospective study to evaluate immune status against diphtheria and immunologic response after tetanus-diphtheria (Td) booster vaccination was conducted in 250 Thai health care workers (HCWs). A protective antibody was found in 89.2% of the HCWs (95% confidence interval [CI], 83.3%-91.5%) before receipt of the Td booster vaccination, compared with 97.2% (95% CI, 95.1%-99.3%) after receipt of the first dose of booster (P diphtheria increased from 0.39 IU/mL (95% CI, 0.35-0.44 IU/mL) before the Td booster vaccination to 1.20 IU/mL (95% CI, 1.12-1.29 IU/mL) after the vaccination (P vaccination should be considered for Thai HCWs to maintain immunity against diphtheria, which still circulates in Thailand.

  2. Re-emergence of diphtheria and pertussis: implications for Nigeria.

    Science.gov (United States)

    Sadoh, A E; Oladokun, R E

    2012-11-26

    In the prevaccine era pertussis and diphtheria were responsible for significant morbidity and mortality in children. In the United States of America more than 125,000 cases of diphtheria with 10,000 deaths were reported annually in the 1920s. In the same period about 1.7 million cases of pertussis with 73,000 deaths were also reported. Vaccination against these two diseases has caused remarkable reduction in the morbidity and mortality from these diseases both in developed and developing countries. The initial vaccines were the combined diphtheria toxoid and whole cell pertussis vaccine. The recent reported increases in the incidence of these two diseases in countries, which maintain high childhood vaccination coverage is a source of concern not only to these countries but also for developing countries with weak immunization programmes. Nigeria for example reported 11,281 cases of pertussis, the second highest number of cases worldwide in 2009. Waning immunity in adult and adolescent populations has been reported and epidemiologically, more cases are being reported in adults and adolescents. Also a high proportion of pertussis cases are being reported in infants and most of these infant cases are linked to adult/adolescent sources. Recent approaches to control of these diseases include booster doses of combined diphtheria, tetanus and acellular pertussis vaccine while the cocooning strategy (which is immunizing every person who is likely to have contact with a given infant such as mother, father, grandparents and health care workers) is being used in a number of countries. For developing countries including Nigeria where the capacity for making the diagnosis of both diseases is limited, strengthening of routine immunization as well as diagnostic capacity is imperative. Research to determine current levels of immunity in children, adolescents and adults is required. This will enable the determination of the need for booster doses and the age at which such boosters

  3. Disruption of Plasmodium sporozoite transmission by depletion of sporozoite invasion-associated protein 1.

    Science.gov (United States)

    Engelmann, Sabine; Silvie, Olivier; Matuschewski, Kai

    2009-04-01

    Accumulation of infectious Plasmodium sporozoites in Anopheles spp. salivary glands marks the final step of the complex development of the malaria parasite in the insect vector. Sporozoites are formed inside midgut-associated oocysts and actively egress into the mosquito hemocoel. Traversal of the salivary gland acinar cells correlates with the sporozoite's capacity to perform continuous gliding motility. Here, we characterized the cellular role of the Plasmodium berghei sporozoite invasion-associated protein 1 (SIAP-1). Intriguingly, SIAP-1 orthologs are found exclusively in apicomplexan hemoprotozoa, parasites that are transmitted by arthropod vectors, e.g., Plasmodium, Babesia, and Theileria species. By fluorescent tagging with mCherry, we show that SIAP-1 is expressed in oocyst-derived and salivary gland-associated sporozoites, where it accumulates at the apical tip. Targeted disruption of SIAP-1 does not affect sporozoite formation but causes a partial defect in sporozoite egress from oocysts and abolishes sporozoite colonization of mosquito salivary glands. Parasites with the siap-1(-) mutation are blocked in their capacity to perform continuous gliding motility. We propose that arthropod-transmitted apicomplexan parasites specifically express secretory factors, such as SIAP-1, that mediate efficient oocyst exit and migration to the salivary glands.

  4. Disruption of Plasmodium Sporozoite Transmission by Depletion of Sporozoite Invasion-Associated Protein 1▿ §

    Science.gov (United States)

    Engelmann, Sabine; Silvie, Olivier; Matuschewski, Kai

    2009-01-01

    Accumulation of infectious Plasmodium sporozoites in Anopheles spp. salivary glands marks the final step of the complex development of the malaria parasite in the insect vector. Sporozoites are formed inside midgut-associated oocysts and actively egress into the mosquito hemocoel. Traversal of the salivary gland acinar cells correlates with the sporozoite's capacity to perform continuous gliding motility. Here, we characterized the cellular role of the Plasmodium berghei sporozoite invasion-associated protein 1 (SIAP-1). Intriguingly, SIAP-1 orthologs are found exclusively in apicomplexan hemoprotozoa, parasites that are transmitted by arthropod vectors, e.g., Plasmodium, Babesia, and Theileria species. By fluorescent tagging with mCherry, we show that SIAP-1 is expressed in oocyst-derived and salivary gland-associated sporozoites, where it accumulates at the apical tip. Targeted disruption of SIAP-1 does not affect sporozoite formation but causes a partial defect in sporozoite egress from oocysts and abolishes sporozoite colonization of mosquito salivary glands. Parasites with the siap-1(−) mutation are blocked in their capacity to perform continuous gliding motility. We propose that arthropod-transmitted apicomplexan parasites specifically express secretory factors, such as SIAP-1, that mediate efficient oocyst exit and migration to the salivary glands. PMID:19181869

  5. Structure modeling of a metalloendopeptidase from Corynebacterium pseudotuberculosis.

    Science.gov (United States)

    Guimarães, Luis C; Silva, Natália F; Miyoshi, Anderson; Schneider, Maria P C; Silva, Artur; Azevedo, Vasco; Brasil, Davi S B; Lameira, Jerônimo; Alves, Cláudio N

    2012-05-01

    Metalloendopeptidases are zinc-dependent hydrolases enzymes with many different roles in biological systems, ranging from remodeling conjunctive tissue to removing signaling sequences from nascent proteins. Here, we describe the three-dimensional structure of the metalloendopeptidase from Corynebacterium pseudotuberculosis generated by homology modeling and molecular dynamics. Analysis of key distances shows that His-132, Asp-136, His-211, Leu-212 and one molecule of water play an important role in the protein-Zn(2+) ion interaction. The model obtained may provide structural insights into this enzyme and can be useful for the design of new caseous lymphadenitis vaccines based on genetic attenuation from key point mutation.

  6. Vaginitis Caused by Corynebacterium amycolatum in a Prepubescent Girl.

    Science.gov (United States)

    Chen, Xiao; Zhao, Xiaofeng; Chen, Lifeng; Zeng, Wenjie; Xu, Haiou

    2015-12-01

    Vaginal discharge is the most common gynecological symptom in prepubescent girls. We report a case of vaginitis caused by Corynebacterium amycolatum in a prepubescent girl and successful treatment with targeted antibiotics. Vaginal discharge is most commonly attributed to poor hygiene or nonspecific irritants; however, some patients have recurrent vulvovaginitis that is primarily caused by a variety of bacteria. For these patients, identifying the associated pathogens is critical for treatment. Copyright © 2015 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  7. Mucosal vaccination against diphtheria using starch microparticles as adjuvant for cross-reacting material (CRM197) of diphtheria toxin.

    Science.gov (United States)

    Rydell, Niclas; Sjöholm, Ingvar

    2005-04-15

    Mucosal vaccination has the advantage of eliciting a local mucosal immune response as well as a systemic response. In this investigation, polyacryl starch microparticles were conjugated to diphtheria toxin cross-reacting material (CRM197) as a mucosal adjuvant for oral or intranasal immunisation of mice. Various methods of stabilising CRM197 with formaldehyde were investigated. A good systemic and local mucosal immune response was attained with oral immunisation when CRM197 was treated with a relatively low formaldehyde concentration prior to conjugation to the microparticles. No immune response was seen after intranasal immunisation.

  8. Cardiac involvement in diphtheria: Study from a tertiary referral infectious disease hospital

    Directory of Open Access Journals (Sweden)

    Alakes Kumar Kole

    2012-01-01

    Full Text Available Background: Diphtheria is still a fatal disease even in the era of universal immunization. Diphtheria myocarditis, one of the serious complications of respiratory diphtheria may cause death if not recognized and treated properly. Aims and Objectives: To determine the outcomes of cardiac involvement in respiratory diphtheria. Materials and Methods: One hundred (n = 100 patients with respiratory tract diphtheria were evaluated in respect to cardiac involvement. All patients were closely monitored for a minimum period of 4-6 weeks from the onset of respiratory symptoms. Continuous ECG monitoring including blood biochemistry (SGOT, CPK-MB, and Troponin-T were done in each case. Results : The most common symptoms were throat pain seen in 94 cases, palpitation in 56 cases, bull neck in 40 cases, shortness of breath in 12 cases, fever in 9 cases, and nasal regurgitation in 8 cases. Most common complication observed was myocarditis seen in 70 patients and majority of patients (60 were asymptomatic. The ECG changes were T wave inversion in 54 patients, inappropriate sinus tachycardia in 38 patients, ST segment depression in precordial leads in 8 patients, Mobitz type II block in 6 patients, Mobitz type I block in 4 patients, RBBB in 4 patients, multiple atrial ectopics in 4 patients, and sinus bradycardia in 2 patients. A total number of five patients died. Conclusions: Myocarditis was commonest and serious complication of respiratory diphtheria. Increase in vaccination coverage and improvement of socioeconomic status are all effective preventive measures to reduce the incidence of diphtheria.

  9. Diphtheria in the Dominican Republic: reduction of cases following a large outbreak.

    Science.gov (United States)

    Garib, Zacarías; Danovaro-Holliday, M Carolina; Tavarez, Yira; Leal, Irene; Pedreira, Cristina

    2015-10-01

    To describe the most recent outbreak of diphtheria in the Dominican Republic and the disease's occurrence and vaccination coverage in 2004-2013. Clinical data of diphtheria cases that occurred in 2004 and that met the study's case definition were reviewed along with socioeconomic and epidemiological information from the cases' families. Univariate and multivariate analyses were performed to assess risk factors for fatal diphtheria. Routine surveillance and vaccination coverage data are presented. From January 2004-April 2005, a total of 145 diphtheria cases were reported; 80 (66%) of the 122 cases reported in 2004 met the case definition; 26 were fatal (case-fatality rate: 32.5%). Incidence was highest in the group 1-4 years of age at 5.3 per 100 000; 62.5% were male. Of the 80 cases, 61 (76%) where hospitalized in Hospital A, 17 in Hospital B, and 2 in two other hospitals. Earlier onset (first half of 2004), birth order, and tracheotomy were associated with fatal diphtheria (P diphtheria incidence was 4.91 cases/1 million people in 2000-2003, climbed to 8.8 cases per million in 2004-2005, and dropped to 0.38 in 2006-2014; no diphtheria cases have been reported since 2011. DTP3 vaccination coverage ranged from 72%-81% in 2000-2004 and from 81%-89% in 2005-2013. The 2004-2005 diphtheria outbreak in the Dominican Republic resulted in important and avoidable morbidity and mortality. Annual cases declined and no cases have been reported in recent years. Maintaining high vaccination coverage and diligent surveillance are crucial to preventing diphtheria outbreaks and controlling the disease.

  10. A microbiological and clinical review on Corynebacterium kroppenstedtii

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    Andreas Tauch

    2016-07-01

    Full Text Available The genus Corynebacterium represents a taxon of Gram-positive bacteria with a high G + C content in the genomic DNA. Corynebacterium kroppenstedtii is an unusual member of this taxon as it lacks the characteristic mycolic acids in the cell envelope. Genome sequence analysis of the C. kroppenstedtii type strain has revealed a lipophilic (lipid-requiring lifestyle and a remarkable repertoire of carbohydrate uptake and utilization systems. Clinical isolates of C. kroppenstedtii have been obtained almost exclusively from female patients and mainly from breast abscesses and cases of granulomatous mastitis. However, the role of C. kroppenstedtii in breast pathologies remains unclear. This review provides a comprehensive overview of the taxonomy, microbiology, and microbiological identification of C. kroppenstedtii, including polyphasic phenotypic approaches, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and the use of 16S rRNA gene sequencing. A clinical review presents reported cases, various antimicrobial treatments, antibiotic susceptibility assays, and antibiotic resistance genes detected during genome sequencing. C. kroppenstedtii must be considered a potential opportunistic human pathogen and should be identified accurately in clinical laboratories.

  11. Functional characterization of a vanillin dehydrogenase in Corynebacterium glutamicum.

    Science.gov (United States)

    Ding, Wei; Si, Meiru; Zhang, Weipeng; Zhang, Yaoling; Chen, Can; Zhang, Lei; Lu, Zhiqiang; Chen, Shaolin; Shen, Xihui

    2015-01-27

    Vanillin dehydrogenase (VDH) is a crucial enzyme involved in the degradation of lignin-derived aromatic compounds. Herein, the VDH from Corynebacterium glutamicum was characterized. The relative molecular mass (Mr) determined by SDS-PAGE was ~51 kDa, whereas the apparent native Mr values revealed by gel filtration chromatography were 49.5, 92.3, 159.0 and 199.2 kDa, indicating the presence of dimeric, trimeric and tetrameric forms. Moreover, the enzyme showed its highest level of activity toward vanillin at pH 7.0 and 30°C, and interestingly, it could utilize NAD(+) and NADP(+) as coenzymes with similar efficiency and showed no obvious difference toward NAD(+) and NADP(+). In addition to vanillin, this enzyme exhibited catalytic activity toward a broad range of substrates, including p-hydroxybenzaldehyde, 3,4-dihydroxybenzaldehyde, o-phthaldialdehyde, cinnamaldehyde, syringaldehyde and benzaldehyde. Conserved catalytic residues or putative cofactor interactive sites were identified based on sequence alignment and comparison with previous studies, and the function of selected residues were verified by site-directed mutagenesis analysis. Finally, the vdh deletion mutant partially lost its ability to grow on vanillin, indicating the presence of alternative VDH(s) in Corynebacterium glutamicum. Taken together, this study contributes to understanding the VDH diversity from bacteria and the aromatic metabolism pathways in C. glutamicum.

  12. Preventing tetanus, diphtheria, and pertussis among adolescents: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccines recommendations of the Advisory Committee on Immunization Practices (ACIP).

    Science.gov (United States)

    Broder, Karen R; Cortese, Margaret M; Iskander, John K; Kretsinger, Katrina; Slade, Barbara A; Brown, Kristin H; Mijalski, Christina M; Tiwari, Tejpratap; Weston, Emily J; Cohn, Amanda C; Srivastava, Pamela U; Moran, John S; Schwartz, Benjamin; Murphy, Trudy V

    2006-03-24

    During spring 2005, two tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (Tdap) products formulated for use in adolescents (and, for one product, use in adults) were licensed in the United States (BOOSTRIX, GlaxoSmithKline Biologicals, Rixensart, Belgium [licensed May 3, 2005, for use in persons aged 10-18 years], and ADACEL, sanofi pasteur, Toronto, Ontario, Canada [licensed June 10, 2005, for use in persons aged 11-64 years]). Prelicensure studies demonstrated safety and efficacy against tetanus, diphtheria, and pertussis when Tdap was administered as a single booster dose to adolescents. To reduce pertussis morbidity in adolescents and maintain the standard of care for tetanus and diphtheria protection, the Advisory Committee on Immunization Practices (ACIP) recommends that: 1) adolescents aged 11-18 years should receive a single dose of Tdap instead of tetanus and diphtheria toxoids vaccine (Td) for booster immunization against tetanus, diphtheria, and pertussis if they have completed the recommended childhood diphtheria and tetanus toxoids and whole cell pertussis vaccine (DTP)/ diphtheria and tetanus toxoids and acellular pertussis vaccine (DTaP) vaccination series (five doses of pediatric DTP/DTaP before the seventh birthday; if the fourth dose was administered on or after the fourth birthday, the fifth dose is not needed) and have not received Td or Tdap. The preferred age for Tdap vaccination is 11-12 years; 2) adolescents aged 11-18 years who received Td, but not Tdap, are encouraged to receive a single dose of Tdap to provide protection against pertussis if they have completed the recommended childhood DTP/DTaP vaccination series. An interval of at least 5 years between Td and Tdap is encouraged to reduce the risk for local and systemic reactions after Tdap vaccination. However, an interval less than 5 years between Td and Tdap can be used; and 3) vaccine providers should administer Tdap and tetravalent meningococcal conjugate

  13. The diphtheria vaccine debacle of 1940 that ushered in comprehensive childhood immunization in the United Kingdom.

    Science.gov (United States)

    Mortimer, P P

    2011-04-01

    In January 1940 British Ministry of Health circular 1307 proposed the introduction of mass childhood diphtheria immunization. This was a policy reversal after a decade during which opportunities for diphtheria prophylaxis were ignored, or resisted on grounds of cost. Diphtheria toxoid was to be the first of many centrally funded childhood immunizations in the UK and it set a pattern that has now held good for over 70 years. The circumstances in 1940 were particularly fortuitous, and diphtheria toxoid has since given successive generations of children a lifetime's protection from the disease; but difficulties have been experienced in introducing and evaluating some of the more recent immunizations, and in maintaining and justifying them in the face of parental scepticism and academic or pressure-group opposition, however ill-founded this may have been. The task of decision-making with regard to new candidate vaccines demands a careful balancing against the costs of the expected benefits during the recipient's lifespan.

  14. [State of immunity to diphtheria and tetanus in women in early postpartum period].

    Science.gov (United States)

    Savis'ko, A A; Kostinov, M P; Kharseeva, G G; Labushkina, A V; Alutina, É L

    2011-01-01

    Study of anti-diphtheria and anti-tetanus immunity in women in early postpartum period depending on age. Women in early postpartum period (n =139) with unknown vaccine anamnesis aged 17 to 44 years and under the supervision of Rostov-on-Don maternity hospital No. 2 were examined for the evaluation of the anti-diphtheria and anti-tetanus immunity state. All the women had high level of protection form these infections. The level of anti-tetanus immunity intensity in the examined was higher than anti-diphtheria. Monitoring of anti-diphtheria and anti-tetanus immunity in women of childbearing age is necessary to resolve the issue of vaccine administration in this group. High level of maternal immunity intensity will allow to form a sufficient protection from infectious agents in neonates.

  15. The WHO Review of the Possible Nonspecific Effects of Diphtheria-Tetanus-Pertussis Vaccine

    DEFF Research Database (Denmark)

    Aaby, Peter; Ravn, Henrik; Benn, Christine S

    2016-01-01

    BACKGROUND: World Health Organization recently reviewed the possible nonspecific effects of diphtheria-tetanus-pertussis (DTP) vaccine. The results were considered inconsistent though most studies suggested deleterious effects. We examined whether inconsistencies in results reflected differences...

  16. Tetanus and diphtheria antibodies and response to a booster dose in Brazilian HIV-1-infected women.

    Science.gov (United States)

    Bonetti, Tatiana C S; Succi, Regina C M; Weckx, Lily Y; Tavares-Lopes, L; de Moraes-Pinto, M Isabel

    2004-09-09

    Tetanus and diphtheria (Td) antibodies were studied in HIV-1-infected women during puerperium. HIV group (n=61) was compared with Control group (n=101). Twenty-one women from HIV and 13 from Control group who had antibody levels lower than 0.1 IU/mL received a booster with Td vaccine. Antibodies were assessed by double antigen ELISA. Mean tetanus and diphtheria antibody levels from HIV group were lower than those from Control group. Multiple linear regression analysis showed that tetanus and diphtheria antibody levels were decreased by HIV-1-infection, and that was independent of the reduction due to the time interval between last booster and antibody assessment. After a booster dose, both groups had an increase in mean tetanus and diphtheria antibody levels, but in Control group the levels were higher than in HIV group.

  17. Short-term booster effect of diphtheria toxoid in initially long-term protected individuals.

    Science.gov (United States)

    Danilova, Elena; Shiryayev, Alexey; Skogen, Vegard; Kristoffersen, Einar Klaeboe; Sjursen, Haakon

    2005-02-10

    The main objective of this study was to investigate the booster antibody response in individuals with initially high levels of diphtheria antitoxin. Sixty individuals eligible for the routine booster by the age of 18 years each received a single dose of 5 Lf of diphtheria toxoid in diphtheria-tetanus vaccine. A double antigen ELISA was used for the assessment of the antibody levels. Chaotropic disruption in paired ELISA was used to test antibody avidity. The ratio between initial and maximum antibody concentrations after 1 month was >10 times higher and after 6 months still four times higher in those with initial antibody levels antibody levels >/=1 IU/ml a two-fold decrease was observed after 6 months compared to the initial levels. Thus, vaccination of individuals with initial long-term protection against diphtheria (antibody levels >/=1 IU/ml) is unnecessary and should be avoided.

  18. Complete genome sequence of Corynebacterium pseudotuberculosis Cp31, isolated from an Egyptian buffalo

    DEFF Research Database (Denmark)

    Silva, Artur; Ramos, Rommel Thiago Jucá; Ribeiro Carneiro, Adriana

    2012-01-01

    Corynebacterium pseudotuberculosis is of major veterinary importance because it affects many animal species, causing economically significant livestock diseases and losses. Therefore, the genomic sequencing of various lines of this organism, isolated from different hosts, will aid in the developm...

  19. Experimental transmission of Corynebacterium pseudotuberculosis biovar equi in horses by house flies

    Science.gov (United States)

    The route of Corynebacterium pseudotuberculosis infection in horses remains undetermined, but transmission by insects is suspected. Scientists from CMAVE and Auburn University investigated house flies (Musca domestica L.) as possible vectors. Three ponies were directly inoculated with C. pseudotuber...

  20. Tetanus and diphtheria immunity in adolescents from São Paulo, Brazil

    Directory of Open Access Journals (Sweden)

    M.I.S Dinelli

    2007-02-01

    Full Text Available Tetanus and diphtheria vaccines are of special concern in adolescents because boosters are necessary for adequate maintenance of protection and are often omitted. We assessed serum levels of tetanus and diphtheria antibodies in adolescents and their association with vaccination status. From May to October 2001, we evaluated the vaccination records of 208 adolescents aged 10 to 20 years in São Paulo, Brazil. Antibodies to tetanus and diphtheria were detected using double-antigen ELISA and vaccination records were analyzed according to the guidelines of the Brazilian National Immunization Program. All adolescents had received complete primary vaccinations against tetanus and diphtheria, but 23.1% of them had not received a booster dose in the last 10 years. All adolescents were immune to tetanus and 88.9% were fully protected (antibodies ³0.1 IU/mL. One individual (0.5% was non-immune to diphtheria and 86% were fully protected against the disease. Adolescents with up-to-date vaccination records had higher antibody levels than those with not up-to-date records for tetanus (0.763 vs 0.239 IU/mL, t-test: P < 0.0001 and diphtheria (0.366 vs 0.233 IU/mL, t-test: P = 0.014. Full immunity against tetanus (antibodies ³0.1 IU/mL was higher among individuals with up-to-date vaccination (93.1% when compared to those with not up-to-date records (75%, Fisher's exact test: P = 0.001. All adolescents had received basic immunization in childhood and were protected against tetanus and diphtheria. However, these data indicate that more emphasis should be placed on the tetanus-diphtheria booster in order to avoid a decay in antibody levels.

  1. Tetanus and diphtheria immunity in adolescents from São Paulo, Brazil.

    Science.gov (United States)

    Dinelli, M I S; Fisberg, M; de Moraes-Pinto, M I

    2007-02-01

    Tetanus and diphtheria vaccines are of special concern in adolescents because boosters are necessary for adequate maintenance of protection and are often omitted. We assessed serum levels of tetanus and diphtheria antibodies in adolescents and their association with vaccination status. From May to October 2001, we evaluated the vaccination records of 208 adolescents aged 10 to 20 years in São Paulo, Brazil. Antibodies to tetanus and diphtheria were detected using double-antigen ELISA and vaccination records were analyzed according to the guidelines of the Brazilian National Immunization Program. All adolescents had received complete primary vaccinations against tetanus and diphtheria, but 23.1% of them had not received a booster dose in the last 10 years. All adolescents were immune to tetanus and 88.9% were fully protected (antibodies (3)0.1 IU/mL). One individual (0.5%) was non-immune to diphtheria and 86% were fully protected against the disease. Adolescents with up-to-date vaccination records had higher antibody levels than those with not up-to-date records for tetanus (0.763 vs 0.239 IU/mL, t-test: P diphtheria (0.366 vs 0.233 IU/mL, t-test: P = 0.014). Full immunity against tetanus (antibodies (3)0.1 IU/mL) was higher among individuals with up-to-date vaccination (93.1%) when compared to those with not up-to-date records (75%, Fisher's exact test: P = 0.001). All adolescents had received basic immunization in childhood and were protected against tetanus and diphtheria. However, these data indicate that more emphasis should be placed on the tetanus-diphtheria booster in order to avoid a decay in antibody levels.

  2. Tetanus and diphtheria immunity in adolescents from São Paulo, Brazil

    Directory of Open Access Journals (Sweden)

    M.I.S Dinelli

    Full Text Available Tetanus and diphtheria vaccines are of special concern in adolescents because boosters are necessary for adequate maintenance of protection and are often omitted. We assessed serum levels of tetanus and diphtheria antibodies in adolescents and their association with vaccination status. From May to October 2001, we evaluated the vaccination records of 208 adolescents aged 10 to 20 years in São Paulo, Brazil. Antibodies to tetanus and diphtheria were detected using double-antigen ELISA and vaccination records were analyzed according to the guidelines of the Brazilian National Immunization Program. All adolescents had received complete primary vaccinations against tetanus and diphtheria, but 23.1% of them had not received a booster dose in the last 10 years. All adolescents were immune to tetanus and 88.9% were fully protected (antibodies ³0.1 IU/mL. One individual (0.5% was non-immune to diphtheria and 86% were fully protected against the disease. Adolescents with up-to-date vaccination records had higher antibody levels than those with not up-to-date records for tetanus (0.763 vs 0.239 IU/mL, t-test: P < 0.0001 and diphtheria (0.366 vs 0.233 IU/mL, t-test: P = 0.014. Full immunity against tetanus (antibodies ³0.1 IU/mL was higher among individuals with up-to-date vaccination (93.1% when compared to those with not up-to-date records (75%, Fisher's exact test: P = 0.001. All adolescents had received basic immunization in childhood and were protected against tetanus and diphtheria. However, these data indicate that more emphasis should be placed on the tetanus-diphtheria booster in order to avoid a decay in antibody levels.

  3. The problem of the periodicity of the epidemic process. [solar activity effects on diphtheria outbreak

    Science.gov (United States)

    Yagodinskiy, V. N.; Konovalenko, Z. P.; Druzhinin, I. P.

    1974-01-01

    An analysis of data from epidemics makes it possible to determine their principal causes, governed by environmental factors (solar activity, etc.) The results of an analysis of the periodicity of the epidemic process in the case of diphtheria are presented which was conducted with the aid of autocorrelation and spectral methods of analysis. Numerical data (annual figures) are used on the dynamics of diphtheria in 50 regions (points) with a total duration of 2,777 years.

  4. Isolation and Characterization of a Black-Pigmented Corynebacterium sp. from a Woman with Spontaneous Abortion

    OpenAIRE

    Shukla, Sanjay K.; Vevea, Dirk N.; Daniel N Frank; Pace, Norman R.; Reed, Kurt D.

    2001-01-01

    An unusual black-pigmented coryneform bacterium was isolated from the urogenital tract of a woman who experienced a spontaneous abortion during month 6 of pregnancy. Biochemical and chemotaxonomic analyses demonstrated that the unknown bacterium belonged to the genus Corynebacterium. Phylogenetic analysis based on 16S rRNA sequences (GenBank accession no. AF220220) revealed that the organism was a member of a distinct subline which includes uncultured Corynebacterium MTcory 1P (GenBank access...

  5. Compliance with diphtheria, tetanus, and pertussis immunisation in Bangladesh

    DEFF Research Database (Denmark)

    Zeitlyn, S; Rahman, A K; Nielsen, B H

    1992-01-01

    of immunisation, and she was given clear instructions to bring the child back after four weeks for the second dose. MAIN OUTCOME MEASURE: Rate of non-compliance with advice to return child for second vaccination. RESULTS: 46 of 113 children (41%) received the second dose of the vaccine. Factors most closely......OBJECTIVE: To evaluate factors associated with non-compliance with having second vaccination against diphtheria, tetanus, and pertussis in a treatment centre in Dhaka to determine which children were most at risk of not completing immunisation. DESIGN: Cohort study of infants given first dose...... of the vaccine and followed up six weeks later to ascertain compliance with having second dose. Factors associated with non-compliance were evaluated. SETTING: Dhaka treatment centre of the International Centre for Diarrhoeal Disease Research, Bangladesh. SUBJECTS: 136 unimmunised children aged 6 weeks to 23...

  6. Epidemiology and control of diphtheria in the Republic of Moldova, 1946-1996.

    Science.gov (United States)

    Magdei, M; Melnic, A; Benes, O; Bukova, V; Chicu, V; Sohotski, V; Bass, A

    2000-02-01

    In 1994-1996, the Republic of Moldova was stricken with an epidemic of diphtheria after >30 years of routine diphtheria immunization and the near absence of the disease for nearly 20 years. The intensity of the epidemic gradually grew, reaching a peak in 1994-1995. The epidemiology of diphtheria in Moldova during this period is described along with laboratory findings and control measures. Pharyngeal diphtheria was the predominant clinical form of the disease (97% of cases), and it most often developed in a localized form (70%), with 20% in the toxic form. The clinical diagnosis of diphtheria was bacteriologically confirmed in 91% of cases: Of the cases tested for biotype, 91.3% were gravis, 8.5% were mitis, and 0. 2% were intermedius. Of 494 toxigenic isolates from cases and carriers at the beginning of the epidemic, 47% were nonphagotypeable strains, and 25.7% were phagotype VI strains. Aggressive population-based diphtheria control measures, a mass immunization campaign, rapid case identification, antibiotic prophylaxis and supplemental immunization of close contacts in clusters of infection, and high coverage with routine immunization rapidly controlled the epidemic within Moldova.

  7. 白喉毒素突变体CRM197在白喉杆菌中的表达纯化%Expression and Purification of the Diphtheria Toxin Variant CRM197 in Corynebacterium diphtheriae

    Institute of Scientific and Technical Information of China (English)

    朱涛; 邓立功; 段磊; 常云松; 邵忠琦; 毛慧华; 宇学峰

    2014-01-01

    CRM197是一种白喉毒素突变体,第52位的甘氨酸突变为谷氨酸,作为载体蛋白广泛用于疫苗开发.将阐述一种新的生产CRM197方法.将合成的CRM197基因片段克隆到表达载体pCKM4.1中,表达质粒pCKM5.1电转化至大肠杆菌E.coliS17-1中,通过结合转移转化至白喉杆菌(ATCC(R) 27010TM的白喉杆菌)中,载体上的导肽序列可以使得CRM197作为可溶性蛋白分泌到胞外表达,CRM197蛋白可占到菌体总蛋白的70%.增强对铁的调控,进一步优化培养基及发酵条件以提高产量.经过Q膜、硫酸铵沉淀、阴离子交换纯化步骤获得纯度达到95%的CRM197样品,提高了蛋白得率,节约了纯化时间和成本.

  8. [Influence of genetic and phenotypical factors on the efficiency of the vaccination of young children against diphtheria and measles].

    Science.gov (United States)

    Gordeeva, L A; Shabaldin, A V; Semenova, E M; Glushkov, A N

    2006-01-01

    The child's sex was shown to influence the character of antibody formation only after immunization against diphtheria with live measles vaccine: girls exhibited stronger reaction to vaccination than boys. Children of different gender were found to have characteristic HLA DR markers of humoral immune response to diphtheria toxoid and measles vaccine. HLA DR7 proved to be the marker of low production of antibodies to diphtheria toxoid and measles vaccine in boys.

  9. Outbreak of Corynebacterium pseudodiphtheriticum infection in cystic fibrosis patients, France.

    Science.gov (United States)

    Bittar, Fadi; Cassagne, Carole; Bosdure, Emmanuelle; Stremler, Nathalie; Dubus, Jean Christophe; Sarles, Jacques; Reynaud-Gaubert, Martine; Raoult, Didier; Rolain, Jean-Marc

    2010-08-01

    An increasing body of evidence indicates that nondiphtheria corynebacteria may be responsible for respiratory tract infections. We report an outbreak of Corynebacterium pseudodiphtheriticum infection in children with cystic fibrosis (CF). To identify 18 C. pseudodiphtheriticum strains isolated from 13 French children with CF, we used molecular methods (partial rpoB gene sequencing) and matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry. Clinical symptoms were exhibited by 10 children (76.9%), including cough, rhinitis, and lung exacerbations. The results of MALDI-TOF identification matched perfectly with those obtained from molecular identification. Retrospective analysis of sputum specimens by using specific real-time PCR showed that approximately 20% of children with CF were colonized with these bacteria, whereas children who did not have CF had negative test results. Our study reemphasizes the conclusion that correctly identifying bacteria at the species level facilitates detection of an outbreak of new or emerging infections in humans.

  10. Corynebacterium glutamicum Metabolic Engineering with CRISPR Interference (CRISPRi).

    Science.gov (United States)

    Cleto, Sara; Jensen, Jaide Vk; Wendisch, Volker F; Lu, Timothy K

    2016-05-20

    Corynebacterium glutamicum is an important organism for the industrial production of amino acids. Metabolic pathways in this organism are usually engineered by conventional methods such as homologous recombination, which depends on rare double-crossover events. To facilitate the mapping of gene expression levels to metabolic outputs, we applied CRISPR interference (CRISPRi) technology using deactivated Cas9 (dCas9) to repress genes in C. glutamicum. We then determined the effects of target repression on amino acid titers. Single-guide RNAs directing dCas9 to specific targets reduced expression of pgi and pck up to 98%, and of pyk up to 97%, resulting in titer enhancement ratios of l-lysine and l-glutamate production comparable to levels achieved by gene deletion. This approach for C. glutamicum metabolic engineering, which only requires 3 days, indicates that CRISPRi can be used for quick and efficient metabolic pathway remodeling without the need for gene deletions or mutations and subsequent selection.

  11. Diphtheria toxin treatment of Pet-1-Cre floxed diphtheria toxin receptor mice disrupts thermoregulation without affecting respiratory chemoreception

    Science.gov (United States)

    Cerpa, Verónica; Gonzalez, Amalia; Richerson, George B.

    2014-01-01

    In genetically-modified Lmx1bf/f/p mice, selective deletion of LMX1B in Pet-1 expressing cells leads to failure of embryonic development of serotonin (5-HT) neurons. As adults, these mice have a decreased hypercapnic ventilatory response and abnormal thermoregulation. This mouse model has been valuable in defining the normal role of 5-HT neurons, but it is possible that developmental compensation reduces the severity of observed deficits. Here we studied mice genetically modified to express diphtheria toxin receptors (DTR) on Pet-1 expressing neurons (Pet-1-Cre/Floxed DTR or Pet1/DTR mice). These mice developed with a normal complement of 5-HT neurons. As adults, systemic treatment with 2 – 35 μg diphtheria toxin (DT) reduced the number of tryptophan hydroxylase immunoreactive (TpOH-ir) neurons in the raphe nuclei and ventrolateral medulla by 80%. There were no effects of DT on baseline ventilation (VE) or the ventilatory response to hypercapnia or hypoxia. At an ambient temperature (TA) of 24°C, all Pet1/DTR mice dropped their body temperature (TB) below 35°C after DT treatment, but the latency was shorter in males than females (3.0 ± 0.37 vs 4.57 ± 0.29 days, respectively; p thermoregulation, in males more than females. In comparison to models with deficient embryonic development of 5-HT neurons, acute deletion of 5-HT neurons in adults leads to a greater defect in thermoregulation, suggesting that significant developmental compensation can occur. PMID:25171790

  12. Effect of cell wall deficiency on Tox gene of Corynebacterium diphtheriae%细胞壁缺陷对白喉棒状杆菌Tox基因影响

    Institute of Scientific and Technical Information of China (English)

    易旭; 王和

    2006-01-01

    目的 探讨细胞壁缺陷对白喉棒状杆菌毒力基因及其表达的影响.方法 以非高渗分离培养法诱导并获得产毒性白喉棒状杆菌稳定L型纯培养物,提取白喉棒状杆菌稳定L型的染色体DNA,用Tox基因特异性引物进行PCR扩增,并进行序列测定和分析.分别采用对流免疫电泳(CIEP)和十二烷基磺酸钠-不连续聚丙烯酰胺凝胶电泳(SDS-PAGE)检测白喉棒状杆菌稳定L型可溶性代谢产物中的白喉毒素蛋白质.结果 白喉棒状杆菌在氨苄青霉素作用下可发生细胞壁缺陷而成为L型,该稳定L型的传代培养物可仍然保留同其亲代细菌型一致的Tox基因及其核苷酸序列;但在其可溶性代谢产物中并未检测到白喉毒素蛋白质.结论 白喉棒状杆菌稳定L型虽然保留了Tox基因但并不能表达白喉毒素蛋白质,提示细胞壁缺陷可影响Tox基因在宿主菌细胞内的表达.

  13. Transcutaneous immunization with cross-reacting material CRM(197) of diphtheria toxin boosts functional antibody levels in mice primed parenterally with adsorbed diphtheria toxoid vaccine.

    Science.gov (United States)

    Stickings, Paul; Peyre, Marisa; Coombes, Laura; Muller, Sylviane; Rappuoli, Rino; Del Giudice, Giuseppe; Partidos, Charalambos D; Sesardic, Dorothea

    2008-04-01

    Transcutaneous immunization (TCI) capitalizes on the accessibility and immunocompetence of the skin, elicits protective immunity, simplifies vaccine delivery, and may be particularly advantageous when frequent boosting is required. In this study we examined the potential of TCI to boost preexisting immune responses to diphtheria in mice. The cross-reacting material (CRM(197)) of diphtheria toxin was used as the boosting antigen and was administered alone or together with either one of two commonly used mucosal adjuvants, cholera toxin (CT) and a partially detoxified mutant of heat-labile enterotoxin of Escherichia coli (LTR72). We report that TCI with CRM(197) significantly boosted preexisting immune responses elicited after parenteral priming with aluminum hydroxide-adsorbed diphtheria toxoid (DTxd) vaccine. In the presence of LTR72 as an adjuvant, toxin-neutralizing antibody titers were significantly higher than those elicited by CRM(197) alone and were comparable to the functional antibody levels induced after parenteral booster immunization with the adsorbed DTxd vaccine. Time course study showed that high levels of toxin-neutralizing antibodies persisted for at least 14 weeks after the transcutaneous boost. In addition, TCI resulted in a vigorous antigen-specific proliferative response in all groups of mice boosted with the CRM(197) protein. These findings highlight the promising prospect of using booster administrations of CRM(197) via the transcutaneous route to establish good herd immunity against diphtheria.

  14. [The return of diphtheria in Europe. Is the French population protected?].

    Science.gov (United States)

    Rey, M; Vincent-Ballereau, F; Patey, O

    1997-01-01

    Following the generalized vaccination of children, the European countries achieved the elimination of diphtheria. However the huge epidemic which rages since 1990 in the New Independent States of ex-URSS, culminating in 1994-1995 (with respectively 47,802 and 50,412 notified cases), has showed that diphtheria could be still threatening. A serosurvey was carried out in France on 1,025 adult patients attending the emergency wards of three hospitals, located in different parts of this country. This study showed the insufficient immunity of adults, for lack of a routine programme for revaccination: only half of them have antibodies assuring their protection. The antitoxic immunity decreases according to age. This decline is more marked in women than in men, most of them being reimmunized during the military service. These data confirm the alarming results of similar serosurveys performed in others industrialized countries. The present risk of importing diphtheria in these countries requires a strengthening of clinical and bacteriological surveillance of all cases of infections attributable to C. diphtheriae, and could justify a revaccination programme for adult population, including a regular booster, at 10 year-interval, of a reduced dose of diphtheria toxoid (d), and/or using the combined toxoid Td in the wounded, instead of tetanus toxoid alone.

  15. Immunity to Diphtheria and Tetanus in Army Personnel and Adult Civilians in Mashhad, Iran.

    Science.gov (United States)

    Hosseini Shokouh, Seyyed Javad; Mohammadi, Babak; Rajabi, Jalil; Mohammadian Roshan, Ghasem

    2017-03-24

    This study aimed to investigate serologic immunity to diphtheria and tetanus in army personnel and a sample population of adult civilians in Mashhad, Iran. Army personnel (n = 180) and civilians (n = 83) who presented at Mashhad army hospital participated in this study. Diphtheria and tetanus antitoxin levels were determined by enzyme-linked immunosorbent assay. Approximately 77% and 94% of army personnel aged 18-34 years had at least basic protection against diphtheria (antitoxin level ≥0.1 IU/mL) and tetanus (antitoxin level >0.1 IU/mL), respectively. For civilians in this age group, the proportions were 76% for both diseases. Antitoxin levels waned with age. Thus, participants older than 50 years had lower immunity; this decrease in immunity was more pronounced for tetanus than for diphtheria in both army personnel and civilians. For both diseases, geometric mean antitoxin titers and the proportion of participants with at least basic protection were higher in subjects with a history of vaccination in the last 10 years (P army personnel than civilians in each age group. Young army personnel and civilians (18-34 years old) had adequate immunity to diphtheria and tetanus. However, the large number of susceptible older adults (>50 years old) calls for improved booster vaccination protocols.

  16. Outcomes of respiratory diphtheria in a tertiary referral infectious disease hospital

    Directory of Open Access Journals (Sweden)

    A K Kole

    2010-01-01

    Full Text Available Background: Diphtheria is a fatal disease and may cause serious complications if not recognized early and treated properly. Objectives:To study the epidemiology, clinical features, complications, and outcomes in respiratory diphtheria. Materials and Methods:Diphtheria cases admitted in the infectious disease hospital, Beliaghata, Kolkata, India between January 2009 to January 2011 were evaluated in respect to demographic profile, immunization status, clinical features, complications, and outcomes. Results: 200 diphtheria cases were studied. 150 (75% patients had history of an adequate immunization, and 100 (50% patients were from lower socio-economic groups. Common clinical features observed were throat pain in 148 (74% cases and fever in 112 (56% cases. Complications observed were myocarditis in 136 (68% cases, neuropathy in 30 (15% cases, and respiratory compromise in 14 (7% cases. Death occurred in 5 (2.5% patients. Conclusions:diphtheria is still a public health problem in many developing countries. Strict public health measures like an increased immunization coverage, improvement of socio-economic status, easy availability of anti-diphtheritic serum (ADS, early recognition and effective treatment-all may reduce the incidence and mortality.

  17. Evaluation of human antibody responses to diphtheria toxin subunits A and B in various age groups.

    Science.gov (United States)

    Karakus, R; Caglar, K; Aybay, C

    2007-11-01

    This study aimed to evaluate human antibody responses to diphtheria toxin subunits in various age groups. Antibodies against the intact diphtheria toxin and the diphtheria toxin subunits A and B were evaluated in 1319 individuals using a double-antigen ELISA. Although high levels of protection (83.6%, 95% CI 79.2-87.4) were found in children and adolescents, the middle-aged adult population was less protected (28.8%, 95% CI 24.3-33.6). An increase in age was associated with a decrease in the frequency of protected individuals in the 0-39-year age group (p antibodies against the intact toxin. In children aged antibodies were observed were found to correlate with the ages at which booster doses are administered. Overall, males appeared to be more protected than females (OR 1.67, 95% CI 1.34-2.08, p antibody levels of > or =0.1 IU/mL against the intact toxin, but did not have protective antibody against subunit B. Determination of anti-subunit B antibody levels should help in evaluating the effectiveness of diphtheria boosters and other aspects of diphtheria immunity.

  18. Calibration and commutability assessment of the 1st International Standard for Diphtheria Antitoxin Human.

    Science.gov (United States)

    Stickings, Paul; Rigsby, Peter; Coombes, Laura; von Hunolstein, Christina; Ralli, Luisa; Pinto, Antonella; Sesardic, Dorothea

    2013-11-01

    The 1st International Standard for Diphtheria Antitoxin Human (coded 10/262) was established by the World Health Organization Expert Committee on Biological Standardization in 2012. This paper describes the production, characterization and calibration of the new standard which is intended for use in the standardization of assays used to measure diphtheria antibody responses in human serum. The new standard was calibrated in terms of the International Standard for Diphtheria Antitoxin Equine in an international collaborative study. A total of 8 participants from 8 different countries performed in vivo and/or in vitro toxin neutralization tests and returned data that was used to assign units to the proposed new standard. The new standard has a diphtheria antitoxin potency of 2 IU/ampoule and is predicted to be stable. A follow up study was performed to assess commutability of the new standard. The follow up study was an existing external quality assessment, modified to include the new standard. Results obtained suggest that the new standard is commutable, showing comparable behaviour to native human serum samples in the majority of the assays compared, and is therefore suitable for use as a reference preparation in assays used to measure the level of anti-diphtheria antibodies in human serum.

  19. Comparative evolutionary genomics of Corynebacterium with special reference to codon and amino acid usage diversities.

    Science.gov (United States)

    Pal, Shilpee; Sarkar, Indrani; Roy, Ayan; Mohapatra, Pradeep K Das; Mondal, Keshab C; Sen, Arnab

    2017-09-18

    The present study has been aimed to the comparative analysis of high GC composition containing Corynebacterium genomes and their evolutionary study by exploring codon and amino acid usage patterns. Phylogenetic study by MLSA approach, indel analysis and BLAST matrix differentiated Corynebacterium species in pathogenic and non-pathogenic clusters. Correspondence analysis on synonymous codon usage reveals that, gene length, optimal codon frequencies and tRNA abundance affect the gene expression of Corynebacterium. Most of the optimal codons as well as translationally optimal codons are C ending i.e. RNY (R-purine, N-any nucleotide base, and Y-pyrimidine) and reveal translational selection pressure on codon bias of Corynebacterium. Amino acid usage is affected by hydrophobicity, aromaticity, protein energy cost, etc. Highly expressed genes followed the cost minimization hypothesis and are less diverged at their synonymous positions of codons. Functional analysis of core genes shows significant difference in pathogenic and non-pathogenic Corynebacterium. The study reveals close relationship between non-pathogenic and opportunistic pathogenic Corynebaterium as well as between molecular evolution and survival niches of the organism.

  20. Desensitization with DTP (diphtheria, tetanus and pertussis vaccine

    Directory of Open Access Journals (Sweden)

    Atanasković-Marković Marina

    2003-01-01

    Full Text Available Immunization with DTP vaccine (diphtheria, tetanus and pertussis is a part of the vaccination calendar offered in childhood. Adverse allergic reactions vary from minimal urticarial reactions to life-threatening anaphylaxis. In infancy these reactions usually interrupt the vaccination calendar, but immunization in these children should be done. At the University Children's Hospital of Belgrade, a group of 137 children with suspected allergic anaphylactic reaction to DTP, DT, TT and monopertussis vaccine was studied for the last six years. Skin (prick and intradermal tests were performed with corresponding vaccine. If both tests were negative, the vaccine could be given as a single dose of 0.5 ml. If one of these tests were positive desensitization with vaccine could be done (according to the protocol described by Carey and Meltzer. In one group of 52 children three days before desensitization, premedication with antihistamines, was done, whereas in the other group of 52 children premedication was not done. Two (3.8% children in a group of 52 children with premedication had a minor (local reaction after vaccination and 50 children (96.2% had no reaction after vaccination, whereas no children (0% had systemic reaction after desensitization.

  1. Antibodies to tetanus, diphtheria and pertussis among healthy adults vaccinated according to the French vaccination recommendations.

    Science.gov (United States)

    Launay, Odile; Toneatti, Christine; Bernède, Claire; Njamkepo, Elisabeth; Petitprez, Karine; Leblond, Annie; Larnaudie, Sylvie; Goujon, Catherine; Ungeheuer, Marie-Noelle; Ajana, Faïza; Raccurt, Christian; Beytout, Jean; Chidiac, Christian; Bouhour, Damien; Guillemot, Didier; Guiso, Nicole

    2009-05-01

    In this sero-epidemiological study, we investigated humoral immunity to three vaccine-preventable diseases--tetanus, diphtheria and pertussis--among 331 adults (aged 18-60 years) attending vaccination centres for travellers and who had been vaccinated according to national recommendations in France. Serological results showed that the percentage of subjects with antibodies to diphtheria and tetanus decreases with age. Results also confirmed surveillance data on vaccination in France, with 7.6% of the study population (13.4% of those aged 18-29 years) having recently acquired a pertussis infection. These results confirm the importance of following French recommendations for regular boosters for tetanus and diphtheria among adults. They also indicate the need for better implementation of the current recommendations for pertussis-vaccine boosters in adults.

  2. Investigation of an Outbreak of Diphtheria in Dabela Village of Amirgagh Taluka and CHC, Banaskantha, Gujarat

    Directory of Open Access Journals (Sweden)

    Niti Talsania, Jignesh Chauhan, Himanshu Nayak, Chintul Shah, Krunal Modi, Jaydeep devaliya

    2011-01-01

    Full Text Available As outbreak of diphtheria reflects the impact of immunization outbreak investigation was carried out to assess the diphtheria outbreak pattern and case fatality rate in Dabela Village of Amirgagh Taluka and CHC, District, Banaskantha, Gujarat in 2007. Population stabilization, poverty alleviation, lifestyle modification, surveillance and control of communicable and non-communicable diseases constitute the major challenges demanding urgent attention in the future. Vaccine was efficacious among those who received >4 doses. The proportion of the population receiving boosters was low, especially among Muslims. We recommend increasing booster dose coverage. We investigated epidemic to 1 describe the epidemiology of diphtheria in terms of time, place, and person; 2 estimate vaccine coverage; and 3 to do SWOT analysis in Immunization services.4 To suggest successful vaccination.

  3. System analysis of changes in cardiovascular circulatory dynamics in experimental diphtheria in rabbit.

    Science.gov (United States)

    Zotov, A K; Frolov, V A; Zotova, T J

    2009-09-01

    Trivariate correlation analysis of hemodynamic indices of the cardiovascular system in rabbits with diphtheria showed that adaptation of this system to direct action of diphtherin can be visualized by analysis of trivariate correlation tightness for indices of intraventricular pressure in the left and right ventricles and indices of systemic blood pressure. Using empirical production functions for systemic blood pressure indices we found that the contribution of intraventricular pressure in the left and right ventricles on blood pressure values is changed in diphtheria compared to the control. Basing on entropy analysis we established that the regimen of control over values of working intraventricular pressure in both left and right ventricles in diphtheria is changed from quasidetermined to stochastic.

  4. Comparison of gel filtration and ammonium sulphate precipitation in the purification of diphtheria toxin and toxoid.

    Science.gov (United States)

    Møyner, K; Christiansen, G

    1984-02-01

    Crude diphtheria toxin and toxoid were subjected to purification by gel filtration and stepwise ammonium sulphate precipitation. The various fractions obtained by the purification procedures were studied by immunological methods. A high molecular weight fraction of glycoprotein nature was present in all of the crude preparations studied. The fraction was antigenically non-identical with the real toxin or toxoid and did not have its origin in the culture medium. It showed a long flocculation time when tested against equine diphtheria toxoid antiserum. The fraction could be removed from the crude preparations by gel filtration or by precipitation with 21% (w/v) ammonium sulphate. When comparing toxoids purified by each of these methods, the method of gel filtration resulted in a somewhat higher degree of purity, suggesting that this method would be more suitable than the AS precipitation method for the purification of diphtheria toxoid.

  5. Semicarbazone EGA Inhibits Uptake of Diphtheria Toxin into Human Cells and Protects Cells from Intoxication

    Directory of Open Access Journals (Sweden)

    Leonie Schnell

    2016-07-01

    Full Text Available Diphtheria toxin is a single-chain protein toxin that invades human cells by receptor-mediated endocytosis. In acidic endosomes, its translocation domain inserts into endosomal membranes and facilitates the transport of the catalytic domain (DTA from endosomal lumen into the host cell cytosol. Here, DTA ADP-ribosylates elongation factor 2 inhibits protein synthesis and leads to cell death. The compound 4-bromobenzaldehyde N-(2,6-dimethylphenylsemicarbazone (EGA has been previously shown to protect cells from various bacterial protein toxins which deliver their enzymatic subunits from acidic endosomes to the cytosol, including Bacillus anthracis lethal toxin and the binary clostridial actin ADP-ribosylating toxins C2, iota and Clostridium difficile binary toxin (CDT. Here, we demonstrate that EGA also protects human cells from diphtheria toxin by inhibiting the pH-dependent translocation of DTA across cell membranes. The results suggest that EGA might serve for treatment and/or prevention of the severe disease diphtheria.

  6. Chromosomally encoded small antisense RNA in Corynebacterium glutamicum.

    Science.gov (United States)

    Zemanová, Martina; Kaderábková, Pavla; Pátek, Miroslav; Knoppová, Monika; Silar, Radoslav; Nesvera, Jan

    2008-02-01

    The first observation of chromosomally encoded small antisense RNA in Corynebacterium glutamicum is reported. Transcription oriented in the reverse direction to the transcription of the genes cg1934 and cg1935 was demonstrated within the chromosomal cg1934-cg1935 intergenic region. The transcription was found to be increased after heat shock. The transcriptional start point of this RNA designated ArnA was localized 21 bp upstream of the cg1935 translational start point by primer extension analysis, when the total RNA was isolated from cells grown at 30 degrees C. After heat shock, the transcriptional start point of an additional species of ArnA RNA was detected 19 bp upstream of the cg1935 translational start point. The stress-response sigma factor SigH was found to be involved in the synthesis of ArnA RNAs. The 3' end of the ArnA RNAs was identified using the 3'-rapid amplification of cDNA ends technique. The length of the two ArnA RNA species was thus determined to be 129 and 131 nt, respectively. The ArnA RNAs were found to overlap the 5'-untranslated region of the transcript of the cg1935 gene coding for a transcriptional regulator of the GntR family. These results suggest that the noncoding ArnA RNAs have a regulatory function.

  7. Metabolic engineering for improved production of ethanol by Corynebacterium glutamicum.

    Science.gov (United States)

    Jojima, Toru; Noburyu, Ryoji; Sasaki, Miho; Tajima, Takahisa; Suda, Masako; Yukawa, Hideaki; Inui, Masayuki

    2015-02-01

    Recombinant Corynebacterium glutamicum harboring genes for pyruvate decarboxylase (pdc) and alcohol dehydrogenase (adhB) can produce ethanol under oxygen deprivation. We investigated the effects of elevating the expression levels of glycolytic genes, as well as pdc and adhB, on ethanol production. Overexpression of four glycolytic genes (pgi, pfkA, gapA, and pyk) in C. glutamicum significantly increased the rate of ethanol production. Overexpression of tpi, encoding triosephosphate isomerase, further enhanced productivity. Elevated expression of pdc and adhB increased ethanol yield, but not the rate of production. Fed-batch fermentation using an optimized strain resulted in ethanol production of 119 g/L from 245 g/L glucose with a yield of 95% of the theoretical maximum. Further metabolic engineering, including integration of the genes for xylose and arabinose metabolism, enabled consumption of glucose, xylose, and arabinose, and ethanol production (83 g/L) at a yield of 90 %. This study demonstrated that C. glutamicum has significant potential for the production of cellulosic ethanol.

  8. Analysis and Engineering of Metabolic Pathway Fluxes in Corynebacterium glutamicum

    Science.gov (United States)

    Wittmann, Christoph

    The Gram-positive soil bacterium Corynebacterium glutamicum was discovered as a natural overproducer of glutamate about 50 years ago. Linked to the steadily increasing economical importance of this microorganism for production of glutamate and other amino acids, the quest for efficient production strains has been an intense area of research during the past few decades. Efficient production strains were created by applying classical mutagenesis and selection and especially metabolic engineering strategies with the advent of recombinant DNA technology. Hereby experimental and computational approaches have provided fascinating insights into the metabolism of this microorganism and directed strain engineering. Today, C. glutamicum is applied to the industrial production of more than 2 million tons of amino acids per year. The huge achievements in recent years, including the sequencing of the complete genome and efficient post genomic approaches, now provide the basis for a new, fascinating era of research - analysis of metabolic and regulatory properties of C. glutamicum on a global scale towards novel and superior bioprocesses.

  9. Biofilm production by multiresistant Corynebacterium striatum associated with nosocomial outbreak

    Science.gov (United States)

    de Souza, Cassius; Faria, Yuri Vieira; Sant’Anna, Lincoln de Oliveira; Viana, Vanilda Gonçalves; Seabra, Sérgio Henrique; de Souza, Mônica Cristina; Vieira, Verônica Viana; Hirata, Raphael; Moreira, Lílian de Oliveira; de Mattos-Guaraldi, Ana Luíza

    2015-01-01

    Corynebacterium striatum is a potentially pathogenic microorganism that causes nosocomial outbreaks. However, little is known about its virulence factors that may contribute to healthcare-associated infections (HAIs). We investigated the biofilm production on abiotic surfaces of multidrug-resistant (MDR) and multidrug-susceptible (MDS) strains of C. striatum of pulsed-field gel electrophoresis types I-MDR, II-MDR, III-MDS and IV-MDS isolated during a nosocomial outbreak in Rio de Janeiro, Brazil. The results showed that C. striatum was able to adhere to hydrophilic and hydrophobic abiotic surfaces. The C. striatum 1987/I-MDR strain, predominantly isolated from patients undergoing endotracheal intubation procedures, showed the greatest ability to adhere to all surfaces. C. striatum bound fibrinogen to its surface, which contributed to biofilm formation. Scanning electron microscopy showed the production of mature biofilms on polyurethane catheters by all pulsotypes. In conclusion, biofilm production may contribute to the establishment of HAIs caused by C. striatum. PMID:25946249

  10. Structural basis for cytokinin production by LOG from Corynebacterium glutamicum.

    Science.gov (United States)

    Seo, Hogyun; Kim, Sangwoo; Sagong, Hye-Young; Son, Hyeoncheol Francis; Jin, Kyeong Sik; Kim, Il-Kwon; Kim, Kyung-Jin

    2016-08-10

    "Lonely guy" (LOG) has been identified as a cytokinin-producing enzyme in plants and plant-interacting fungi. The gene product of Cg2612 from the soil-dwelling bacterium Corynebacterium glutamicum was annotated as an LDC. However, the facts that C. glutamicum lacks an LDC and Cg2612 has high amino acid similarity with LOG proteins suggest that Cg2612 is possibly an LOG protein. To investigate the function of Cg2612, we determined its crystal structure at a resolution of 2.3 Å. Cg2612 functions as a dimer and shows an overall structure similar to other known LOGs, such as LOGs from Arabidopsis thaliana (AtLOG), Claviceps purpurea (CpLOG), and Mycobacterium marinum (MmLOG). Cg2612 also contains a "PGGXGTXXE" motif that contributes to the formation of an active site similar to other LOGs. Moreover, biochemical studies on Cg2612 revealed that the protein has phosphoribohydrolase activity but not LDC activity. Based on these structural and biochemical studies, we propose that Cg2612 is not an LDC family enzyme, but instead belongs to the LOG family. In addition, the prenyl-binding site of Cg2612 (CgLOG) comprised residues identical to those seen in AtLOG and CpLOG, albeit dissimilar to those in MmLOG. The work provides structural and functional implications for LOG-like proteins from other microorganisms.

  11. Histidine biosynthesis, its regulation and biotechnological application in Corynebacterium glutamicum.

    Science.gov (United States)

    Kulis-Horn, Robert K; Persicke, Marcus; Kalinowski, Jörn

    2014-01-01

    l-Histidine biosynthesis is an ancient metabolic pathway present in bacteria, archaea, lower eukaryotes, and plants. For decades l-histidine biosynthesis has been studied mainly in Escherichia coli and Salmonella typhimurium, revealing fundamental regulatory processes in bacteria. Furthermore, in the last 15 years this pathway has been also investigated intensively in the industrial amino acid-producing bacterium Corynebacterium glutamicum, revealing similarities to E. coli and S. typhimurium, as well as differences. This review summarizes the current knowledge of l-histidine biosynthesis in C. glutamicum. The genes involved and corresponding enzymes are described, in particular focusing on the imidazoleglycerol-phosphate synthase (HisFH) and the histidinol-phosphate phosphatase (HisN). The transcriptional organization of his genes in C. glutamicum is also reported, including the four histidine operons and their promoters. Knowledge of transcriptional regulation during stringent response and by histidine itself is summarized and a translational regulation mechanism is discussed, as well as clues about a histidine transport system. Finally, we discuss the potential of using this knowledge to create or improve C. glutamicum strains for the industrial l-histidine production.

  12. A combined approach for comparative exoproteome analysis of Corynebacterium pseudotuberculosis

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    Scrivens James H

    2011-01-01

    Full Text Available Abstract Background Bacterial exported proteins represent key components of the host-pathogen interplay. Hence, we sought to implement a combined approach for characterizing the entire exoproteome of the pathogenic bacterium Corynebacterium pseudotuberculosis, the etiological agent of caseous lymphadenitis (CLA in sheep and goats. Results An optimized protocol of three-phase partitioning (TPP was used to obtain the C. pseudotuberculosis exoproteins, and a newly introduced method of data-independent MS acquisition (LC-MSE was employed for protein identification and label-free quantification. Additionally, the recently developed tool SurfG+ was used for in silico prediction of sub-cellular localization of the identified proteins. In total, 93 different extracellular proteins of C. pseudotuberculosis were identified with high confidence by this strategy; 44 proteins were commonly identified in two different strains, isolated from distinct hosts, then composing a core C. pseudotuberculosis exoproteome. Analysis with the SurfG+ tool showed that more than 75% (70/93 of the identified proteins could be predicted as containing signals for active exportation. Moreover, evidence could be found for probable non-classical export of most of the remaining proteins. Conclusions Comparative analyses of the exoproteomes of two C. pseudotuberculosis strains, in addition to comparison with other experimentally determined corynebacterial exoproteomes, were helpful to gain novel insights into the contribution of the exported proteins in the virulence of this bacterium. The results presented here compose the most comprehensive coverage of the exoproteome of a corynebacterial species so far.

  13. Updates on industrial production of amino acids using Corynebacterium glutamicum.

    Science.gov (United States)

    Wendisch, Volker F; Jorge, João M P; Pérez-García, Fernando; Sgobba, Elvira

    2016-06-01

    L-Amino acids find various applications in biotechnology. L-Glutamic acid and its salts are used as flavor enhancers. Other L-amino acids are used as food or feed additives, in parenteral nutrition or as building blocks for the chemical and pharmaceutical industries. L-amino acids are synthesized from precursors of central carbon metabolism. Based on the knowledge of the biochemical pathways microbial fermentation processes of food, feed and pharma amino acids have been developed. Production strains of Corynebacterium glutamicum, which has been used safely for more than 50 years in food biotechnology, and Escherichia coli are constantly improved using metabolic engineering approaches. Research towards new processes is ongoing. Fermentative production of L-amino acids in the million-ton-scale has shaped modern biotechnology and its markets continue to grow steadily. This review focusses on recent achievements in strain development for amino acid production including the use of CRISPRi/dCas9, genome-reduced strains, biosensors and synthetic pathways to enable utilization of alternative carbon sources.

  14. Functional characterization of Corynebacterium glutamicum mycothiol S-conjugate amidase.

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    Meiru Si

    Full Text Available The present study focuses on the genetic and biochemical characterization of mycothiol S-conjugate amidase (Mca of Corynebacterium glutamicum. Recombinant C. glutamicum Mca was heterologously expressed in Escherichia coli and purified to apparent homogeneity. The molecular weight of native Mca protein determined by gel filtration chromatography was 35 kDa, indicating that Mca exists as monomers in the purification condition. Mca showed amidase activity with mycothiol S-conjugate of monobromobimane (MSmB in vivo while mca mutant lost the ability to cleave MSmB. In addition, Mca showed limited deacetylase activity with N-acetyl-D-glucosamine (GlcNAc as substrate. Optimum pH for amidase activity was between 7.5 and 8.5, while the highest activity in the presence of Zn2+ confirmed Mca as a zinc metalloprotein. Amino acid residues conserved among Mca family members were located in C. glutamicum Mca and site-directed mutagenesis of these residues indicated that Asp14, Tyr137, His139 and Asp141 were important for activity. The mca deletion mutant showed decreased resistance to antibiotics, alkylating agents, oxidants and heavy metals, and these sensitive phenotypes were recovered in the complementary strain to a great extent. The physiological roles of Mca in resistance to various toxins were further supported by the induced expression of Mca in C. glutamicum under various stress conditions, directly under the control of the stress-responsive extracytoplasmic function-sigma (ECF-σ factor SigH.

  15. Effect of Corynebacterium glutamicum on Livestock Material Burial Treatment.

    Science.gov (United States)

    Kim, Bit-Na; Cho, Ho-Seong; Cha, Yougin; Park, Joon-Kyu; Kim, Geonha; Kim, Yang-Hoon; Min, Jiho

    2016-08-28

    In recent years, foot-and-mouth disease has occurred in all parts of the world. The animals with the disease are buried in the ground; therefore, their concentration could affect ground or groundwater. Moreover, the complete degradation of carcasses is not a certainty, and their disposal is important to prevent humans, livestock, and the environment from being affected with the disease. The treatment of Corynebacterium glutamicum is a feasible method to reduce the risk of carcass decomposition affecting humans or the environment. Therefore, this study aimed to investigate the effect of C. glutamicum on the soil environment with a carcass. The composition of amino acids in the soil treated with C. glutamicum was generally higher than those in the untreated soil. Moreover, the plant root in the soil samples treated with C. glutamicum had 84.0% amino acids relative to the standard value and was similar to that of the control. The results of this study suggest the possibility to reduce the toxicity of a grave land containing animals with this disease.

  16. Bio-based production of organic acids with Corynebacterium glutamicum.

    Science.gov (United States)

    Wieschalka, Stefan; Blombach, Bastian; Bott, Michael; Eikmanns, Bernhard J

    2013-03-01

    The shortage of oil resources, the steadily rising oil prices and the impact of its use on the environment evokes an increasing political, industrial and technical interest for development of safe and efficient processes for the production of chemicals from renewable biomass. Thus, microbial fermentation of renewable feedstocks found its way in white biotechnology, complementing more and more traditional crude oil-based chemical processes. Rational strain design of appropriate microorganisms has become possible due to steadily increasing knowledge on metabolism and pathway regulation of industrially relevant organisms and, aside from process engineering and optimization, has an outstanding impact on improving the performance of such hosts. Corynebacterium glutamicum is well known as workhorse for the industrial production of numerous amino acids. However, recent studies also explored the usefulness of this organism for the production of several organic acids and great efforts have been made for improvement of the performance. This review summarizes the current knowledge and recent achievements on metabolic engineering approaches to tailor C. glutamicum for the bio-based production of organic acids. We focus here on the fermentative production of pyruvate, L- and D-lactate, 2-ketoisovalerate, 2-ketoglutarate, and succinate. These organic acids represent a class of compounds with manifold application ranges, e.g. in pharmaceutical and cosmetics industry, as food additives, and economically very interesting, as precursors for a variety of bulk chemicals and commercially important polymers.

  17. Corynebacterium pseudotuberculosis associated with otitis media-interna in goats

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    Rhoda Leask

    2013-02-01

    Full Text Available Corynebacterium pseudotuberculosis or caseous lymphadenitis is a common condition in sheep and goats. Two cases are described involving otitis media-interna and, in one case, cerebellar abscessation. The first case began with otitis externa and progressed to cerebellar abscessation, presumably as a result of C. pseudotuberculosis infection based on the macroscopic appearance of the abscess. The second case of otitis media-interna involved C. pseudotuberculosis with parasitic encephalitis or secondary meningo-encephalitis. Caseous lymphadenitis is a worldwide problem in livestock and also has zoonotic implications. Antimicrobial therapy of abscesses is often unrewarding due to the thick encapsulation of the abscesses and the extremely contagious nature of the organism. Alternative measures of treating this condition must be sought. In flocks or herds where caseous lymphadenitis has been diagnosed, it should be considered as a differential diagnosis for neurological conditions. The potential for spread must be kept in mind when it is suspected to be the cause of otitis in livestock.

  18. Diagnostic and experimental study of Corynebacterium renale isolated from urinary tract infection of cattle

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    S. A. Hussein

    2011-01-01

    Full Text Available The study includes isolation and identification of Corynebacterium renale from urine of cow apparently suffering from urinary tract infection. C. renale represent highest isolate 49. 99% followed by Corynebacterium pyogenes 24.24% from the total number of Corynebacterium 74.23%. on the other hand Staphylococcus saprophyticus also isolated from urine samples 25.75%. Since C. renale was isolated at highest rate we studied its pathogenesis via inoculation of isolate intraperitoneally into white Swiss mice. Results showed that C. renale type I has ability to produce kidney damage after 48 hr. post inoculation revealed embolic glomeruler nephritis with less number of C. renale, also there is infiltration of polymorphnuclear inflammatory cell and nephrosis, in addition to vacular degeneration, coagulative necrosis with blood vessel congestion in liver tissue.

  19. Diphtheria Antibodies and T lymphocyte Counts in Patients Infected with HIV-1

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    Francisco A. B. Speranza

    2012-09-01

    Full Text Available We assessed the IgG levels anti-diphtheria (D-Ab and T cell counts (CD4+ and CD8+ in HIV-1 infected subjects undergoing or not highly active antiretroviral therapy (HAART. Approximately 70% of all HIV-1 patients were unprotected against diphtheria. There were no differences in D-Ab according to CD4 counts. Untreated patients had higher D-Ab (geometric mean of 0.62 IU/ml than HAART-patients (geometric mean of 0.39 IU/ml. The data indicated the necessity of keeping all HIV-1 patients up-to-date with their vaccination.

  20. Seroepidemiology of diphtheria and tetanus among children and young adults in Tajikistan: nationwide population-based survey, 2010.

    Science.gov (United States)

    Khetsuriani, Nino; Zakikhany, Katherina; Jabirov, Shamsiddin; Saparova, Nargis; Ursu, Pavel; Wannemuehler, Kathleen; Wassilak, Steve; Efstratiou, Androulla; Martin, Rebecca

    2013-10-01

    Tajikistan had a major diphtheria outbreak (≈ 10,000 cases) in the 1990 s, which was controlled after nationwide immunization campaigns with diphtheria-tetanus toxoid in 1995 and 1996. Since 2000, only 52 diphtheria cases have been reported. However, in coverage surveys conducted in 2000 and 2005, diphtheria-tetanus-pertussis vaccine coverage was lower than administratively reported estimates raising concerns about potential immunity gaps. To further assess population immunity to diphtheria in Tajikistan, diphtheria antibody testing was included in a large-scale nationwide serosurvey for vaccine-preventable diseases conducted in connection with a poliomyelitis outbreak in 2010. In addition, the serosurvey provided an opportunity to assess population immunity to tetanus. Residents of all regions of Tajikistan aged 1-24 years were included in the serosurvey implemented during September-October 2010. Participants were selected through stratified cluster sampling. Specimens were tested for diphtheria antibodies using a Vero cell neutralization assay and for tetanus antibodies using an anti-tetanus IgG ELISA. Antibody concentrations ≥ 0.1 IU/mL were considered seropositive. Overall, 51.4% (95% CI, 47.1%-55.6%) of participants were seropositive for diphtheria and 78.9% (95% CI, 74.7%-82.5%) were seropositive for tetanus. The lowest percentages of seropositivity for both diseases were observed among persons aged 10-19 years: diphtheria seropositivity was 37.1% (95% CI, 31.0%-43.7%) among 10-14 year-olds, and 35.3% (95% CI, 29.9%-41.1%) among 15-19 year-olds; tetanus seropositivity in respective age groups was 65.3% (95% CI, 58.4%-71.6%) and 70.1% (95% CI, 64.5%-75.2%). Population immunity for diphtheria in Tajikistan is low, particularly among 10-19 year-olds. Population immunity to tetanus is generally higher than for diphtheria, but is suboptimal among 10-19 year-olds. These findings highlight the need to improve routine immunization service delivery, and support a

  1. Sensitivity of cancer cells to truncated diphtheria toxin.

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    Yi Zhang

    Full Text Available BACKGROUND: Diphtheria toxin (DT has been utilized as a prospective anti-cancer agent for the targeted delivery of cytotoxic therapy to otherwise untreatable neoplasia. DT is an extremely potent toxin for which the entry of a single molecule into a cell can be lethal. DT has been targeted to cancer cells by deleting the cell receptor-binding domain and combining the remaining catalytic portion with targeting proteins that selectively bind to the surface of cancer cells. It has been assumed that "receptorless" DT cannot bind to and kill cells. In the present study, we report that "receptorless" recombinant DT385 is in fact cytotoxic to a variety of cancer cell lines. METHODS: In vitro cytotoxicity of DT385 was measured by cell proliferation, cell staining and apoptosis assays. For in vivo studies, the chick chorioallantoic membrane (CAM system was used to evaluate the effect of DT385 on angiogenesis. The CAM and mouse model system was used to evaluate the effect of DT385 on HEp3 and Lewis lung carcinoma (LLC tumor growth, respectively. RESULTS: Of 18 human cancer cell lines tested, 15 were affected by DT385 with IC(50 ranging from 0.12-2.8 microM. Furthermore, high concentrations of DT385 failed to affect growth arrested cells. The cellular toxicity of DT385 was due to the inhibition of protein synthesis and induction of apoptosis. In vivo, DT385 diminished angiogenesis and decreased tumor growth in the CAM system, and inhibited the subcutaneous growth of LLC tumors in mice. CONCLUSION: DT385 possesses anti-angiogenic and anti-tumor activity and may have potential as a therapeutic agent.

  2. Nondiphtherial Corynebacterium species isolated from clinical specimens of patients in a university hospital, Rio de Janeiro, Brazil

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    Camello Thereza Cristina Ferreira

    2003-01-01

    Full Text Available Over a five-year period, 163 strains of Corynebacterium sp. were recovered from different clinical specimens of patients from a Brazilian University hospital. Genitourinary tract and intravenous sites specimens were the most frequent sources of corynebacteria (46.62%. Corynebacterium amycolatum (29.55%, Corynebacterium minutissimum (20.45% and Corynebacterium pseudodiphtheriticum (13.63% were the predominant species found in genitourinary tract. C. minutissimum (24.14% and Corynebacterium propinquum (17.24% in surgical and/or other skin wounds and abscesses; Corynebacterium xerosis (25%, C. amycolatum (21.87% and C. pseudodiphtheriticum (18.75% in intravenous sites; C. pseudodiphtheriticum (33.33% and C. propinquum (33.33% in lower respiratory tract. Microorganisms were all susceptible to vancomycin and most of the species was predominantly resistant to beta-lactams. Antimicrobial susceptibility patterns of corynebacteria were not predictable. Multiple antibiotic resistance observed in C. jeikeium was also found among C. xerosis, C. minutissimum, C. afermentans, C. propinquum, C. amycolatum and C. pseudodiphtheriticum strains. Data suggest awareness of clinicians and microbiologists to nosocomial infections especially due to antimicrobial multiresistant strains of Corynebacterium sp.

  3. Investigation of immunity level against diphtheria and reinforcement of immunity by booster vaccination for infection control staff in Okayama prefecture.

    Science.gov (United States)

    Nakajima, Hiroshi; Kariya, Hideaki; Ohata, Ritsuko; Ogura, Hajime

    2008-03-01

    The prevalence of immunity against diphtheria among Okayama local government staff members involved in diphtheria infection control was measured. Diphtheria booster vaccination was administered to staff members with low antitoxin levels ( or =0.1 IU/ml), and the remaining 157 (63.3%) showed levels of diphtheria-pertussis mixed vaccine (born in 1958-1967) and diphtheria-pertussis-tetanus mixed vaccine (born in 1968-) (58.3-61.0%) groups than in diphtheria vaccine (born in 1948-1957) and non-vaccinated (born until 1947) (7.4-18.9%) groups. Though antitoxin levels of 13 (68.4%) out of 19 staff members given booster vaccinations increased to 0.1 IU/ml, 50% of these individuals then showed levels of or =0.1 IU/ml in the non-booster vaccination group maintained their immunity levels for 2-4 years, independent of their history of vaccination. To ensure that staff members of the local government have fully protective antitoxin levels against diphtheria, periodical confirmation of antitoxin levels and booster vaccination should both be systematically carried out.

  4. Metabolic engineering of Corynebacterium glutamicum for methanol metabolism.

    Science.gov (United States)

    Witthoff, Sabrina; Schmitz, Katja; Niedenführ, Sebastian; Nöh, Katharina; Noack, Stephan; Bott, Michael; Marienhagen, Jan

    2015-03-01

    Methanol is already an important carbon feedstock in the chemical industry, but it has found only limited application in biotechnological production processes. This can be mostly attributed to the inability of most microbial platform organisms to utilize methanol as a carbon and energy source. With the aim to turn methanol into a suitable feedstock for microbial production processes, we engineered the industrially important but nonmethylotrophic bacterium Corynebacterium glutamicum toward the utilization of methanol as an auxiliary carbon source in a sugar-based medium. Initial oxidation of methanol to formaldehyde was achieved by heterologous expression of a methanol dehydrogenase from Bacillus methanolicus, whereas assimilation of formaldehyde was realized by implementing the two key enzymes of the ribulose monophosphate pathway of Bacillus subtilis: 3-hexulose-6-phosphate synthase and 6-phospho-3-hexuloisomerase. The recombinant C. glutamicum strain showed an average methanol consumption rate of 1.7 ± 0.3 mM/h (mean ± standard deviation) in a glucose-methanol medium, and the culture grew to a higher cell density than in medium without methanol. In addition, [(13)C]methanol-labeling experiments revealed labeling fractions of 3 to 10% in the m + 1 mass isotopomers of various intracellular metabolites. In the background of a C. glutamicum Δald ΔadhE mutant being strongly impaired in its ability to oxidize formaldehyde to CO2, the m + 1 labeling of these intermediates was increased (8 to 25%), pointing toward higher formaldehyde assimilation capabilities of this strain. The engineered C. glutamicum strains represent a promising starting point for the development of sugar-based biotechnological production processes using methanol as an auxiliary substrate.

  5. Activity of disinfectants and biofilm production of Corynebacterium pseudotuberculosis

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    Maria da C.A. Sá

    2013-11-01

    Full Text Available To verify the occurrence of caseous lymphadenitis in sheep and goats on farms of Pernambuco, Brazil, and in animals slaughtered in two Brazilian cities (Petrolina/PE and Juazeiro/BA, and to characterize the susceptibility profile of Corynebacterium pseudotuberculosis to disinfectants and antimicrobials, and its relationship with biofilm production were the objectives of this study. 398 samples were tested for sensitivity to antimicrobial drugs, disinfectants, and biofilm production. Among the 108 samples collected on the properties, 75% were positive for C. pseudotuberculosis. Slaughterhouse samples indicated an occurrence of caseous lymphadenitis in 15.66% and 6.31% for animals slaughtered in Petrolina and Juazeiro respectively. With respect to antimicrobials, the sensitivity obtained was 100% for florfenicol and tetracycline; 99.25% for enrofloxacin, ciprofloxacin and lincomycin; 98.99% for cephalothin; 98.74% for norfloxacin and sulfazotrim; 97.74% for gentamicin; 94.22% for ampicillin; 91.71% for amoxicillin; 91.21% for penicillin G; 89.19% for neomycin and 0% for novobiocin. In analyzes with disinfectants, the efficiency for chlorhexidine was 100%, 97.20% for quaternary ammonium, 87.40% for chlorine and 84.40% for iodine. 75% of the isolates were weak or non-biofilm producers. For the consolidated biofilm, found that iodine decreased biofilm formation in 13 isolates and quaternary ammonia in 11 isolates. The reduction of the biofilm formation was observed for iodine and quaternary ammonium in consolidated biofilm formation in 33% and 28% of the isolates, respectively. The results of this study highlight the importance of establishing measures to prevent and control the disease.

  6. Seroepidemiology of diphtheria, tetanus, poliomyelitis and pertussis : evaluation of the national immunisation programme in the Netherlands

    NARCIS (Netherlands)

    Melker, de H.

    1999-01-01

    In view of the evaluation of the National Immunisation Programme in the Netherlands the main objectives were to obtain insight into the immunity to diphtheria, tetanus and poliomyelitis, into the occurrence of pertussis and to improve serodiagnosis of pertussis.In a population-based nationwide sampl

  7. Assessment of a mandatory tetanus, diphtheria, and pertussis vaccination requirement on vaccine uptake over time.

    Science.gov (United States)

    Weber, David J; Consoli, Stephanie A; Sickbert-Bennett, Emily; Rutala, William A

    2012-01-01

    Tetanus, diphtheria, and pertussis (Tdap) vaccine is recommended for all healthcare personnel who provide direct patient care unless medically contraindicated. Our university hospital made employment conditional upon receipt of Tdap vaccine. Implementation for newly hired employees quickly resulted in complete compliance, but achieving adherence among current workers required setting a termination date for noncompliance.

  8. Is diphtheria-tetanus-pertussis (DTP) associated with increased female mortality?

    DEFF Research Database (Denmark)

    Aaby, Peter; Ravn, Henrik; Fisker, Ane B;

    2016-01-01

    BACKGROUND: Ten years ago, we formulated two hypotheses about whole-cell diphtheria-tetanus-pertussis (DTP) vaccination: first, when given after BCG, DTP increases mortality in girls and, second, following DTP there is an increase in the female/male mortality rate ratio (MRR). A recent review by ...

  9. Seroprevalence of antibody against diphtheria among the population in Khon Kaen province, Thailand.

    Science.gov (United States)

    Bansiddhi, Hataichanok; Vuthitanachot, Viboonsuk; Vuthitanachot, Chanpim; Prachayangprecha, Slinporn; Theamboonlers, Apiradee; Poovorawan, Yong

    2015-03-01

    To assess diphtheria immunity in the northeastern region of Thailand, a seroepidemiological survey was undertaken in 2011 from 516 healthy individuals (age range 2-87 years) in Khon Kaen province. Diphtheria antitoxin levels were measured by enzyme-linked immunosorbent assay and titers of ≥0.1 IU/mL were considered to be protective antitoxin levels. Among the studied population, 94.8% have fully protective levels. The younger population (age range 2-19 years) has higher diphtheria immunity with seroprotection rates of 96.8% to 97.9%, compared with the adult population. The proportion of protective diphtheria antitoxin levels declines to 88.3% to 91.9% in the middle-aged group (20-50 years), and appeared to be higher again in the older age-group (50-70 years). To avoid epidemic spreading, promoting immunization booster programs will be helpful, especially among the adult population (20-50 years). Finally, this study may serve as a valuable guide in deciding exactly which age-groups should be targeted by such an effort. © 2012 APJPH.

  10. Effective humoral immunity against diphtheria and tetanus in patients with systemic lupus erythematosus or myasthenia gravis.

    Science.gov (United States)

    Csuka, Dorottya; Czirják, László; Hóbor, Renáta; Illes, Zsolt; Bánáti, Miklós; Rajczy, Katalin; Tordai, Attila; Füst, George

    2013-07-01

    Controversy exists about the effectiveness of vaccine-induced immune response in patients with immunoregulatory disorders. Our aim was to determine the antibody titers to diphtheria and tetanus in patients with either of two autoimmune diseases. 279 patients with SLE (205 females, aged 45.0 ± 13.8 years), 158 patients with myasthenia gravis (MG) (101 females, aged 55 ± 18.7 years) and 208 healthy subjects (122 females, aged 48 ± 14.6 years) were enrolled. Serum concentrations of diphtheria-antitoxin-IgG (A-DIPHTH) and tetanus-antitoxoid-IgG (A-TET) were determined with ELISA. Equal proportions of healthy subjects, as well as patients with SLE or MG exhibited proper antibody responses and immune protection against diphtheria and tetanus. In all three test groups, serum concentration of A-DIPHTH decreased significantly (p60-years-old) subjects. There were no significant differences among the groups in the age-related changes of A-TET and A-DIPHTH except that in diphtheria and tetanus infections in patients with SLE or MG is comparable to the healthy population. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Seroepidemiology of diphtheria, tetanus, poliomyelitis and pertussis : evaluation of the national immunisation programme in the Netherlands

    NARCIS (Netherlands)

    Melker, de H.

    1999-01-01

    In view of the evaluation of the National Immunisation Programme in the Netherlands the main objectives were to obtain insight into the immunity to diphtheria, tetanus and poliomyelitis, into the occurrence of pertussis and to improve serodiagnosis of pertussis.

    In a popul

  12. Standardization and validation of Vero cell assay for potency estimation of diphtheria antitoxin serum.

    Science.gov (United States)

    Kumar, Sunil; Kanwar, Sarika; Bansal, Vivek; Sehgal, Rakesh

    2009-10-01

    Diphtheria toxin has the capacity to block protein synthesis in cultured mammalian cells, and thus causing cell death. This capacity of diphtheria toxin was utilized for in-vitro neutralization test to determine antibody titer, using Vero cells, which have been found to be susceptible to diphtheria toxin. In the present study, a Vero cell assay was standardized and validated for potency estimation of diphtheria antitoxin serum (DATS). The results obtained by Vero cell assay were compared with in-vivo biological assay. High degree of correlation (+0.98) was found between in-vivo biological assay and in-vitro Vero cell assay. The assay has also been found to be effective in determining the rising antibody titer in the equines inducted in DATS production. The present study indicated that although biological assays hold the key for final potency estimations till date but in the future scenario in-vitro Vero cell assay may be a good alternative to in-vivo biological assay.

  13. 76 FR 27888 - Implantation or Injectable Dosage Form New Animal Drugs; Gonadotropin Releasing Factor-Diphtheria...

    Science.gov (United States)

    2011-05-13

    ... drug regulations to reflect approval of a new animal drug application (NADA) filed by Pfizer, Inc. The NADA provides for the veterinary prescription use of gonadotropin releasing factor-diphtheria toxoid...-5755, filed NADA 141-322 that provides for the veterinary prescription use of IMPROVEST...

  14. Septic arthritis of a native knee joint due to Corynebacterium striatum.

    Science.gov (United States)

    Westblade, Lars F; Shams, Farah; Duong, Scott; Tariq, Oosman; Bulbin, Alan; Klirsfeld, Dava; Zhen, Wei; Sakaria, Smita; Ford, Bradley A; Burnham, Carey-Ann D; Ginocchio, Christine C

    2014-05-01

    We report a case of septic arthritis of a native knee joint due to Corynebacterium striatum, a rare and unusual cause of septic arthritis of native joints. The isolate was identified by a combination of phenotypic, mass spectrometric, and nucleic acid-based assays and exhibited high-level resistance to most antimicrobials.

  15. Pancreatic panniculitis complicated by infection with Corynebacterium tuberculostearicum: A case report

    Directory of Open Access Journals (Sweden)

    S.H. Omland

    2014-01-01

    Full Text Available We present a case of pancreatic panniculitis in a patient with alcohol abuse where Corynebacterium tuberculostearicum was isolated from a pannicular nodule on the crus. The patient was started on linezolid treatment leading to regression of the patient's symptoms. Upon discontinuation of linezolid treatment progression of the skin symptoms progressed.

  16. Urosepsis caused by Globicatella sanguinis and Corynebacterium riegelii in an adult: case report and literature review.

    Science.gov (United States)

    Matsunami, Masatoshi; Matusnami, Masatoshi; Otsuka, Yoshihito; Ohkusu, Kiyofumi; Sogi, Misa; Kitazono, Hidetaka; Hosokawa, Naoto

    2012-08-01

    We report an extremely rare case of urosepsis caused by Globicatella sanguinis and Corynebacterium riegelii coinfection in a 94-year-old Japanese man with nephrolithiasis. Prompt identification of this coinfection is important so that effective antimicrobial coverage can be initiated.

  17. Infecções por Corynebacterium pseudotuberculosis em animais de produção

    OpenAIRE

    Motta, Rodrigo Garcia [UNESP; Cremasco, Arita de Cássia Marella [UNESP; Ribeiro,Marcio Garcia

    2010-01-01

    Corynebacterium pseudotuberculosis infections are characterized by chronic pyogranulotous process in several domestic animals. In equine, bovine and small ruminants the affection by this actinomycete lead to pectoral abscesses, ulcerative limphangites and caseous lymphadenitis, respectively. The present study reviewed the most-important aspects of C. psedotuberculosis infectons, in domestic ruminants and equines, with emphasis for virulence factors of microorganism, epidemiology, clinical man...

  18. Corynebacterium renale as a cause of reactions to the complement fixation test for Johne's disease

    NARCIS (Netherlands)

    Gilmour, N.J.L.; Goudswaard, J.

    Complement fixation (C.F.) tests and fluorescent antibody (F.A.) tests were carried out on sera from rabbits inoculated with Corynebacterium renale and Mycobacterium johnei, and on sera from cattle with C. renale pyelonephritis and with Johne's disease. Cross-reactions were a feature of the C.F.

  19. Corynebacterium kutscheri Infection of Skin and Soft Tissue following Rat Bite▿

    Science.gov (United States)

    Holmes, Natasha E.; Korman, Tony M.

    2007-01-01

    Corynebacterium kutscheri is a common bacterium isolated from the oral cavity of healthy mice and rats. We report the first well-documented case of C. kutscheri human infection which followed a rat bite. The microorganism was identified by conventional biochemical tests and confirmed by 16S rRNA gene sequence analysis. PMID:17670928

  20. Corynebacterium kutscheri infection of skin and soft tissue following rat bite.

    Science.gov (United States)

    Holmes, Natasha E; Korman, Tony M

    2007-10-01

    Corynebacterium kutscheri is a common bacterium isolated from the oral cavity of healthy mice and rats. We report the first well-documented case of C. kutscheri human infection which followed a rat bite. The microorganism was identified by conventional biochemical tests and confirmed by 16S rRNA gene sequence analysis.

  1. Recall responses to tetanus and diphtheria vaccination are frequently insufficient in elderly persons.

    Directory of Open Access Journals (Sweden)

    Birgit Weinberger

    Full Text Available Demographic changes and a more active life-style in older age have contributed to an increasing public awareness of the need for lifelong vaccination. Currently many older persons have been vaccinated against selected pathogens during childhood but lack regular booster immunizations. The impact of regular vaccinations when started late in life was analyzed in an open, explorative trial by evaluating the immune response against tetanus and diphtheria in healthy older individuals. 252 persons aged above 60 years received a booster vaccination against tetanus, diphtheria, pertussis and polio and a subcohort (n=87 was recruited to receive a second booster vaccination against tetanus, diphtheria and pertussis 5 years later. The percentage of unprotected individuals at the time of enrollment differed substantially for tetanus (12% and diphtheria (65%. Despite protective antibody concentrations 4 weeks after the first vaccination in almost all vaccinees, antibodies had again dropped below protective levels in 10% (tetanus and 45% (diphtheria of the cohort after 5 years. Protection was restored in almost all vaccinees after the second vaccination. No correlation between tetanus- and diphtheria-specific responses was observed, and antibody concentrations were not associated with age-related changes in the T cell repertoire, inflammatory parameters, or CMV-seropositivity suggesting that there was no general biological "non-responder type." Post-vaccination antibody concentrations depended on pre-existing plasma cells and B cell memory as indicated by a strong positive relationship between post-vaccination antibodies and pre-vaccination antibodies as well as antibody-secreting cells. In contrast, antigen-specific T cell responses were not or only weakly associated with antibody concentrations. In conclusion, our findings demonstrate that single shot vaccinations against tetanus and/or diphtheria do not lead to long-lasting immunity in many elderly persons

  2. Recall Responses to Tetanus and Diphtheria Vaccination Are Frequently Insufficient in Elderly Persons

    Science.gov (United States)

    Weinberger, Birgit; Schirmer, Michael; Matteucci Gothe, Raffaella; Siebert, Uwe; Fuchs, Dietmar; Grubeck-Loebenstein, Beatrix

    2013-01-01

    Demographic changes and a more active life-style in older age have contributed to an increasing public awareness of the need for lifelong vaccination. Currently many older persons have been vaccinated against selected pathogens during childhood but lack regular booster immunizations. The impact of regular vaccinations when started late in life was analyzed in an open, explorative trial by evaluating the immune response against tetanus and diphtheria in healthy older individuals. 252 persons aged above 60 years received a booster vaccination against tetanus, diphtheria, pertussis and polio and a subcohort (n=87) was recruited to receive a second booster vaccination against tetanus, diphtheria and pertussis 5 years later. The percentage of unprotected individuals at the time of enrollment differed substantially for tetanus (12%) and diphtheria (65%). Despite protective antibody concentrations 4 weeks after the first vaccination in almost all vaccinees, antibodies had again dropped below protective levels in 10% (tetanus) and 45% (diphtheria) of the cohort after 5 years. Protection was restored in almost all vaccinees after the second vaccination. No correlation between tetanus- and diphtheria-specific responses was observed, and antibody concentrations were not associated with age-related changes in the T cell repertoire, inflammatory parameters, or CMV-seropositivity suggesting that there was no general biological “non-responder type.” Post-vaccination antibody concentrations depended on pre-existing plasma cells and B cell memory as indicated by a strong positive relationship between post-vaccination antibodies and pre-vaccination antibodies as well as antibody-secreting cells. In contrast, antigen-specific T cell responses were not or only weakly associated with antibody concentrations. In conclusion, our findings demonstrate that single shot vaccinations against tetanus and/or diphtheria do not lead to long-lasting immunity in many elderly persons despite

  3. Seroepidemiology of diphtheria and pertussis in Beijing, China: A cross-sectional study.

    Science.gov (United States)

    Li, Xiaomei; Chen, Meng; Zhang, Tiegang; Li, Juan; Zeng, Yang; Lu, Li

    2015-01-01

    The aim of this study was to assess the level of humoral immunity against diphtheria and pertussis by measuring IgG to diphtheria toxoid (DT) and pertussis toxin (PT) in general population of Beijing. A total of 2147 subjects aged 0-74 y were selected with a random sample of resident population in Beijing. The information of socio-demographic characteristics, vaccination history, disease history of diphtheria and pertussis were collected for each subject by questionnaire. Serum samples were tested for IgG antibodies to DT and PT by using commercial ELISA kits. The overall positivity rate of anti-DT IgG was 66.28% with the mean concentration of 2.169 IU/ml. Age stratified data showed that the highest positivity rate of 97.63% was observed in 1-4 y and the rates decreased with age. The positivity rates were only around 50% or below since 25 y old. The positivity rate of anti-PT IgG was 12.34% with the mean concentration of 15.163 IU/ml. The highest level of positivity rate (22.23%) and antibody level (23.101 IU/ml) was seen in diphtheria was observed at 1 y and 6 y respectively, which was consistent with the current immunization schedule. But there was no significant increase of immunity to pertussis observed after booster immunization at 18-24 months, but the proportions of undetectable were lowest in diphtheria and all the age groups showed a low immunity to pertussis indicating the potential risk of transmission and outbreaks of the 2 diseases in Beijing.

  4. A Bordetella pertussis proteoliposome induces protection in mice without affecting the immunogenicity of diphtheria and tetanus toxoids in a trivalent formulation

    Science.gov (United States)

    2016-01-01

    In this study, a formulation of Bordetella pertussis proteoliposome (PLBp), diphtheria, and tetanus toxoids and alum (DT-PLBp) was evaluated as a trivalent vaccine candidate in BALB/c mice. Vaccine-induced protection was estimated using the intranasal challenge for pertussis and enzyme-linked immunosorbent assay fvto assess serological responses for diphtheria or tetanus. Both, diphtheria-tetanus-whole cell pertussis (DTP) and diphtheria-tetanus vaccines (DT) were used as controls. Animals immunized with DT-PLBp, PLBp alone, and DTP showed total reduction of CFU in lungs 7 days after intranasal challenge. Likewise, formulations DT-PLBp, DTP, and DT elicited antibody levels ≥2 IU/mL against tetanus and diphtheria, considered protective when neutralization tests are used. Overall, results showed that combination of PLBp with tetanus and diphtheria toxoids did not affect the immunogenicity of each antigen alone. PMID:27489808

  5. A Bordetella pertussis proteoliposome induces protection in mice without affecting the immunogenicity of diphtheria and tetanus toxoids in a trivalent formulation.

    Science.gov (United States)

    Castillo, Sonsire Fernández; Chovel, Mario Landys; Hernández, Niurka Gutiérrez; González, Lorena Corcho; Blanco, Amaya; Hernández, Daily Serrano; Medina, Mildrey Fariñas; Tito, Maydelis Álvarez; Quiñoy, José Luis Pérez

    2016-07-01

    In this study, a formulation of Bordetella pertussis proteoliposome (PLBp), diphtheria, and tetanus toxoids and alum (DT-PLBp) was evaluated as a trivalent vaccine candidate in BALB/c mice. Vaccine-induced protection was estimated using the intranasal challenge for pertussis and enzyme-linked immunosorbent assay fvto assess serological responses for diphtheria or tetanus. Both, diphtheria-tetanus-whole cell pertussis (DTP) and diphtheria-tetanus vaccines (DT) were used as controls. Animals immunized with DT-PLBp, PLBp alone, and DTP showed total reduction of CFU in lungs 7 days after intranasal challenge. Likewise, formulations DT-PLBp, DTP, and DT elicited antibody levels ≥2 IU/mL against tetanus and diphtheria, considered protective when neutralization tests are used. Overall, results showed that combination of PLBp with tetanus and diphtheria toxoids did not affect the immunogenicity of each antigen alone.

  6. Assessment of serologic immunity to diphtheria-tetanus-pertussis after treatment of Korean pediatric hematology and oncology patients.

    Science.gov (United States)

    Kwon, Hyo Jin; Lee, Jae-Wook; Chung, Nak-Gyun; Cho, Bin; Kim, Hack-Ki; Kang, Jin Han

    2012-01-01

    The aim of this study was to investigate the diphtheria-tetanus-pertussis antibody titers after antineoplastic treatment and to suggest an appropriate vaccination approach for pediatric hemato-oncologic patients. A total of 146 children with either malignancy in remission after cessation of therapy or bone marrow failure were recruited. All children had received routine immunization including diphtheria-tetanus-acellular pertussis vaccination before diagnosis of cancer. The serologic immunity to diphtheria, tetanus and pertussis was classified as: completely protective, partially protective, or non-protective. Non-protective serum antibody titer for diphtheria, tetanus and pertussis was detected in 6.2%, 11.6%, and 62.3% of patients, respectively, and partial protective serum antibody titer for diphtheria, tetanus and pertussis was seen in 37%, 28.1%, and 8.9% of patients. There was no significant correlation between the severity of immune defect and age, gender or underlying disease. Revaccination after antineoplastic therapy showed significantly higher levels of antibody for each vaccine antigen. Our data indicates that a large proportion of children lacked protective serum concentrations of antibodies against diphtheria, tetanus, and pertussis. This suggests that reimmunization of these patients is necessary after completion of antineoplastic treatment. Also, prospective studies should be undertaken with the aim of devising a common strategy of revaccination.

  7. Prevalence of diphtheria and tetanus antibodies among adults in Singapore: a national serological study to identify most susceptible population groups.

    Science.gov (United States)

    Ang, L W; James, L; Goh, K T

    2016-03-01

    In view of waning antitoxin titres over time after the last vaccine dose against diphtheria and tetanus, we determined the immunity levels in adults to identify most susceptible groups for protection in Singapore. Our study involved residual sera from 3293 adults aged 18-79 who had participated in a national health survey in 2010. IgG antibody levels were determined using commercial enzyme-linked immunosorbent assay. Overall, 92.0% (95% confidence interval [CI]: 91.1-92.9%) had at least basic protection against diphtheria (antibody levels ≥0.01 IU/ml), while 71.4% (95% CI: 69.8-72.9%) had at least short-term protection against tetanus (antibody levels >0.1 IU/ml). The seroprevalence declined significantly with age for both diseases; the drop was most marked in the 50- to 59-year age group for diphtheria and 60- to 69-year age group for tetanus. There was a significant difference in seroprevalence by residency for diphtheria (92.8% among Singapore citizens versus 87.1% among permanent residents; P = 0.001). The seroprevalence for tetanus was significantly higher among males (83.2%) than females (62.4%) (P diphtheria and tetanus, particularly those travelling to areas where diphtheria is endemic or epidemic. © The Author 2015. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. Lack of significant differences in immunity against diphtheria between populations of Eastern and Western regions of Poland.

    Science.gov (United States)

    Chudnicka, Alina; Walory, Jarosław

    2003-01-01

    Incidents of diphtheria in countries which were formerly part of the Soviet Union (Ukraine, Russia and Belorus) resulted in the need to evaluate thoroughly the effectiveness of preventive vaccination in Poland, especially in the border regions of the country where the biggest migration of population can be observed. The aim of this work was a comparison of the immunity to diphtheria in two geographically different regions of Poland--eastern (Lublin) and western (Zielona Gora) ones. It showed immunoprophylaxis to diphtheria that was implemented on these areas. Diphtheria antitoxin level (IgG) was determined with application of the ELISA method in 1236 (529/707) people. No significant differences were found in the level of antibodies in the groups 19 years of age in people below the protective titre (0.1 IU/ml). The difference occurring in the interval between 2nd and 18th year of life (in western Poland 7.6% and in eastern Poland 16%) may result from different implementation of the vaccination program in these regions (booster doses). Recommendations for vaccination to diphtheria in people over 25 years of age should be implemented especially in the frontier regions of Poland adjoining countries threatened with diphtheria occurrence.

  9. Seroprevalence of antibodies to pertussis and diphtheria among healthy adults in China.

    Science.gov (United States)

    Zhang, Qi; Han, Fulian; Nie, Qing; Ren, Hongyu; Zhang, Baoqiang; Liu, Qiyong; He, Qiushui; Shao, Zhujun

    2011-12-01

    Despite extensive childhood immunization, pertussis remains one of the world's leading causes of vaccine-preventable deaths. Incidence of pertussis in adolescents and adults has increased in many countries despite high vaccination coverage. In China, booster vaccinations against diphtheria, tetanus and pertussis are not used in adults, and little is known about pertussis incidence in the age group. The aim of this study was to determine seroprevalence of IgG antibodies to pertussis toxin (PT) and diphtheria among adults in China. Blood samples were obtained from 210 healthy adults aged 18-50 years in Weifang city, China during the period of May and June 2010. Serum IgG antibodies against PT (anti-PT IgG) and diphtheria were determined by the commercial ELISA kits, respectively. According to the kit, concentration of anti-PT IgG higher than 30 IU/mL was considered positive. An antibody concentration of ≥ 0.1 IU/mL was defined as evidence of seroprotection against diphtheria. The mean concentration of anti-PT IgG antibodies was 9.95 IU/mL (95% confidence interval (CI) 8.45-11.44). Eleven (5.24%) of the studied subjects were proved to be seropositive to pertussis. Of the 210 subjects, 161 (76.6%) had anti-diphtheria antibody concentration ≥ 0.1 IU/mL and 49 (23.3%) had the antibody concentration between 0.01 and 0.099 IU/mL. Our study indicated that about 5% of adults aged 18-50 years had positive anti-PT IgG antibodies, suggesting that adult pertussis is not uncommon in China. Although a high proportion of studied subjects had a protective level of immunity against diphtheria, the antibody level decreased with the increasing age of adults. Booster vaccinations against pertussis should be considered in adults in China. Copyright © 2011 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  10. Quantitative estimation of diphtheria and tetanus toxoids. 6. Use of different antibody titration methods for evaluation of immunogenicity in animals during potency assay of diphtheria toxoid.

    Science.gov (United States)

    Lyng, J; Heron, I

    1992-06-01

    Two diphtheria toxoid preparations were compared in potency assays in guinea-pigs using different methods for evaluation of the responses to vaccination. The methods used were the direct skin challenge (Schick test) and ELISA and VERO cell titration of antibodies. The different evaluation methods resulted in the same relative potencies between the toxoids. It was observed that when first-vaccination sera were compared with a second-vaccination serum, the relative antibody concentration depended on whether ELISA or VERO cell titration was used.

  11. The DtxR protein acting as dual transcriptional regulator directs a global regulatory network involved in iron metabolism of Corynebacterium glutamicum

    Directory of Open Access Journals (Sweden)

    Hüser Andrea T

    2006-02-01

    Full Text Available Abstract Background The knowledge about complete bacterial genome sequences opens the way to reconstruct the qualitative topology and global connectivity of transcriptional regulatory networks. Since iron is essential for a variety of cellular processes but also poses problems in biological systems due to its high toxicity, bacteria have evolved complex transcriptional regulatory networks to achieve an effective iron homeostasis. Here, we apply a combination of transcriptomics, bioinformatics, in vitro assays, and comparative genomics to decipher the regulatory network of the iron-dependent transcriptional regulator DtxR of Corynebacterium glutamicum. Results A deletion of the dtxR gene of C. glutamicum ATCC 13032 led to the mutant strain C. glutamicum IB2103 that was able to grow in minimal medium only under low-iron conditions. By performing genome-wide DNA microarray hybridizations, differentially expressed genes involved in iron metabolism of C. glutamicum were detected in the dtxR mutant. Bioinformatics analysis of the genome sequence identified a common 19-bp motif within the upstream region of 31 genes, whose differential expression in C. glutamicum IB2103 was verified by real-time reverse transcription PCR. Binding of a His-tagged DtxR protein to oligonucleotides containing the 19-bp motifs was demonstrated in vitro by DNA band shift assays. At least 64 genes encoding a variety of physiological functions in iron transport and utilization, in central carbohydrate metabolism and in transcriptional regulation are controlled directly by the DtxR protein. A comparison with the bioinformatically predicted networks of C. efficiens, C. diphtheriae and C. jeikeium identified evolutionary conserved elements of the DtxR network. Conclusion This work adds considerably to our currrent understanding of the transcriptional regulatory network of C. glutamicum genes that are controlled by DtxR. The DtxR protein has a major role in controlling the

  12. [New Swiss recommendations for adult boosters against pertussis, tetanus and diphtheria].

    Science.gov (United States)

    Siegrist, C-A

    2012-01-18

    Pertussis remains frequent in Switzerland (4000 yearly cases), where 80% of infants are infected by their family. To better protect parents and infants, a diphtheria-tetanus-pertussis (dTpa) booster is thus recommended at 25 years (catch-up 26-29 years), and to adults of any age in personal or professional contacts with infants diphtheria-tetanus boosters may be spaced every 20 years (dTpa at 25, dT at 45 and 65 years), avoiding useless immunizations. A 10-year interval remains recommended after the age of 65. The Swiss immunization plan thus adapts to recent evidence, to the risk of pushing the habits! Fortunately, a Swiss electronic immunization record allowing a vaccine check (www.myvaccines.ch) is now available for free to both the public and the professio-

  13. Impaired cellular immune response to diphtheria and tetanus vaccines in children after thoracic transplantation.

    Science.gov (United States)

    Urschel, Simon; Rieck, Birgit D; Birnbaum, Julia; Dalla Pozza, Robert; Rieber, Nikolaus; Januszewska, Katarzyna; Fuchs, Alexandra; West, Lori J; Netz, Heinrich; Belohradsky, Bernd H

    2011-05-01

    Safety and immunogenicity of diphtheria and tetanus booster vaccination were evaluated in 28 children after thoracic transplantation. Adverse events were documented in a patient diary. Blood was collected prior to and four wk after vaccination. Specific antibody concentrations were measured by ELISA. Lymphocytes were investigated for expression of activation markers (CD25, HLA-DR) by flow cytometry and proliferation assays with and without stimulation. Post-vaccination antibody titers were higher than prevaccination (p antibody levels against diphtheria (p antibodies was negatively correlated with tacrolimus dose, and impaired cellular immunity was associated with higher tacrolimus dose and steroid use. Adverse events were similar to the general population; serious adverse events and rejection did not occur. Vaccination with inactivated vaccines can be performed safely in immunosuppressed children after thoracic transplantation and induces protective antibody levels in the majority of patients. Impaired induction of specific cellular immunity is correlated with intensity of immunosuppression and may explain reduced sustainability of antibodies.

  14. Seroprevalence of antibodies to diphtheria, tetanus and pertussis among healthy adolescents and adults in Iran.

    Science.gov (United States)

    Pourakbari, Babak; Moradi, Behnaz; Mirzaee, Farin; Mahmoudi, Shima; Teymuri, Mostafa; Mamishi, Setareh

    2013-01-01

    Serologic data on diseases that are preventable by vaccine are useful to evaluate the success of immunization programs. In this study we evaluated the serologic levels of antibodies to diphtheria, tetanus, and pertussis. In a cross sectional study, a total of 360 people aged 10-25 years were randomly selected and classified by sex and age (10-14, 15-20, 21-25 years). Overall, 78.8% of people aged 10-25 years had fully protected levels of diphtheria antibody (> or = 0.1 IU/ML), and 89.7% had fully protected levels of tetanus antibody (> or = 0.1 IU/ML), 94.3% of women aged 15-25 years had anti tetanus antibody sufficient to protect against neonatal tetanus (> or = 0.1 IU/ML). Antibodies to Pertussis toxin (PT) were found in 44.2% samples but only 1.4% had fully protective levels. Antibodies to PT increased with age, ranging from 33.5% in aged 10-14 years to 54.6 % in aged 21-25 years. No differences were found between male and female, except for diphtheria in age group 21-25 years. Results of this study reveal that diphtheria and tetanus (dT) are efficient between booster doses. About pertussis, most people are susceptible to pertussis and increased PT antibodies with age suggest acquired asymptomatic Bordeella pertussis infection. Also B. pertussis infections in adolescents and adults are of concern, as they are the most important source of transmission of pertussis to young, unprotected infants. So one booster dose in adolescents and adults (as CDC recommended), to reduce mortality and morbidity in infants, is therefore suggested.

  15. Low seroprevalence of diphtheria, tetanus and pertussis in ambulatory adult patients: the need for lifelong vaccination.

    Science.gov (United States)

    Tanriover, Mine Durusu; Soyler, Canan; Ascioglu, Sibel; Cankurtaran, Mustafa; Unal, Serhat

    2014-07-01

    Tetanus, diphtheria, pertussis and measles are vaccine preventable diseases that have been reported to cause morbidity and mortality in adult population in the recent years. We aimed to document the seropositivity rates and vaccination indication for these four vaccine preventable diseases among adult and elderly patients who were seen as outpatients in a university hospital. Blood samples for tetanus, diphtheria, pertussis and measles antibodies were obtained. Results were evaluated with regards to protection levels and booster vaccine indications according to the cut-off values. A total of 1367 patients consented for the study and 1303 blood samples were available for analysis at the end of the study. The antibody levels against measles conferred protection in 98% of patients. However, 65% of the patients had no protection for diphtheria, 69% had no protection for tetanus and 90% of the patients had no protection for pertussis. Only 1.3% of the study population had seropositivity against three of the diseases-Tdap booster was indicated in 98.7%. Multivariable logistic regression showed that tetanus protection decreased with increasing age. Having a chronic disease was associated with a lower rate of protective antibodies for pertussis. We demonstrated very low rates of protection against three of the vaccine preventable diseases of childhood-diphtheria, pertussis and tetanus. Booster vaccinations are required in adult life in accordance with national and international adult vaccination guidelines. The concept of "lifelong vaccination" should be implemented and every encounter with the patient should be regarded as a chance for catch-up. Copyright © 2014 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  16. Malaria chemoprophylaxis and the serologic response to measles and diphtheria-tetanus-whole-cell pertussis vaccines

    Directory of Open Access Journals (Sweden)

    Saliou Pierre

    2005-11-01

    Full Text Available Abstract Background Acute malaria has been associated with a decreased antibody response to tetanus and diphtheria toxoids, meningococcal, salmonella, and Hib vaccines. Interest in giving malaria drug therapy and prevention at the time of childhood immunizations has increased greatly following recent trials of intermittent preventive therapy during infancy (IPTi, stimulating this re-analysis of unpublished data. The effect of malaria chemoprophylaxis on vaccine response was studied following administration of measles vaccines and diphtheria-tetanus-whole cell pertussis (DTP vaccines. Methods In 1975, six villages divided into two groups of children ≤74 months of age from Burkina Faso, were assigned to receive amodiaquine hydrochloride chemoprophylaxis (CH+ every two weeks for seven months or no chemoprophylaxis (CH-. After five months, children in each group received either one dose of measles or two doses of DTP vaccines. Results For recipients of the measles vaccine, the seroconversion rates in CH+ and CH- children, respectively, were 93% and 96% (P > 0.05. The seroresponse rates in CH+ and CH- children respectively, were 73% and 86% for diphtheria (P > 0.05 and 77% and 91% for tetanus toxoid (P > 0.05. In a subset analysis, in which only children who strictly adhered to chemoprophylaxis criteria were included, there were, likewise, no significant differences in seroconversion or seroresponse for measles, diphtheria, or tetanus vaccines (P > 0.05. While analysis for pertussis showed a 43% (CH+ and 67% (CH- response (P Conclusion Malaria chemoprophylaxis prior to vaccination in malaria endemic settings did not improve or impair immunogenicity of DTP and measles vaccines. This is the first human study to look at the association between malaria chemoprophylaxis and the serologic response to whole-cell pertussis vaccine.

  17. The Shiga and Shiga-Like Cytotoxins: Gene Regulation and Functional Analysis of the Binding Subunits

    Science.gov (United States)

    1989-05-05

    studies had demonstrated that the production of toxin by Corynebacterium diphtheriae and Clostridium tetani was inhibited by the presence of excess iron...For example, expression of the diphtheria toxin operon of the ~ phage of Corynebacterium diphtheriae has been postulated to be negatively regulated...constitutive-like mutant lysogen of Corynebacterium diphtheriae . J. Viral. 18:235-244. Newland, J. w., N. A. Strockbine, s. F. Miller, A. D. O’Brien, and

  18. Protective status of end-stage renal disease children against tetanus and diphtheria vaccination

    Directory of Open Access Journals (Sweden)

    Mohammadreza Modarresi

    2013-01-01

    Methods: This cross-sectional study was carried on 83 participants less than 18 years including 27 patients on hemodialysis or peritoneal dialysis and 56 normal populations from February 2008 until December 2008 at St. Alzahra hospital, Isfahan, Iran. To determine anti-tetanus and anti-diphtheria antibodies level, Tetanus IgG ELISA kit (IBL International, Germany, RE56901 and Diphtheria IgG ELISA kit (IBL International, Germany, RE56191 were used. The participants must not received immunoglobulin, blood products or immunosuppressive medication in the current 6 months. Results: The mean age of case and control group were 12.5 ± 2.7 years and 11.7 ± 3.3 years, respectively, P > 0.05. According to IgG levels, 93% of hemodialysis patients and approximately 87% of peritoneal dialysis children needed booster doses of diphtheria vaccination. The results for IgG titer against tetanus revealed that in 91% of hemodialysis patients and 83% of peritoneal dialysis children booster doses of tetanus were recommended. Conclusions: Booster doses of vaccines may be required in ESRD children. Measuring serum IgG levels against vaccines to define protective levels are recommended.

  19. Low tetanus, diphtheria and acellular pertussis (Tdap) vaccination coverage among HIV infected individuals in Austria.

    Science.gov (United States)

    Grabmeier-Pfistershammer, K; Herkner, H; Touzeau-Roemer, V; Rieger, A; Burgmann, H; Poeppl, W

    2015-07-31

    Current management guidelines of HIV infected adults include recommendation to immunization against common vaccine preventable diseases. This effort is hindered by the scarce knowledge regarding the immunization status of this especially vulnerable patient group. This study analyzed the serostatus for pertussis, diphtheria and tetanus of more than 700 HIV infected individuals residing in Austria. These individuals were representative for the Austrian HIV cohort regarding sex, age, transmission risk and HIV progression markers. Overall, 73.6% were on suppressive HAART, mean CD4 cell count was 603c/μl. Seropositivity was 84% for diphtheria, 51% for tetanus and 1% for pertussis. Migrants had a lower chance of tetanus seropositivity (OR 0.30 (CI 0.21 to 0.43)). Increase in CDC classification were associated with increased diphtheria seropositivity (OR 1.42 (CI 1.02 to 1.98)) and a CD4 nadirvaccination would be feasible in the majority of the seronegative patients. In patients with a CD4 count>200c/μl, 95% lacked seroprotection to at least one of the antigens included in the triple vaccine Tdap and could be vaccinated. Thus, a proactive approach would largely reduce the number of patients at risk for these vaccine-preventable diseases.

  20. Expression of ovine gamma interferon in Escherichia coli and Corynebacterium glutamicum.

    OpenAIRE

    Billman-Jacobe, H; Hodgson, A L; Lightowlers, M; Wood, P R; Radford, A J

    1994-01-01

    Bacteria of two species, Escherichia coli and Corynebacterium glutamicum, were used as hosts to express recombinant ovine gamma interferon as a fusion protein with glutathione S-transferase. The recombinant gamma interferon produced by both bacteria was biologically active in vitro and was recognized by anti-gamma interferon monoclonal antibodies. E. coli produced large amounts of soluble recombinant protein which could be purified by a simple affinity chromatography method. Only a small frac...

  1. Flocculation of fine fluorite particles with Corynebacterium xerosis and commercial long chain polymers

    Directory of Open Access Journals (Sweden)

    Rigo Lisandra N.

    2002-01-01

    Full Text Available This work aimed to study, comparatively, the flocculation of fluorite particles with Corynebacterium xerosis cells and three commercial long chain polymers. Best flocculation results were obtained with cells of C. xerosis and with an anionic polyacrylamide. Both were effective in solids removal and water clarification, although flocculation with C. xerosis cells requires a higher dosage of reagent per mass unit of processed ore.

  2. In Silico Genome-Scale Reconstruction and Validation of the Corynebacterium glutamicum Metabolic Network

    DEFF Research Database (Denmark)

    Kjeldsen, Kjeld Raunkjær; Nielsen, J.

    2009-01-01

    A genome-scale metabolic model of the Gram-positive bacteria Corynebacterium glutamicum ATCC 13032 was constructed comprising 446 reactions and 411 metabolite, based on the annotated genome and available biochemical information. The network was analyzed using constraint based methods. The model...... and lactate. Comparable flux values between in silico model and experimental values were seen, although some differences in the phenotypic behavior between the model and the experimental data were observed,...

  3. Draft Genome Sequence of Corynebacterium amycolatum Strain ICIS 53 Isolated from a Female Urogenital Tract.

    Science.gov (United States)

    Gladysheva, Irina V; Cherkasov, Sergey V; Khlopko, Yuriy A; Plotnikov, Andrey O; Gogoleva, Natalya E

    2016-11-10

    This report describes the draft genome sequence of Corynebacterium amycolatum strain ICIS 53, isolated from the reproductive tract of a healthy woman. The size of the genome was 2,460,257 bp (58.98% G+C content). Annotation revealed 2,173 coding sequences, including 2,076 proteins, 7 rRNA genes, and 53 tRNA genes.

  4. Meningoencefalite supurativa por Corynebacterium pseudotuberculosis em cabra com linfadenite caseosa: relato de caso

    OpenAIRE

    Santarosa,Bianca Paola; Dantas, Gabriela Nascimento [UNESP; Amorim, Reneé Laufer [UNESP; Chiacchio,Simone Biagio; Oliveira Filho, José Paes de [UNESP; Amorim,Rogério Martins; Ribeiro, Márcio Garcia [UNESP; Gonçalves,Roberto Calderon

    2014-01-01

    Suppurative lesions in the central nervous system of small ruminants may be caused by Corynebacterium pseudotuberculosis. This report describes a case of suppurative meningoencephalitis caused by C. pseudotuberculosis in goats treated in the Large Animal Clinic of FMVZ-UNESP/Botucatu, SP. The animal had anorexia, caseous lymphadenitis (CL), recumbency, opisthotonus, paddling movements and nystagmus. The CSF showed increased protein and lymphocytic pleocytosis. At necropsy there were localized...

  5. Cystic Neutrophilic Granulomatous Mastitis:  Association With Gram-Positive Bacilli and Corynebacterium.

    Science.gov (United States)

    Troxell, Megan L; Gordon, Nicole T; Doggett, J Stone; Ballard, Morgan; Vetto, John T; Pommier, Rodney F; Naik, Arpana M

    2016-05-01

    To determine whether cystic neutrophilic granulomatous mastitis (CNGM) can be associated with Gram-positive bacilli and Corynebacterium We reviewed our experience with 35 granulomatous mastitis patients over a 10-year period, including histologic pattern, Gram stain and other microbiologic data, clinical presentation, treatment and outcome. Biopsies from 19 patients demonstrated CNGM, while 16 patients had other patterns of granulomatous mastitis. Gram-positive organisms were seen within microcystic spaces in 16/19 CNGM, but 0/16 non-CNGM patients (P = .000). Culture or molecular studies demonstrated Corynebacterium species in three, all CNGM. Patients with CNGM were more likely to be younger, of Hispanic ethnicity, and born outside of the United States. Granulomatous mastitis resolved after a protracted course with widely variable treatment (antibiotics, surgery, steroids). Our data further support CNGM as an infectious disease; further study of Corynebacterium-directed therapy in CNGM is needed. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. High-level expression in Corynebacterium glutamicum of nitrile hydratase from Rhodococcus rhodochrous for acrylamide production.

    Science.gov (United States)

    Kang, Mi-Suk; Han, Sang-Soo; Kim, Mi-Young; Kim, Bu-Youn; Huh, Jong-Pil; Kim, Hak-Sung; Lee, Jin-Ho

    2014-05-01

    The nhhBAG gene of Rhodococcus rhodochrous M33 that encodes nitrile hydratase (NHase), converting acrylonitrile into acrylamide, was cloned and expressed in Corynebacterium glutamicum under the control of an ilvC promoter. The specific enzyme activity in recombinant C. glutamicum cells was about 13.6 μmol/min/mg dry cell weight (DCW). To overexpress the NHase, five types of plasmid variants were constructed by introducing mutations into 80 nucleotides near the translational initiation region (TIR) of nhhB. Of them, pNBM4 with seven mutations showed the highest NHase activity, exhibiting higher expression levels of NhhB and NhhA than wild-type pNBW33, mainly owing to decreased secondary-structure stability and an introduction of a conserved Shine-Dalgarno sequence in the translational initiation region. In a fed-batch culture of recombinant Corynebacterium cells harboring pNBM4, the cell density reached 53.4 g DCW/L within 18 h, and the specific and total enzyme activities were estimated to be 37.3 μmol/min/mg DCW and 1,992 μmol/min/mL, respectively. The use of recombinant Corynebacterium cells for the production of acrylamide from acrylonitrile resulted in a conversion yield of 93 % and a final acrylamide concentration of 42.5 % within 6 h when the total amount of fed acrylonitrile was 456 g.

  7. Interactions of Pseudomonas aeruginosa and Corynebacterium spp. with non-phagocytic brain microvascular endothelial cells and phagocytic Acanthamoeba castellanii.

    Science.gov (United States)

    Siddiqui, Ruqaiyyah; Lakhundi, Sahreena; Khan, Naveed Ahmed

    2015-06-01

    Several lines of evidence suggest that Acanthamoeba interact with bacteria, which may aid in pathogenic bacterial transmission to susceptible hosts, and these interactions may have influenced evolution of bacterial pathogenicity. In this study, we tested if Gram-negative Pseudomonas aeruginosa and Gram-positive Corynebacterium spp. can associate/invade and survive inside Acanthamoeba castellanii trophozoites and cysts, as well as non-phagocytic human brain microvascular endothelial cells. The results revealed that both Corynebacterium spp. and P. aeruginosa were able to associate as well as invade and/or taken up by the phagocytic A. castellanii trophozoite. In contrast, P. aeruginosa exhibited higher association as well as invasion of non-phagocytic HBMEC compared with Corynebacterium spp. Notably, P. aeruginosa remained viable during the encystment process and exhibited higher levels of recovery from mature cysts (74.54 bacteria per amoebae) compared with Corynebacterium spp. (2.69 bacteria per amoeba) (P < 0.05). As Acanthamoeba cysts can be airborne, these findings suggest that Acanthamoeba is a potential vector in the transmission of P. aeruginosa to susceptible hosts. When bacterial-ridden amoebae were exposed to favourable (nutrient-rich) conditions, A. castellanii emerged as vegetative trophozoites and remained viable, and likewise viable P. aeruginosa were also observed but rarely any Corynebacterium spp. were observed. Correspondingly, P. aeruginosa but not Corynebacterium spp. exhibited higher cytotoxicity to non-phagocytic HBMEC, producing more than 75% cell death in 24 h, compared to 20% cell death observed with Corynebacterium spp. Additionally, it was observed that the bacterial conditioned medium had no negative effect on A. castellanii growth. Further characterization of amoebal and bacterial interactions will assist in identifying the role of Acanthamoeba in the transmission and evolution of pathogenic bacteria.

  8. The conjugation of diphtheria toxin T domain to poly(ethylenimine) based vectors for enhanced endosomal escape during gene transfection.

    Science.gov (United States)

    Kakimoto, Shinji; Hamada, Tsutomu; Komatsu, Yuuki; Takagi, Masahiro; Tanabe, Toshizumi; Azuma, Hideki; Shinkai, Seiji; Nagasaki, Takeshi

    2009-01-01

    The endosomal escape is a well-known serious obstacle for non-viral gene delivery. This is because of an acidic and enzymatic degradation of the contents of the endosome/lysosome. Therefore, the internalized gene needs to be efficient released into the cytosol to obtain the efficiently transfection efficiency. On the other hand, the diphtheria toxin T domain fuses with endosome membrane by pH decrease, then enhances the endosomal escape of the diphtheria toxin C fragment. In this study, we constructed diphtheria toxin T domain-conjugated poly(ethylenimine)s (PEI) polyplex for enhancing the endosomal escape of exogenous gene. The conjugation of diphtheria toxin T domain with PEI/pDNA polyplex leads to the significant enhancement of transfection efficiency when compared with plain PEI/pDNA polyplex. The pH-responsive increase in hydrophobicity of the diphtheria toxin T domain might not only trigger the perturbation of the endocytic vesicle membrane but might also increase the membrane permeability.

  9. An antibody induction method in mice for the potency assays of diphtheria and tetanus components in combined vaccines.

    Science.gov (United States)

    Maheshwari, S C; Sharma, S B; Kumar, A; Sokhey, J

    1998-09-01

    Eleven batches of Adsorbed Diphtheria-Tetanus (DT) vaccines and thirteen batches of Adsorbed Diphtheria-Pertussis-Tetanus (DTP) vaccines were tested for the potency of diphtheria and tetanus components by an Antibody Induction Method (AIM) developed in mice. The potency results obtained were found comparable and did not show any statistically significant difference with those obtained by WHO recommended lethal challenge tests for diphtheria in guinea pigs and for tetanus in mice. AIM in mice is more economical as both diphtheria and tetanus components of combined vaccine can be tested in the same experiment and the procedure also eliminates the use of guinea pigs required in the lethal challenge/conventional tests. The data obtained while testing tetanus component by the conventional antibody induction (IP) method in guinea pigs suggests that minimum requirements laid down in i.p. is too low which may be fixed as at least 3 out of 9 guinea pig sera and should contain > or = 4 units of tetanus antitoxin per ml.

  10. A cross-sectional study of tetanus and diphtheria antibody concentrations post vaccination among lung transplant patients compared with healthy individuals.

    Science.gov (United States)

    Rohde, K A; Cunningham, K C; Henriquez, K M; Nielsen, A R; Worzella, S L; Hayney, M S

    2014-12-01

    Lung transplant (LuTx) patients are routinely immunized against tetanus and diphtheria. However, few studies have been done to measure serologic immunity in the transplant population. The primary objective of this study was to compare tetanus and diphtheria antibody concentrations in LuTx vs. healthy subjects. Serum was used from an available sample of 111 total individuals (n = 36 healthy; n = 75 LuTx). Tetanus and diphtheria antibody concentrations were measured using an enzyme-linked immunosorbant assay method. A statistically significant difference in both tetanus and diphtheria antibody concentrations was found between the groups. The median concentration of tetanus antibody was higher for healthy individuals compared with the LuTx group (3.2 IU/mL [1.2-5.2 interquartile range {IQR}] vs. 1.3 IU/mL [0.4-2.6 IQR], respectively; P = 0.0001). No difference in time was found since the last tetanus-diphtheria vaccine or tetanus-diphtheria-pertussis vaccine dose between the groups (healthy 76.5 months [16-114 IQR] vs. LuTx 74.5 months [45-118 IQR]; P = 0.44). Tetanus and diphtheria immunizations are recommended for LuTx patients to reduce the risk of infection. Because the LuTx group has lower antibody concentrations, further studies should investigate the possible need for more frequent tetanus and diphtheria boosters. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Immunogenicity and safety of one dose of diphtheria, tetanus, acellular pertussis and poliomyelitis vaccine (Repevax®) followed by two doses of diphtheria, tetanus and poliomyelitis vaccine (Revaxis®) in adults aged ≥ 40 years not receiving a diphtheria- and tetanus-containing vaccination in the last 20 years.

    Science.gov (United States)

    Dominicus, Rolf; Galtier, Florence; Richard, Patrick; Baudin, Martine

    2014-06-30

    The immunogenicity and safety of one dose of Tdap-IPV (tetanus, diphtheria, acellular pertussis and inactivated poliomyelitis vaccine) and two doses of Td-IPV (tetanus, diphtheria and inactivated poliomyelitis vaccine) were assessed in adults who had not received a diphtheria- and tetanus-containing vaccine in the last 20 years. This open-label, multicentre study was conducted in adults aged ≥ 40 years with no diphtheria- and tetanus-containing vaccine in the last 20 years. Participants received one dose of Tdap-IPV followed by two doses of Td-IPV (0, 1, 6 month schedule). Primary immunogenicity objectives: to demonstrate acceptable seroprotection rates (percentage of participants with antibody titre above threshold) post-dose 3 for diphtheria (≥ 0.1IU/mL by seroneutralization assay [SNA]); tetanus (≥ 0.1IU/mL by enzyme-linked immunosorbent assay [ELISA]); and poliomyelitis (≥ 8 1/dil by SNA); and to evaluate the percentage of participants with an antibody concentration ≥ 5EU/mL (by ELISA) for pertussis antigens post-dose 1. Seroprotection rates were acceptable if the lower limit of the 95% confidence interval (CI) was >95%. Percentage of participants with basic clinical immunity against diphtheria (≥ 0.01IU/mL) was also assessed. Safety (adverse events [AEs] and serious AEs) was assessed after each dose. Overall, 336 participants were included (mean age: 60.2 years). Post-dose 3 seroprotection rates were: diphtheria, 94.6% (CI 91.5-96.8); tetanus and poliomyelitis, 100% (CI: 98.8-100). Percentage of participants with an antibody titre ≥ 5EU/mL against pertussis antigens was ≥ 95.8% for all five pertussis components. Basic clinical immunity against diphtheria was achieved in 100% (CI: 98.8-100) of participants. AEs were reported more frequently following vaccination with Tdap-IPV (post-dose 1: 65.3%) than with Td-IPV (post-dose 2: 48.3%; post-dose 3: 50.3%). This study highlights the benefits of using Tdap-IPV followed by two doses of Td-IPV in an

  12. Immunogenicity and safety of combined adsorbed low-dose diphtheria, tetanus and inactivated poliovirus vaccine (REVAXIS (®)) versus combined diphtheria, tetanus and inactivated poliovirus vaccine (DT Polio (®)) given as a booster dose at 6 years of age.

    Science.gov (United States)

    Gajdos, Vincent; Soubeyrand, Benoit; Vidor, Emmanuel; Richard, Patrick; Boyer, Julie; Sadorge, Christine; Fiquet, Anne

    2011-05-01

    This randomized, comparative, phase-IIIb study conducted in France aimed to demonstrate whether seroprotection against diphtheria, tetanus and poliomyelitis 1 month after a single dose of REVAXIS (low-dose diphtheria) is non-inferior to seroprotection 1 month after a single dose of DT Polio (standard-dose diphtheria), both vaccines being given as a second booster to healthy children at 6 years of age. Children were randomly assigned to receive a single intramuscular dose of REVAXIS or DT Polio. Primary endpoints were the 1-month post-booster seroprotection rates for diphtheria, tetanus and poliovirus type-1, -2 and -3 antigens. Secondary endpoints were immunogenicity and safety observations. Of 788 children screened, 760 were randomized: REVAXIS group, 384 children; DT Polio group, 376 children. No relevant difference in demographic characteristics at baseline was observed between REVAXIS and DT Polio groups. Non-inferiority of REVAXIS compared with DT Polio for seroprotection was demonstrated against diphtheria (respectively 98.6% and 99.3%), tetanus (respectively 99.6% and 100%), and poliovirus antigens (100% for each types in both groups). No allergic reactions to REVAXIS were reported. A benefit/risk ratio in favor of REVAXIS was suggested by the trend towards a better tolerability of REVAXIS compared with DT Polio regarding the rate of severe solicited injection-site reactions. The results support the use of REVAXIS as a booster at 6 years of age in infants who previously received a three-dose primary series within the first 6 months of life and a first booster including diphtheria, tetanus and poliovirus vaccine(s) given before 2 years of age.

  13. Immunogenicity and safety of combined adsorbed low-dose diphtheria, tetanus and inactivated poliovirus vaccine (REVAXIS®) versus combined diphtheria, tetanus and inactivated poliovirus vaccine (DT Polio®) given as a booster dose at 6 years of age

    Science.gov (United States)

    Gajdos, Vincent; Soubeyrand, Benoit; Vidor, Emmanuel; Richard, Patrick; Boyer, Julie; Sadorge, Christine

    2011-01-01

    This randomized, comparative, phase-IIIb study conducted in France aimed to demonstrate whether seroprotection against diphtheria, tetanus and poliomyelitis 1 month after a single dose of REVAXIS (low-dose diphtheria) is non-inferior to seroprotection 1 month after a single dose of DT Polio (standard-dose diphtheria), both vaccines being given as a second booster to healthy children at 6 years of age. Children were randomly assigned to receive a single intramuscular dose of REVAXIS or DT Polio. Primary endpoints were the 1-month post-booster seroprotection rates for diphtheria, tetanus and poliovirus type-1, -2 and -3 antigens. Secondary endpoints were immunogenicity and safety observations. Of 788 children screened, 760 were randomized: REVAXIS group, 384 children; DT Polio group, 376 children. No relevant difference in demographic characteristics at baseline was observed between REVAXIS and DT Polio groups. Noninferiority of REVAXIS compared with DT Polio for seroprotection was demonstrated against diphtheria (respectively 98.6% and 99.3%), tetanus (respectively 99.6% and 100%) and poliovirus antigens (100% for each types in both groups). No allergic reactions to REVAXIS were reported. A benefit/risk ratio in favor of REVAXIS was suggested by the trend towards a better tolerability of REVAXIS compared with DT Polio regarding the rate of severe solicited injection-site reactions. The results support the use of REVAXIS as a booster at 6 years of age in infants who previously received a three-dose primary series within the first 6 months of life and a first booster including diphtheria, tetanus and poliovirus vaccine(s) given before 2 years of age. PMID:21441781

  14. Immunity against diphtheria and tetanus in human immunodeficiency virus-infected Danish men born 1950-59

    DEFF Research Database (Denmark)

    Kurtzhals, J A; Kjeldsen, K; Heron, I;

    1992-01-01

    To evaluate the possible need for vaccination against diphtheria and tetanus of patients infected with the human immunodeficiency virus (HIV), antibodies were measured in blood samples from 78 Danish HIV-infected men, born 1950-59, who could be expected to have received primary vaccination before......-positive younger men who have followed the vaccination program against tetanus prior to the HIV infection can be expected to be protected, whereas revaccination against diphtheria must be considered....... they contracted the HIV infection. No patients (95% confidence interval: 0-4) had tetanus antibodies below the protective level, whereas 24 of the 78 patients (16-33) were unprotected against diphtheria. In the background population of the same age group and sex, 5% and 10% have been found unprotected against...

  15. Immunity against diphtheria and tetanus in human immunodeficiency virus-infected Danish men born 1950-59

    DEFF Research Database (Denmark)

    Kurtzhals, J A; Kjeldsen, K; Heron, I

    1992-01-01

    To evaluate the possible need for vaccination against diphtheria and tetanus of patients infected with the human immunodeficiency virus (HIV), antibodies were measured in blood samples from 78 Danish HIV-infected men, born 1950-59, who could be expected to have received primary vaccination before...... they contracted the HIV infection. No patients (95% confidence interval: 0-4) had tetanus antibodies below the protective level, whereas 24 of the 78 patients (16-33) were unprotected against diphtheria. In the background population of the same age group and sex, 5% and 10% have been found unprotected against...... tetanus and diphtheria, respectively. No relationship between disease stages and antibody levels could be found. Neither was there any difference between patients with normal and reduced numbers of CD4+ lymphocytes. From 25 patients two blood samples were taken at an interval of at least one year. Anti-tetanus...

  16. Novel potentiometry immunoassay with amplified sensitivity for diphtheria antigen based on Nafion, colloidal Ag and polyvinyl butyral as matrixes.

    Science.gov (United States)

    Tang, Dianping; Yuan, Ruo; Chai, Yaqin; Zhang, Linyan; Zhong, Xia; Dai, Jianyuan; Liu, Yan

    2004-11-30

    A novel potentiometry immunoassay with amplified sensitivity has been developed for the detection of diphtheria antigen (Diph) via immobilizing diphtheria antibody (anti-Diph) on a platinum electrode based on Nafion, colloidal Ag (Ag), and polyvinyl butyral (PVB) as matrixes in this study. The modified procedure was further characterized by electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). The influence and factors influencing the performance of resulting immunosensor were studied in detail. The resulting immunosensor exhibited sigmoid curve with log Diph concentrations, high sensitivity (51.4 mV/decade), wide linear range from 8 to 800 ng ml(-1) with a detection limit of 1.5 ng ml(-1), rapid potentiometric response (6 months). Analytical results of clinical samples show that the developed immunoassay is comparable with the enzyme-linked immunosorbent assays (ELISAs) method, implying a promising alternative approach for detecting diphtheria antigen in the clinical diagnosis.

  17. Recent advances in recombinant protein expression by Corynebacterium, Brevibacterium, and Streptomyces: from transcription and translation regulation to secretion pathway selection.

    Science.gov (United States)

    Liu, Long; Yang, Haiquan; Shin, Hyun-Dong; Li, Jianghua; Du, Guocheng; Chen, Jian

    2013-11-01

    Gram-positive bacteria are widely used to produce recombinant proteins, amino acids, organic acids, higher alcohols, and polymers. Many proteins have been expressed in Gram-positive hosts such as Corynebacterium, Brevibacterium, and Streptomyces. The favorable and advantageous characteristics (e.g., high secretion capacity and efficient production of metabolic products) of these species have increased the biotechnological applications of bacteria. However, owing to multiplicity from genes encoding the proteins and expression hosts, the expression of recombinant proteins is limited in Gram-positive bacteria. Because there is a very recent review about protein expression in Bacillus subtilis, here we summarize recent strategies for efficient expression of recombinant proteins in the other three typical Gram-positive bacteria (Corynebacterium, Brevibacterium, and Streptomyces) and discuss future prospects. We hope that this review will contribute to the development of recombinant protein expression in Corynebacterium, Brevibacterium, and Streptomyces.

  18. Primary Immunization with a Triple Diphtheria-Tetanus-Whole Cell Pertussis Vaccine in Iranian Infants: An Analysis of Antibody Response

    Directory of Open Access Journals (Sweden)

    Zarei Saeed

    2009-06-01

    Full Text Available Universal vaccination of neonates and children against diphtheria, tetanus and pertussis has had a tremendous impact on the control of these infectious diseases worldwide. Immunization by the triple diphtheria, tetanus and whole cell pertussis vaccine (DTwP has been applied in Iran for almost 50 years. Periodic assessment of immunogenicity of this vaccine is an important aspect of successful mass vaccination programs. The present study was performed to assess the antibody response against tetanus, diphtheria and pertussis in a group of Iranian infants vaccinated with a local DTwP vaccine. In this prospective study, 330 infants received primary vaccination at 2, 4 and 6 months of age with DTwP vaccine manufactured by Razi Institute of Iran. Blood samples were taken 2-4 weeks after the third dose to assess seroprotection and geometric mean titers (GMT of specific antibodies. Among the 283 infants who completed the vaccination course, 98.2% and 100% developed antibodies against diphtheria and tetanus, respectively. The GMT of antibodies to tetanus, diphtheria and pertussis, were 2.09 IU/ml, 2.08 IU/ml and 8.73 EU/ml, respectively. Comparison of the results obtained from this study with those from previous studies performed in other countries revealed a similar GMT and protection rates for diphtheria and tetanus components. In the absence of well-established serological criteria, judgment about protection rate against pertussis has not been possible. A prospective vaccination study using the local DTwP vaccine in parallel to a WHO approved standard vaccine, could enable assessment of immunogenicity of the pertussis component.

  19. Long-Term Protection against Diphtheria in the Netherlands after 50 Years of Vaccination: Results from a Seroepidemiological Study.

    Science.gov (United States)

    Swart, E M; van Gageldonk, P G M; de Melker, H E; van der Klis, F R; Berbers, G A M; Mollema, L

    2016-01-01

    To evaluate the National Immunisation Programme (NIP) a population-based cross-sectional seroepidemiological study was performed in the Netherlands. We assessed diphtheria antitoxin levels in the general Dutch population and in low vaccination coverage (LVC) areas where a relatively high proportion of orthodox Protestants live who decline vaccination based on religious grounds. Results were compared with a nationwide seroepidemiological study performed 11 years earlier. In 2006/2007 a national serum bank was established. Blood samples were tested for diphtheria antitoxin IgG concentrations using a multiplex immunoassay for 6383 participants from the national sample (NS) and 1518 participants from LVC municipalities. A cut-off above 0.01 international units per ml (IU/ml) was used as minimum protective level. In the NS 91% of the population had antibody levels above 0.01 IU/ml compared to 88% in the 1995/1996 serosurvey (pdiphtheria vaccination in the NIP and 46% (vs. 37% in the 1995/1996 serosurvey, p = 0.11) of orthodox Protestants living in LVC areas had antibody levels above 0.01 IU/ml. Linear regression analysis among fully immunized individuals (six vaccinations) without evidence of revaccination indicated a continuous decline in antibodies in both serosurveys, but geometric mean antibodies remained well above 0.01 IU/ml in all age groups. The NIP provides long-term protection against diphtheria, although antibody levels decline after vaccination. As a result of natural waning immunity, a substantial proportion of individuals born before introduction of diphtheria vaccination in the NIP lack adequate levels of diphtheria antibodies. Susceptibility due to lack of vaccination is highest among strictly orthodox Protestants. The potential risk of spread of diphtheria within the geographically clustered orthodox Protestant community after introduction in the Netherlands has not disappeared, despite national long-term high vaccination coverage.

  20. Comparison of seven commercial enzyme-linked immunosorbent assays for the detection of anti-diphtheria toxin antibodies.

    Science.gov (United States)

    Zasada, A A; Rastawicki, W; Śmietańska, K; Rokosz, N; Jagielski, M

    2013-07-01

    Determination of immune status of patients to diphtheria toxin is based mainly on the results of commercially available ELISA kits. The aim of the present study was to compare the results obtained by ELISAs from seven different manufacturers: Mikrogen, Immunolab, Sekisui Virotech, NovaTec, Virion\\Serion, IBL International and Euroimmun. All assays were performed according to the manufacturers' instructions. The concentrations of the anti-diphtheria toxin antibodies in 72 serum samples were calculated on the basis of curves constructed from standards supplied by manufacturers and the new reference material-International Standard for Diphtheria Antitoxin (10/262). The repeatability and reproducibility of all the ELISA kits tested were good. Number of sera with concentrations of the anti-diphtheria toxin antibodies below the WHO-recommended level of protection (0.1 IU/ml) were dependent on the ELISA used: Mikrogen, 20/72 samples (27.7%); Immunolab, 11/72 samples (15.3%); Sekisui Virotech, 0/72 samples (0%); NovaTec 18/72 samples (25.0%); Serion 12/72 samples (16.7%); IBL International, 7/72 samples (9.7 %); and Euroimmun, 17/72 samples (23.6%). However, the results obtained in particular ELISAs, with the exception of Sekisui Virotech, were much more consistent when the concentrations of the anti-diphtheria toxin antibodies in 72 sera measured by using curves constructed from the International Standard 10/262. The data obtained clearly demonstrated that manufacturer-dependent differences between anti-diphtheria IgG ELISA kits exist. The differences in recommendations accepted by the individual manufacturers together with differences shown in our studies in sensitivity greatly affect the clinical interpretation of results.

  1. Evaluation of Immunogenicity of Yersinia enterocolitica O:8 Oligopolysaccaride-DiphtheriaeToxoide Conjugate in Mice

    Directory of Open Access Journals (Sweden)

    SM Rezavian

    2015-06-01

    Full Text Available Background & objectives: Yersiniosis is created by Yersinia enterocolitica O:8 and causes problems in the world especialy in cold and mild countries. The purpose of this study is to evaluate the immunogenicity of Yersinia enterocolitica O:8 oligopolysaccaride (OPS conjugate to diphtheria toxoid (DT as a vaccine candidate.   Methods : After cultivation of bacteria, the LPS were isolated by modified hot phenol method. Then dialysis and concentration were done and the OPS were extracted by acetic acid 2%. To conjugate with diphtheria toxoid, ADH was used as a spacer molecule and EDAC as a linker. Conjugate was purified by gel filtration. Then 4 groups of female BALB/c mice were selected (15 mice in each group. Injection was performed intraperitoneally in three doses with two weeks interval. Then serum samples were collected and antibody response against OPS was measured by indirect ELISA method for detection of total IgG, IgA, IgM, IgG1, IgG2a, IgG2b and IgG3.   Results: After second and third doses, OPS-DT recieved group showed significant increase in all types of antibodies titer in anti-OPS in comparison to group that recived nonconjugated OPS. The increase in titer of antibodies was as: OPS-DT>OPS>DT. A remarkable increase was shown in total IgG and IgM titers (with total amount of 3204 and 670, respectively. In IgG1 subclass the amount was 920 and in other subclasses of IgG (IgG3, IgG2a and IgG2b the amounts were 910, 110, and 99, respectively.   Conclusion: The results shows that OPS of Yersinia enterocolitica O:8 increases the anti-OPS antibodies in the form of conjugate with diphtheria toxoid and could be considered as an appropriate vaccine candidate.

  2. Risk of Febrile Seizures and Epilepsy After Vaccination With Diphtheria, Tetanus, Acellular Pertussis, Inactivated Poliovirus, and Haemophilus Influenzae Type b

    DEFF Research Database (Denmark)

    Sun, Yuelian; Christensen, Jakob Christensen; Hviid, Anders

    2012-01-01

    Context Vaccination with whole-cell pertussis vaccine carries an increased risk of febrile seizures, but whether this risk applies to the acellular pertussis vaccine is not known. In Denmark, acellular pertussis vaccine has been included in the combined diphtheria-tetanus toxoids-acellular pertus......Context Vaccination with whole-cell pertussis vaccine carries an increased risk of febrile seizures, but whether this risk applies to the acellular pertussis vaccine is not known. In Denmark, acellular pertussis vaccine has been included in the combined diphtheria-tetanus toxoids...

  3. NCBI nr-aa BLAST: CBRC-AGAM-01-0038 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-AGAM-01-0038 ref|NP_938793.1| Putative cytochrome C biogenesis protein [Corynebacterium diphtheria...e NCTC 13129] emb|CAE48916.1| Putative cytochrome C biogenesis protein [Corynebacterium diphtheriae] NP_938793.1 1.6 24% ...

  4. NCBI nr-aa BLAST: CBRC-CREM-01-1346 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-CREM-01-1346 ref|NP_939160.1| Na(+)/H(+) antiporter homolog [Corynebacterium diphtheria...e NCTC 13129] emb|CAE49312.1| Na(+)/H(+) antiporter homolog [Corynebacterium diphtheriae] NP_939160.1 2e-34 34% ...

  5. Antibody response to booster vaccination with tetanus and diphtheria in adults exposed to perfluorinated alkylates

    DEFF Research Database (Denmark)

    Kielsen, Katrine; Shamim, Zaiba; Ryder, Lars P.;

    2016-01-01

    prospectively followed for 30 days after a booster vaccination with diphtheria and tetanus. The results indicated that serum-PFAS concentrations were positively correlated and positively associated with age and male sex. The specific antibody concentrations in serum were increased from Day 4 to Day 10 post...... adjustment for sex and age. Although the study involved a small number of subjects, these findings of a PFAS-associated reduction of the early humoral immune response to booster vaccination in healthy adults supported previous findings of PFAS immunosuppression in larger cohorts. Furthermore, the results...

  6. Two cases of cutaneous diphtheria associated with occupational pig contact in Germany.

    Science.gov (United States)

    Berger, A; Boschert, V; Konrad, R; Schmidt-Wieland, T; Hörmansdorfer, S; Eddicks, M; Sing, A

    2013-12-01

    In 2010, two independent cases of cutaneous diphtheria caused by toxigenic C. ulcerans were identified in Germany. Both patients had intense occupational contact with pigs. Diagnostic work-up comprising biochemical differentiation, rpoB sequencing, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) analysis, real-time tox PCR and Elek test as well as public health measures including an intensified source tracing involving 83 asymptomatic pigs of an associated pig farm are presented. © 2012 Blackwell Verlag GmbH.

  7. Detection of diphtheria toxin antibodies in human sera in New Zealand by ELISA.

    OpenAIRE

    Lau, R. C.

    1986-01-01

    An enzyme-linked immunosorbent assay (ELISA) was developed to detect IgG antibodies to diphtheria toxin in human serum. Serum samples obtained from 557 normal persons aged 1-65 years from different areas in New Zealand showed maximum antibody levels in the 1-9 years age group (95.1%) and the least in the 60-65 years age group (38.1%). The indirect ELISA is suitable for seroepidemiological survey study as it is simple to perform, economical and precise.

  8. Antibody level of New Zealand children immunized with the triple vaccine DTP (diphtheria-tetanus-pertussis).

    OpenAIRE

    Lau, R. C.

    1988-01-01

    Enzyme-linked immunosorbent assay (ELISA) tests were used to measure IgG antibody levels in 2638 New Zealand children who had been immunized with the triple vaccine DTP. The percentage of children immune to diphtheria decreased with age. The percentage of children immune to tetanus varied from 67.1 to 55.0%. The percentage of children with measurable antibody to pertussis increased with age. The mean percentages of children with measurable antibody or immunity to one or more DTP components we...

  9. Does vaccination ensure protection? Assessing diphtheria and tetanus antibody levels in a population of healthy children: A cross-sectional study.

    Science.gov (United States)

    Gowin, Ewelina; Wysocki, Jacek; Kałużna, Ewelina; Świątek-Kościelna, Bogna; Wysocka-Leszczyńska, Joanna; Michalak, Michał; Januszkiewicz-Lewandowska, Danuta

    2016-12-01

    Vaccination effectiveness is proven when the disease does not develop after a patient is exposed to the pathogen. In the case of rare diseases, vaccination effectiveness is assessed by monitoring specific antibody levels in the population. Such recurrent analyses allow the evaluation of vaccination programs. The primary schedule of diphtheria and tetanus vaccinations is similar in various countries, with differences mainly in the number and timing of booster doses. The aim of the study was to assess diphtheria and tetanus antibody concentrations in a population of healthy children.Diphtheria and tetanus antibody levels were analyzed in a group of 324 children aged 18 to 180 months. All children were vaccinated in accordance with the Polish vaccination schedule.Specific antibody concentrations greater than 0.1 IU/mL were considered protective against tetanus or diphtheria. Levels above 1.0 were considered to ensure long-term protection.Protective levels of diphtheria antibodies were found in 229 patients (70.46%), and of tetanus in 306 patients (94.15%). Statistically significant differences were found in tetanus antibody levels in different age groups. Mean concentrations and the percentage of children with high tetanus antibody titers increased with age. No similar correlation was found for diphtheria antibodies. High diphtheria antibody levels co-occurred in 72% of the children with high tetanus antibody levels; 95% of the children with low tetanus antibody levels had low levels of diphtheria antibodies.The percentage of children with protective diphtheria antibody levels is lower than that in the case of tetanus antibodies, both in Poland and abroad, but the high proportion of children without diphtheria protection in Poland is an exception. This is all the more puzzling when taking into account that Polish children are administered a total of 5 doses containing a high concentration of diphtheria toxoid, at intervals shorter than 5 years. The decrease in

  10. Recurrent Breast Abscesses due to Corynebacterium kroppenstedtii, a Human Pathogen Uncommon in Caucasian Women

    Directory of Open Access Journals (Sweden)

    Anne Le Flèche-Matéos

    2012-01-01

    Full Text Available Background. Corynebacterium kroppenstedtii (Ck was first described in 1998 from human sputum. Contrary to what is observed in ethnic groups such as Maori, Ck is rarely isolated from breast abscesses and granulomatous mastitis in Caucasian women. Case Presentation. We herein report a case of recurrent breast abscesses in a 46-year-old Caucasian woman. Conclusion. In the case of recurrent breast abscesses, even in Caucasian women, the possible involvement of Ck should be investigated. The current lack of such investigations, probably due to the difficulty to detect Ck, may cause the underestimation of such an aetiology.

  11. Purification of a cytochrome bc1-aa3 supercomplex with quinol oxidase activity from Corynebacterium glutamicum

    OpenAIRE

    Niebisch, A.; Bott, M.

    2003-01-01

    The aerobic respiratory chain of the Gram-positive Corynebacterium glutamicum involves a bc(1) complex with a diheme cytochrome c(1) and a cytochrome aa(3) oxidase but no additional c-type cytochromes. Here we show that the two enzymes form a supercomplex, because affinity chromatography of either strep-tagged cytochrome b (QcrB) or strep-tagged subunit I (CtaD) of cytochrome aa(3) always resulted in the copurification of the subunits of the bc(1) complex (QcrA, QcrB, QcrC) and the aa(3) comp...

  12. APLICACION DE TECNICAS DE INGENIERIA METABOLICA AL MEJORAMIENTO DE LA PRODUCCION DE TREHALOSA POR CORYNEBACTERIUM GLUTAMICUM.

    OpenAIRE

    PADILLA IGLESIAS, LEANDRO MAURICIO

    2004-01-01

    La Trehalosa es un disacárido con tremendas aplicaciones en la industria biotecnológica y alimenticia. Este compuesto se encuentra en muchos organismos, a causa de su capacidad de proteger las células contra el calor y la deshidratación. Un ejemplo, es la bacteria Gram-positiva Corynebacterium glutamicum, la cual sintetiza trehalosa a través de dos rutas principales, TreYZ y OtsBA, usando ADP-glucosa (especulativamente) y UDP-glucosa, respectivamente, como dadores de unidades de ...

  13. Recent progress in development of synthetic biology platforms and metabolic engineering of Corynebacterium glutamicum.

    Science.gov (United States)

    Woo, Han Min; Park, Jin-Byung

    2014-06-20

    The paradigm of synthetic biology has been evolving, along with relevant engineering, to achieve designed bio-systems. Synthetic biology has reached the point where it is possible to develop microbial strains to produce desired chemicals. Recent advances in this field have promoted metabolic engineering of Corynebacterium glutamicum as an amino-acid producer for use in intelligent microbial-cell factories. Here, we review recent advances that address C. glutamicum as a potential model organism for synthetic biology, and evaluate their industrial applications. Finally, we highlight the perspective of developing C. glutamicum as a step toward advanced microbial-cell factories that could produce valuable chemicals from renewable resources.

  14. An observational study of Corynebacterium bovis in selected Ontario dairy herds.

    OpenAIRE

    1983-01-01

    An observational study of Corynebacterium bovis was conducted in 74 Ontario dairy herds. The levels of infection with C. bovis were 19.9, 36.2 and 85.6% at the quarter, cow and herd level, respectively. Teat disinfection was found to be the variable best able to distinguish between herds with a high or low C. bovis quarter infection rate. Mean total milk somatic cell counts for 1103 quarters and 107 cows infected with only C. bovis ranged between 150,000 and 200,000/mL and were significantly ...

  15. Recombinant cholera toxin B subunit (rCTB) as a mucosal adjuvant enhances induction of diphtheria and tetanus antitoxin antibodies in mice by intranasal administration with diphtheria-pertussis-tetanus (DPT) combination vaccine.

    Science.gov (United States)

    Isaka, Masanori; Komiya, Takako; Takahashi, Motohide; Yasuda, Yoko; Taniguchi, Tooru; Zhao, Yanqiu; Matano, Keiko; Matsui, Hideyuki; Maeyama, Jun-Ichi; Morokuma, Kazunori; Ohkuma, Kunio; Goto, Norihisa; Tochikubo, Kunio

    2004-08-13

    Recombinant cholera toxin B subunit (rCTB) which is produced by Bacillus brevis carrying pNU212-CTB acts as a mucosal adjuvant capable of enhancing host immune responses specific to unrelated, mucosally co-administered vaccine antigens. When mice were administered intranasally with diphtheria-pertussis-tetanus (DPT) combination vaccine consisting of diphtheria toxoid (DTd), tetanus toxoid (TTd), pertussis toxoid (PTd), and formalin-treated filamentous hemagglutinin (fFHA), the presence of rCTB elevated constantly high values of DTd- and TTd-specific serum ELISA IgG antibody titres, and protective levels of diphtheria and tetanus toxin-neutralizing antibodies but the absence of rCTB did not. Moreover, the addition of rCTB protected all mice against tetanic symptoms and deaths. DPT combination vaccine raised high levels of serum anti-PT IgG antibody titres regardless of rCTB and protected mice from Bordetella pertussis challenge. These results suggest that co-administration of rCTB as an adjuvant is necessary for induction of diphtheria and tetanus antitoxin antibodies on the occasion of intranasal administration of DPT combination vaccine.

  16. Depletion of alveolar macrophages in CD11c diphtheria toxin receptor mice produces an inflammatory response

    Science.gov (United States)

    Roberts, Lydia M; Ledvina, Hannah E; Tuladhar, Shraddha; Rana, Deepa; Steele, Shaun P; Sempowski, Gregory D; Frelinger, Jeffrey A

    2015-01-01

    Alveolar macrophages play a critical role in initiating the immune response to inhaled pathogens and have been shown to be the first cell type infected following intranasal inoculation with several pathogens, including Francisella tularensis. In an attempt to further dissect the role of alveolar macrophages in the immune response to Francisella, we selectively depleted alveolar macrophages using CD11c.DOG mice. CD11c.DOG mice express the diphtheria toxin receptor (DTR) under control of the full CD11c promoter. Because mice do not express DTR, tissue restricted expression of the primate DTR followed by treatment with diphtheria toxin (DT) has been widely used as a tool in immunology to examine the effect of acute depletion of a specific immune subset following normal development. We successfully depleted alveolar macrophages via intranasal administration of DT. However, alveolar macrophage depletion was accompanied by many other changes to the cellular composition and cytokine/chemokine milieu in the lung that potentially impact innate and adaptive immune responses. Importantly, we observed a transient influx of neutrophils in the lung and spleen. Our experience serves as a cautionary note to other researchers using DTR mice given the complex changes that occur following DT treatment that must be taken into account when analyzing data. PMID:26029367

  17. Dmp1 Promoter-Driven Diphtheria Toxin Receptor Transgene Expression Directs Unforeseen Effects in Multiple Tissues

    Directory of Open Access Journals (Sweden)

    Ahmed Al-Jazzar

    2016-12-01

    Full Text Available Mice harbouring a dentin matrix protein 1 (Dmp1 promoter-driven human diphtheria toxin (DT receptor (HDTR transgene (Tg have recently been used to attain targeted ablation of osteocytes by diphtheria toxin (DT treatment in order to define osteocyte function. Use of these Tg mice has asserted mechano- and novel paracrine regulatory osteocyte functions. To explore osteocyte roles fully, we sought to confirm the selectivity of DT effects in these transgenic mice. However, our findings revealed incomplete DT-induced osteocyte ablation, prevalent HDTR misexpression, as well as more prominent histopathological DT-induced changes in multiple organs in Tg than in wild-type (WT littermate mice. Mechanistic evidence for DT action, via prominent regulation of phosphorylation status of elongation factor-2 (EF-2, was also found in many non-skeletal tissues in Tg mice; indicative of direct “off-target” DT action. Finally, very rapid deterioration in health and welfare status in response to DT treatment was observed in these Tg when compared to WT control mice. Together, these data lead us to conclude that alternative models for osteocyte ablation should be sought and caution be exercised when drawing conclusions from experiments using these Tg mice alone.

  18. Immunity to diphtheria in children three-to-six year of age in four counties of Taiwan.

    Science.gov (United States)

    Lee, H F; Wang, M C; Tseng, L R; Lu, C F; Hsu, H M; Horng, C B

    1995-02-01

    An immunization program against diphtheria has been implemented in Taiwan since 1955, using combined diphtheria, pertussis and tetanus (DPT) vaccine. Diphtheria immunoglobulin (DIG) level was assessed in serum samples obtained from 1138 children, aged 3-6 years from north, south, east and central part of Taiwan by the VERO cell neutralization method. Specimens were collected by simple random sampling of residents from Hsinchu, Taichung, Pingtung and Hwalien counties, including both aborigines and non-aborigines. The former lived in one or two villages in each county, and the latter lived in a single village next to the former. Ninety-five percent (1086/1138) had a DIG titre > or = 0.01 IU/ml. There was no significant difference by sex, or by residential area. Seventy-nine percent (901/1138) of the children had completed the primary immunization schedule (at the age of 2, 4, 6 and 18 months), and the prevalence of DIG titre > or = 0.1 IU/ml considered to be long-term protective was as follows: 74.6% for 3-year group; 74.5% for 4-year group; 67.9% for 5-year group; 84.7% for 6-year group (including 52.2% who had had a booster shot at early primary school). These findings show that the diphtheria vaccination program provides good immunity in childhood.

  19. Persistence of antibodies 3 years after booster vaccination of adults with combined acellular pertussis, diphtheria and tetanus toxoids vaccine.

    Science.gov (United States)

    Weston, Wayde; Messier, Marc; Friedland, Leonard R; Wu, Xiangfeng; Howe, Barbara

    2011-11-01

    The duration of protection after vaccination with reduced antigen content diphtheria, tetanus and acellular pertussis vaccines (Tdap) is not known. Long-term post-vaccination serological data will help to improve understanding of the duration of humoral immunity and guide vaccination policy for the timing of repeat dose administration. The persistence of antibodies to Tdap antigens was measured 3 years after vaccination of adults 19-64 years of age with one of 2 Tdap vaccines (Boostrix(®), GlaxoSmithKline Biologicals; Tdap-B: or Adacel(®), Sanofi Pasteur; Tdap-A). In both groups, geometric mean concentrations for antibodies to diphtheria, tetanus, and pertussis vaccine antigens were decreased at year 3 relative to levels observed 1 month and 1 year following vaccination, but remained higher than pre-vaccination levels. Seroprotection rates for diphtheria and tetanus remained high for both Tdap vaccines (for diphtheria, 96.9% and 97.8% for the Tdap-B and Tdap-A groups, respectively; for tetanus, 98.1% and 99.6%, respectively).

  20. Diphtheria toxoid-containing microparticulate powder formulations for pulmonary vaccination : Preparation, characterization and evaluation in guinea pigs

    NARCIS (Netherlands)

    Amidi, Maryam; Pellikaan, Hubert C.; Hirschberg, Hoang; de Boerd, Anne H.; Crommelin, Daan J. A.; Hennink, Wim E.; Kersten, Gideon; Jiskoot, Wim

    2007-01-01

    this study, the potential of N-Trimethyl chitosan (TMC, degree of quaternization 50%) and dextran microparticles for pulmonary delivery of diphtheria toxoid (DT) was investigated. The antigen-containing microparticles were prepared by drying of an aqueous solution of polymer and DT through a supercr

  1. Evaluation and validation of a single-dilution potency assay based upon serology of vaccines containing diphtheria toxoid: statistical analysis

    NARCIS (Netherlands)

    Marsman FR; Akkermans AM; Hendriksen CFM; de Jong WH

    1993-01-01

    This document presents the results of a validation study to the use of a single dilution assay in potency testing of the diphtheria component of DPT-polio vaccines. Based on historical data of multi-dilution assays on 27 consecutive batches a simulation study was performed to test the actual perfor

  2. Diphtheria toxoid-containing microparticulate powder formulations for pulmonary vaccination : Preparation, characterization and evaluation in guinea pigs

    NARCIS (Netherlands)

    Amidi, Maryam; Pellikaan, Hubert C.; Hirschberg, Hoang; de Boerd, Anne H.; Crommelin, Daan J. A.; Hennink, Wim E.; Kersten, Gideon; Jiskoot, Wim

    2007-01-01

    this study, the potential of N-Trimethyl chitosan (TMC, degree of quaternization 50%) and dextran microparticles for pulmonary delivery of diphtheria toxoid (DT) was investigated. The antigen-containing microparticles were prepared by drying of an aqueous solution of polymer and DT through a supercr

  3. The Introduction of Diphtheria-Tetanus-Pertussis and Oral Polio Vaccine Among Young Infants in an Urban African Community

    DEFF Research Database (Denmark)

    Mogensen, Søren Wengel; Andersen, Andreas; Rodrigues, Amabelia

    2017-01-01

    Background We examined the introduction of diphtheria-tetanus-pertussis (DTP) and oral polio vaccine (OPV) in an urban community in Guinea-Bissau in the early 1980s. Methods The child population had been followed with 3-monthly nutritional weighing sessions since 1978. From June 1981 DTP and OPV...

  4. No influence of atopic diseases on antibody titres following tetanus, diphtheria and hepatitis B immunisation among adults.

    Science.gov (United States)

    Friedrich, N; Kramer, A; Mentel, R; Gürtler, L; John, U; Völzke, H

    2007-12-01

    Several studies have reported associations between reduced humoral immune response to vaccine antigens and diseases with modified reactions of the immune system. We have investigated the influence of atopic diseases on specific IgG levels to tetanus, diphtheria and hepatitis B (HB), following immunisation, in a general adult population. From the Study of Health in Pomerania, a total number of 3,920 subjects aged 20 to 79 years were included in the analyses. Information on immunisation history, as well as behavioural and socio-demographic characteristics were collected. Anti-tetanus IgG, anti-diphtheria IgG and anti-HBs IgG were measured by indirect enzyme-linked immunosorbent assay (ELISA). Odds ratios and 95% confidence intervals were calculated using logistic regression. Atopic diseases were reported by 14% of participants. Proportions of 67%, 34% and 10% had been vaccinated against tetanus, diphtheria and hepatitis B within the past ten years, respectively. Multi-variable analyses revealed no associations between the presence of atopic diseases and all of the three vaccine-specific antibody titres. We conclude that there is no reduced immune response related to antibody production following immunisations against tetanus, diphtheria and hepatitis B in adults with atopic diseases.

  5. Genome sequence of Corynebacterium pseudotuberculosis biovar equi strain 258 and prediction of antigenic targets to improve biotechnological vaccine production

    DEFF Research Database (Denmark)

    Soares, Siomar C; Trost, Eva; Ramos, Rommel T J;

    2013-01-01

    Corynebacterium pseudotuberculosis is the causative agent of several veterinary diseases in a broad range of economically important hosts, which can vary from caseous lymphadenitis in sheep and goats (biovar ovis) to ulcerative lymphangitis in cattle and horses (biovar equi). Existing vaccines ag...

  6. Draft Genome Sequence of Corynebacterium variabile Mu292, Isolated from Munster, a French Smear-Ripened Cheese

    OpenAIRE

    Dugat-Bony, Eric; Sarthou, Anne-Sophie; Loux, Valentin; Vidal, Marie; Bonnarme, Pascal; Irlinger, Françoise; Layec, Séverine

    2016-01-01

    Here, we report the draft genome sequence of Corynebacterium variabile Mu292, which was originally isolated from the surface of Munster, a French smear-ripened cheese. This genome investigation will improve our knowledge on the molecular determinants potentially involved in the adaptation of this strain during the Munster-type cheese manufacturing process.

  7. Corynebacterium uropygiale sp. nov., isolated from the preen gland of Turkeys (Meleagris gallopavo).

    Science.gov (United States)

    Braun, Markus Santhosh; Zimmermann, Stefan; Danner, Maria; Rashid, Harun-or; Wink, Michael

    2016-03-01

    A novel species of fastidious, lipophilic, club-shaped, Gram-positive bacteria was recovered from the preen glands of healthy Turkeys (Meleagris gallopavo) from two different locations. Phylogenetic analysis of the 16S rRNA gene showed highest similarity to Corynebacterium spheniscorum DSM 44757(T) (96.8%) with a 3.2kb stretch of rpoB sharing 82.4% sequence similarity to the same species. DNA fingerprinting by ERIC-PCR and polar lipid profiles clearly differentiated the Turkey isolates from the most closely related Corynebacteria, as did MALDI-TOF MS analysis. Chemotaxonomic tests revealed the presence of corynemycolic acids with C16:0, C18:0, C18:1ω9c and tuberculostearic acid as the major cellular fatty acids. The G+C content of the type strain was 60.7 mol%. The species was susceptible to ampicillin, kanamycin A, streptomycin, amikacin, polymyxin B and vancomycin. From our results, it becomes evident that the isolated organisms represent a new species, for which the name Corynebacterium uropygiale sp. nov. is proposed. The type strain is Iso10(T) (=DSM 46817(T)=LMG 28616(T)).

  8. First report of Corynebacterium pseudotuberculosis from caseous lymphadenitis lesions in Black Alentejano pig (Sus scrofa domesticus).

    Science.gov (United States)

    Oliveira, Manuela; Barroco, Cynthia; Mottola, Carla; Santos, Raquel; Lemsaddek, Abdelhak; Tavares, Luis; Semedo-Lemsaddek, Teresa

    2014-09-21

    Corynebacterium pseudotuberculosis is the etiologic agent of caseous lymphadenitis, a common disease in small ruminant populations throughout the world and responsible for a significant economic impact for producers. To our knowledge, this is the first characterization of C. pseudotuberculosis from caseous lymphadenitis lesions in Black Alentejano pig (Sus scrofa domesticus). In this study, phenotypic and genotypic identification methods allocated the swine isolates in C. pseudotuberculosis biovar ovis. The vast majority of the isolates were able to produce phospholipase D and were susceptible to most of the antimicrobial compounds tested. Macrorestriction patterns obtained by Pulsed Field Gel Electrophoresis (PFGE) grouped the C. pseudotuberculosis in two clusters with a high similarity index, which reveals their clonal relatedness. Furthermore, swine isolates were compared with C. pseudotuberculosis from caprines and PFGE patterns also showed high similarity, suggesting the prevalence of dominant clones and a potential cross-dissemination between these two animal hosts. This work represents the first report of Corynebacterium pseudotuberculosis from caseous lymphadenitis lesions in Black Alentejano pig and alerts for the importance of the establishment of suitable control and sanitary management practices to control the infection and avoid further dissemination of this important pathogen to other animal hosts.

  9. Utilization of soluble starch by a recombinant Corynebacterium glutamicum strain: growth and lysine production.

    Science.gov (United States)

    Seibold, Gerd; Auchter, Marc; Berens, Stephan; Kalinowski, Jörn; Eikmanns, Bernhard J

    2006-07-13

    Corynebacterium glutamicum, well known for the industrial production of amino acids, grows aerobically on a variety of mono- and disaccharides and on alcohols and organic acids as single or combined sources of carbon and energy. Members of the genera Corynebacterium and Brevibacterium were here tested for their ability to use the homopolysaccharide starch as a substrate for growth. None of the 24 type strains tested showed growth on or degradation of this substrate, indicating that none of the strains synthesized and secreted starch-degrading enzymes. Introducing the Streptomyces griseus amy gene on an expression vector into the lysine-producer C. glutamicum DM1730, we constructed a C. glutamicum strain synthesizing and secreting alpha-amylase into the culture broth. Although some high-molecular-weight degradation products remained in the culture broth, this recombinant strain effectively used soluble starch as carbon and energy substrate for growth and also for lysine production. Thus, employment of our construct allows avoidance of the cost-intensive enzymatic hydrolysis of the starch, which commercially is used as a substrate in industrial amino acid fermentations.

  10. Growth characteristics of Brevibacterium, Corynebacterium, Microbacterium, and Staphylococcus spp. isolated from surface-ripened cheese.

    Science.gov (United States)

    Mounier, Jérôme; Rea, Mary C; O'Connor, Paula M; Fitzgerald, Gerald F; Cogan, Timothy M

    2007-12-01

    The growth characteristics of five bacteria, Brevibacterium aurantiacum 1-16-58, Corynebacterium casei DPC 5298(T), Corynebacterium variabile DPC 5310, Microbacterium gubbeenense DPC 5286(T), and Staphylococcus saprophyticus 4E61, all of which were isolated from the surface of smear cheese, were studied in complex and chemically defined media. All of the coryneforms, except M. gubbeenense, grew in 12% salt, while B. aurantiacum and S. saprophyticus grew in 15% salt. All five bacteria assimilated lactate in a semisynthetic medium, and none of the coryneform bacteria assimilated lactose. Glucose assimilation was poor, except by S. saprophyticus and C. casei. Five to seven amino acids were assimilated by the coryneforms and 12 by S. saprophyticus. Glutamate, phenylalanine, and proline were utilized by all five bacteria, whereas utilization of serine, threonine, aspartate, histidine, alanine, arginine, leucine, isoleucine, and glycine depended on the organism. Growth of C. casei restarted after addition of glutamate, proline, serine, and lactate at the end of the exponential phase, indicating that these amino acids and lactate can be used as energy sources. Pantothenic acid was essential for the growth of C. casei and M. gubbeenense. Omission of biotin reduced the growth of B. aurantiacum, C. casei, and M. gubbeenense. All of the bacteria contained lactate dehydrogenase activity (with both pyruvate and lactate as substrates) and glutamate pyruvate transaminase activity but not urease activity.

  11. Desulfurization of dibenzothiophene by a newly isolated Corynebacterium sp.ZD-1 in aqueous phase

    Institute of Scientific and Technical Information of China (English)

    WANG Miao-dong; LI Wei; WANG Da-hui; SHI Yao

    2004-01-01

    Sulfur emission through fuel combustion is a global problem because it is a major cause of acid rain. Crud oil contains many heterocyclic organic sulfur compounds, among which dibenzothiophene(DBT) and DBTs bearing alkyl substitutions usually are representative compounds. A strain was isolated from refinery sludge and identified as Corynebacterium ZD-1. The behavior of DBT degradation by ZD-1 in aqueous phase was investigated. Corynebacterium ZD-1 could metabolize DBT to 2-hydroxybiphenyl(2-HBP) as the dead-end metabolite through a sulfur-specific pathway. In shake flask culture, ZD-1 had its maximal desulfurization activity in the late exponential growth phase and the specific production rate of 2-HBP was about 0.14(mmol·kg dry cell-1·min-1, mmol·KDC-1·min-1). Active resting cells for desulfurization should be prepared only in this period. 2-HBP inhibited the growth of strain ZD-1, the production of DBT degradation enzymes, and the activity of enzymes. Sulfate inhibited the production of dibenzothiophene(DBT) degradation enzymes but had no effect on the enzymes' activity. The production rates of 2-HBP at lower cell densities were higher and the maximum amount conversion of DBT to 2-HBP(0.067 mmol/L) after 8 h was gained at 9.2(g dry cell/L) rather higher cell density. The results indicated that this newly isolated strain could be a promising biocatalyst for DBT desulfurization.

  12. Long-Term Protection against Diphtheria in the Netherlands after 50 Years of Vaccination: Results from a Seroepidemiological Study.

    Directory of Open Access Journals (Sweden)

    E M Swart

    Full Text Available To evaluate the National Immunisation Programme (NIP a population-based cross-sectional seroepidemiological study was performed in the Netherlands. We assessed diphtheria antitoxin levels in the general Dutch population and in low vaccination coverage (LVC areas where a relatively high proportion of orthodox Protestants live who decline vaccination based on religious grounds. Results were compared with a nationwide seroepidemiological study performed 11 years earlier.In 2006/2007 a national serum bank was established. Blood samples were tested for diphtheria antitoxin IgG concentrations using a multiplex immunoassay for 6383 participants from the national sample (NS and 1518 participants from LVC municipalities. A cut-off above 0.01 international units per ml (IU/ml was used as minimum protective level.In the NS 91% of the population had antibody levels above 0.01 IU/ml compared to 88% in the 1995/1996 serosurvey (p<0.05. On average, 82% (vs. 78% in the 1995/1996 serosurvey, p<0.05 of individuals from the NS born before introduction of diphtheria vaccination in the NIP and 46% (vs. 37% in the 1995/1996 serosurvey, p = 0.11 of orthodox Protestants living in LVC areas had antibody levels above 0.01 IU/ml. Linear regression analysis among fully immunized individuals (six vaccinations without evidence of revaccination indicated a continuous decline in antibodies in both serosurveys, but geometric mean antibodies remained well above 0.01 IU/ml in all age groups.The NIP provides long-term protection against diphtheria, although antibody levels decline after vaccination. As a result of natural waning immunity, a substantial proportion of individuals born before introduction of diphtheria vaccination in the NIP lack adequate levels of diphtheria antibodies. Susceptibility due to lack of vaccination is highest among strictly orthodox Protestants. The potential risk of spread of diphtheria within the geographically clustered orthodox Protestant community

  13. Antibody levels to tetanus, diphtheria, measles and varicella in patients with primary immunodeficiency undergoing intravenous immunoglobulin therapy: a prospective study.

    Science.gov (United States)

    Nobre, Fernanda Aimée; Gonzalez, Isabela Garrido da Silva; Simão, Raquel Maria; de Moraes Pinto, Maria Isabel; Costa-Carvalho, Beatriz Tavares

    2014-06-21

    Patients with antibody deficiencies depend on the presence of a variety of antibody specificities in intravenous immunoglobulin (IVIG) to ensure continued protection against pathogens. Few studies have examined levels of antibodies to specific pathogens in IVIG preparations and little is known about the specific antibody levels in patients under regular IVIG treatment. The current study determined the range of antibodies to tetanus, diphtheria, measles and varicella in IVIG products and the levels of these antibodies in patients undergoing IVIG treatment. We selected 21 patients with primary antibody deficiencies who were receiving regular therapy with IVIG. Over a period of one year, we collected four blood samples from each patient (every 3 months), immediately before immunoglobulin infusion. We also collected samples from the IVIG preparation the patients received the month prior to blood collection. Antibody levels to tetanus, diphtheria, measles and varicella virus were measured in plasma and IVIG samples. Total IgG levels were determined in plasma samples. Antibody levels to tetanus, diphtheria, varicella virus and measles showed considerable variation in different IVIG lots, but they were similar when compared between commercial preparations. All patients presented with protective levels of antibodies specific for tetanus, measles and varicella. Some patients had suboptimal diphtheria antibody levels. There was a significant correlation between serum and IVIG antibodies to all pathogens, except tetanus. There was a significant correlation between diphtheria and varicella antibodies with total IgG levels, but there was no significant correlation with antibodies to tetanus or measles. The study confirmed the variation in specific antibody levels between batches of the same brand of IVIG. Apart from the most common infections to which these patients are susceptible, health care providers must be aware of other vaccine preventable diseases, which still exist

  14. Diphtheria toxin IgG levels in military and civilian blood donors in Rio de Janeiro, Brazil

    Directory of Open Access Journals (Sweden)

    F.A.B. Speranza

    2010-01-01

    Full Text Available Serologic data on diseases that are preventable by vaccines are necessary to evaluate the success of immunization programs and to identify susceptible subgroups. In the present study, we determined serum IgG levels against diphtheria toxin of military and civilian blood donors (N = 75; 69.3% males and 30.7% females aged 18-64 years, from the Brazilian Army Biology Institute, Rio de Janeiro, using a commercial diphtheria kit (Diphtheria IgG ELISA; IBL, Germany. Most (63% unprotected military donors were from the older age group of 41 to 64 years. In contrast, the majority (71% of young military donors (18 to 30 years were fully protected. About half of the military donors aged 31 to 40 years were protected against diphtheria. Among the civilians, about 50% of persons aged 18 to 30 years and 31 to 40 years had protective antibody levels against diphtheria as also did 64% of individuals aged 41 to 64 years. All civilians had a similar antibody response (geometric mean = 0.55 IU/mL independent of age group. Military donors aged 18-30 years had higher IgG levels (geometric mean = 0.82 IU/mL than military donors of 41-64 years (geometric mean = 0.51 IU/mL; P > 0.05. In conclusion, the existence of a considerable proportion of susceptible adults supports the position that reliable data on the immune status of the population should be maintained routinely and emphasizes the importance of adequate immunization during adulthood.

  15. Diphtheria toxin IgG levels in military and civilian blood donors in Rio de Janeiro, Brazil.

    Science.gov (United States)

    Speranza, F A B; Ishii, S K; Hirata, R; Mattos-Guaraldi, A L; Milagres, L G

    2010-01-01

    Serologic data on diseases that are preventable by vaccines are necessary to evaluate the success of immunization programs and to identify susceptible subgroups. In the present study, we determined serum IgG levels against diphtheria toxin of military and civilian blood donors (N = 75; 69.3% males and 30.7% females) aged 18-64 years, from the Brazilian Army Biology Institute, Rio de Janeiro, using a commercial diphtheria kit (Diphtheria IgG ELISA; IBL, Germany). Most (63%) unprotected military donors were from the older age group of 41 to 64 years. In contrast, the majority (71%) of young military donors (18 to 30 years) were fully protected. About half of the military donors aged 31 to 40 years were protected against diphtheria. Among the civilians, about 50% of persons aged 18 to 30 years and 31 to 40 years had protective antibody levels against diphtheria as also did 64% of individuals aged 41 to 64 years. All civilians had a similar antibody response (geometric mean = 0.55 IU/mL) independent of age group. Military donors aged 18-30 years had higher IgG levels (geometric mean = 0.82 IU/mL) than military donors of 41-64 years (geometric mean = 0.51 IU/mL; P > 0.05). In conclusion, the existence of a considerable proportion of susceptible adults supports the position that reliable data on the immune status of the population should be maintained routinely and emphasizes the importance of adequate immunization during adulthood.

  16. Teste de pele em caprinos vacinados e infectados com Corynebacterium pseudotuberculosis Skin test of goats vaccinated and infected with Corynebacterium pseudotuberculosis

    Directory of Open Access Journals (Sweden)

    Francisco Selmo Fernandes Alves

    1999-07-01

    Full Text Available Dez caprinos foram vacinados com toxóide a 3%, outros dez com uma bacterina e mais dois grupos-controle de cinco animais cada, submetidos à inoculação de infusão de cérebro e coração e solução salina, respectivamente. Todos os animais foram examinados e avaliados com um teste de pele. Tanto o toxóide quanto a bacterina foram produzidos a partir de amostra de Corynebacterium pseudotuberculosis. Todos os caprinos foram desafiados com C. pseudotuberculosis, trinta dias após as vacinações. Nenhuma das vacinas induziu reação de hipersensibilidade na pele dos caprinos antes do desafio. Após o desafio, todos os animais desenvolveram reações mensuráveis na primeira, quinta e décima semana em resposta ao teste de pele. Os diâmetros da reação dérmica aumentaram do décimo dia à quinta semana após o desafio. As medidas alcançaram tamanho maior na décima semana. O resultado deste estudo indica que antígeno específico do C. pseudotuberculosis pode ser utilizado em caprinos no diagnóstico da linfadenite caseosa como teste de pele ou como instrumento experimental para monitorar o desenvolvimento da doença.Ten goats were vaccinated with a 3% toxoid, ten vaccinated with a bacterin and two control groups (five animals each inoculated with brain heart infusion and saline solution, respectively. All animals were skin tested with a crude antigen of formalin-killed Corynebacterium pseudotuberculosis bacterial cells. All goats were challenged with a virulent C. pseudotuberculosis thirty days after vaccination. Neither the vaccinated nor control goats responded to the skin test prior to infection. After the challenge, dermal reactions were demonstrated in all animals at one week, five and ten weeks. The diameters increased from the first week, five and ten weeks. The reactions were more proeminent at ten weeks. The results of this study indicate that skin testing with a specific bacterial antigen of C. pseudotuberculosis may be useful

  17. The pan-genome of the animal pathogen Corynebacterium pseudotuberculosis reveals differences in genome plasticity between the biovar ovis and equi strains

    DEFF Research Database (Denmark)

    Soares, Siomar C; Silva, Artur; Trost, Eva

    2013-01-01

    Corynebacterium pseudotuberculosis is a facultative intracellular pathogen and the causative agent of several infectious and contagious chronic diseases, including caseous lymphadenitis, ulcerative lymphangitis, mastitis, and edematous skin disease, in a broad spectrum of hosts. In addition, Cory...

  18. The effect of prophylaxis with chloroquine and proguanil on delayed-type hypersensitivity and antibody production following vaccination with diphtheria, tetanus, polio, and pneumococcal vaccines

    DEFF Research Database (Denmark)

    Gyhrs, A; Pedersen, B K; Bygbjerg, I;

    1991-01-01

    (1,000 mg/week), or 4) proguanil hydrochloride (200 mg/day) for six weeks. Skin testing was performed on days 0 and 28. Vaccinations with diphtheria, tetanus, polio, and pneumococcal polysaccharide antigen vaccines were performed on day 28, and the presence of specific antibodies was determined...... dosages, does not induce any detectable suppression of delayed-type hypersensitivity or vaccination responses to diphtheria, tetanus, polio, or pneumococcal polysaccharide antigens....

  19. Determination of low tetanus or diphtheria antitoxin titers in sera by a toxin neutralization assay and a modified toxin-binding inhibition test

    Directory of Open Access Journals (Sweden)

    M.H. Sonobe

    2007-01-01

    Full Text Available A method for the screening of tetanus and diphtheria antibodies in serum using anatoxin (inactivated toxin instead of toxin was developed as an alternative to the in vivo toxin neutralization assay based on the toxin-binding inhibition test (TOBI test. In this study, the serum titers (values between 1.0 and 19.5 IU measured by a modified TOBI test (Modi-TOBI test and toxin neutralization assays were correlated (P < 0.0001. Titers of tetanus or diphtheria antibodies were evaluated in serum samples from guinea pigs immunized with tetanus toxoid, diphtheria-tetanus or triple vaccine. For the Modi-TOBI test, after blocking the microtiter plates, standard tetanus or diphtheria antitoxin and different concentrations of guinea pig sera were incubated with the respective anatoxin. Twelve hours later, these samples were transferred to a plate previously coated with tetanus or diphtheria antitoxin to bind the remaining anatoxin. The anatoxin was then detected using a peroxidase-labeled tetanus or diphtheria antitoxin. Serum titers were calculated using a linear regression plot of the results for the corresponding standard antitoxin. For the toxin neutralization assay, L+/10/50 doses of either toxin combined with different concentrations of serum samples were inoculated into mice for anti-tetanus detection, or in guinea pigs for anti-diphtheria detection. Both assays were suitable for determining wide ranges of antitoxin levels. The linear regression plots showed high correlation coefficients for tetanus (r² = 0.95, P < 0.0001 and for diphtheria (r² = 0.93, P < 0.0001 between the in vitro and the in vivo assays. The standardized method is appropriate for evaluating titers of neutralizing antibodies, thus permitting the in vitro control of serum antitoxin levels.

  20. Measuring Immunoglobulin G Antibodies to Tetanus Toxin, Diphtheria Toxin, and Pertussis Toxin with Single-Antigen Enzyme-Linked Immunosorbent Assays and a Bead-Based Multiplex Assay▿

    OpenAIRE

    Reder, Sabine; Riffelmann, Marion; Becker, Christian; Wirsing von König, Carl Heinz

    2008-01-01

    Bead-based assay systems offer the possibility of measuring several specific antibodies in one sample simultaneously. This study evaluated a vaccine panel of a multianalyte system that measures antibodies to tetanus toxin, diphtheria toxin, and pertussis toxin (PT) from Bordetella pertussis. The antibody concentrations of human immunoglobulin G (IgG) to PT, tetanus toxin, and diphtheria toxin were measured in 123 serum pairs (total of 246 sera) from a vaccine study. The multianalyte bead assa...

  1. Determination of low tetanus or diphtheria antitoxin titers in sera by a toxin neutralization assay and a modified toxin-binding inhibition test.

    Science.gov (United States)

    Sonobe, M H; Trezena, A G; Guilhen, F B; Takano, V L; Fratelli, F; Sakauchi, D; Morais, J F; Prado, S M A; Higashi, H G

    2007-01-01

    A method for the screening of tetanus and diphtheria antibodies in serum using anatoxin (inactivated toxin) instead of toxin was developed as an alternative to the in vivo toxin neutralization assay based on the toxin-binding inhibition test (TOBI test). In this study, the serum titers (values between 1.0 and 19.5 IU) measured by a modified TOBI test (Modi-TOBI test) and toxin neutralization assays were correlated (P diphtheria antibodies were evaluated in serum samples from guinea pigs immunized with tetanus toxoid, diphtheria-tetanus or triple vaccine. For the Modi-TOBI test, after blocking the microtiter plates, standard tetanus or diphtheria antitoxin and different concentrations of guinea pig sera were incubated with the respective anatoxin. Twelve hours later, these samples were transferred to a plate previously coated with tetanus or diphtheria antitoxin to bind the remaining anatoxin. The anatoxin was then detected using a peroxidase-labeled tetanus or diphtheria antitoxin. Serum titers were calculated using a linear regression plot of the results for the corresponding standard antitoxin. For the toxin neutralization assay, L+/10/50 doses of either toxin combined with different concentrations of serum samples were inoculated into mice for anti-tetanus detection, or in guinea pigs for anti-diphtheria detection. Both assays were suitable for determining wide ranges of antitoxin levels. The linear regression plots showed high correlation coefficients for tetanus (r(2) = 0.95, P diphtheria (r(2) = 0.93, P assays. The standardized method is appropriate for evaluating titers of neutralizing antibodies, thus permitting the in vitro control of serum antitoxin levels.

  2. Potential protective immunogenicity of tetanus toxoid, diphtheria toxoid and Cross Reacting Material 197 (CRM197) when used as carrier proteins in glycoconjugates

    OpenAIRE

    Bröker, Michael

    2015-01-01

    When tetanus toxoid (TT), diphtheria toxoid (DT) or Cross Reacting Material 197 (CRM197), a non-toxic diphtheria toxin mutant protein, are used as carrier proteins in glycoconjugate vaccines, these carriers induce a protein specific antibody response as measured by in vitro assays. Here, it was evaluated whether or not glycoconjugates based on TT, DT or CRM197 can induce a protective immune response as measured by potency tests according to the European Pharmacopoeia. It could be shown, that ...

  3. Tetanus-diphtheria-acellular pertussis vaccination of adults in the USA.

    Science.gov (United States)

    Gidengil, Courtney A; Sandora, Thomas J; Lee, Grace M

    2008-07-01

    Pertussis is an important cause of morbidity and mortality, and its incidence has been increasing in adolescents and adults over the past two decades. Waning immunity in adolescents and adults may be partially responsible. Adults can suffer significant illness from pertussis and its complications, such as pneumonia, rib fractures and syncope. Moreover, adults serve as a source of disease for infants, who are more vulnerable to severe complications and even death. The economic burden of pertussis is substantial, in terms of both medical and nonmedical costs. Fortunately, the burden of pertussis disease can now be safely and effectively reduced by vaccinating adults with tetanus-diphtheria-acellular pertussis (Tdap) vaccine. Further research is needed to elucidate the role of vaccination in pregnant women and those over 65 years of age, and also to determine whether further booster doses of Tdap are needed.

  4. [Literature memories about diphtheria: Mark Twain, W.G. Sebald and Stendhal syndrome].

    Science.gov (United States)

    Ledermann, Walter

    2013-02-01

    Memories of W.G. Sebald from the diphtheria he suffered as a child, gave rise to a discussion about the origin of classic clinical descriptions and the traps memory tends. Good examples of the latter are some experiences of Stendhal, who must also be distrusted given his hypersensitivity, which gave name to a psychosomatic syndrome. Mark Twain, a more practical man, brings us back to reality with a funny story about the terror the disease caused in the late nineteenth century. This leads us to remember isolation measures and topical treatments from the period immediately preceding the antitoxin. They included manual removal of the pseudo membranes, maneuver that led Marañón to misinterpret a painting by Goya on a scene of "Lazarillo de Tormes".

  5. Development of an alternative method for testing the immunogenicity of diphtheria vaccines.

    Science.gov (United States)

    Manghi, M A; Pasetti, M F; Brero, M L; Deluchi, S; di Paola, G; Mathet, V; Eriksson, P V

    1995-04-01

    The immunogenicity of the diphtheria component of 73 commercial vaccines from five different manufacturers was tested by the toxin neutralization test (TNT) and the enzyme-linked immunosorbent assay (ELISA) developed in our laboratory. A comparison of the antibody levels measured by both assays showed a very good correlation (r = 0.95, p antibody levels as low as 5.5 x 10(-5) IU ml-1. To evaluate the possibility of accelerating the active immunization during the activity test of vaccines, an alternative schedule using one single human dose was assayed. A very good correlation was observed between the IgG antibody response obtained with this schedule and with the traditional programme. Therefore, the cost and the time required to perform the activity test may be considerably reduced when both the rapid immunization schedule and the ELISA are used.

  6. Simultaneous quantitation of diphtheria and tetanus antibodies by double antigen, time-resolved fluorescence immunoassay.

    Science.gov (United States)

    Aggerbeck, H; Nørgaard-Pedersen, B; Heron, I

    1996-04-19

    A dual, double antigen, time-resolved fluorescence immunoassay (DELFIA) for the simultaneous detection and quantitation of diphtheria (D) and tetanus (T) antibodies in sera has been developed. In the double antigen format one arm of the antibody binds to antigen coated microtitre wells and the other arm binds to labelled antigen to provide a fluorescent signal. This assay was found to be functionally specific for IgG antibodies and showed a good correlation with established toxin neutralization assays. Furthermore, the double antigen set-up was species independent, permitting the direct use of existing international references of animal origin to measure protective antibody levels in humans in international units (IU/ml). The detection limit corresponded to 0.0003 IU/ml with Eu(3+)-labelled toxoids and to 0.0035 IU/ml using Sm(3+)-labelled toxoids. The assay was fast with a high capacity making it a suitable method for serological surveillance studies.

  7. A novel fusion protein diphtheria toxin-stem cell factor (DT-SCF)-purification and characterization.

    Science.gov (United States)

    Potala, Sirisha; Verma, Rama Shanker

    2010-11-01

    Fusion toxins are an emerging class of targeted therapeutics for the treatment of cancer. Diphtheria toxin-stem cell factor (DT-SCF) is one such novel fusion toxin designed to target malignancies expressing c-kit. Since, c-kit overexpression has been reported on many types of cancers, it appeared to be a reasonably good molecule to target. In the present study, we report construction, expression, purification, and characterization of DT-SCF. DT-SCF gene coding for 1-387 amino acids of diphtheria toxin, His-Ala linker, 2-141 amino acids of SCF was cloned into expression vector with C terminal His tag. The induced DT-SCF protein was exclusively expressed in insoluble fraction. Purification of DT-SCF was achieved by inclusion body isolation and metal affinity chromatography under denaturing and reducing conditions. Purified DT-SCF was renatured partially on-column by gradually reducing denaturant concentration followed by complete refolding through rapid dilution technique. Cell viability assay provided the evidence that DT-SCF is a potent cytotoxic agent selective to cells expressing c-kit. The novelty of this study lies in employing SCF as a ligand in construction of fusion toxin to target wide range of malignancies expressing c-kit. Efficacy of DT-SCF fusion toxin was demonstrated over a range of malignancies such as chronic myeloid leukemia (K562), acute lymphoblastic leukemia (MOLT4), pancreatic carcinoma (PANC-1), and cervical carcinoma (HeLa 229). This is the first study reporting specificity and efficacy of DT-SCF against tumor cells expressing c-kit. There was significant correlation (P = 0.007) between c-kit expression on cells and their sensitivity to DT-SCF fusion toxin.

  8. Effect of diphtheria toxin T-domain on endosomal pH

    Directory of Open Access Journals (Sweden)

    A. J. Labyntsev

    2015-08-01

    Full Text Available A key step in the mode of cytotoxic action of diphtheria toxin (DT is the transfer of its catalytic domain (Cd from endosomes into the cytosol. The main activity in this process is performed by the transport domain (Td, but the molecular mechanism of its action remains unknown. We have previously shown that Td can have some influence on the endosomal transport of DT. The aim of this work was to study the effect of diphtheria toxin on the toxin compartmentalization in the intracellular transporting pathway and endosomal pH. We used recombinant fragments of DT, which differed only by the presence of Td in their structure, fused with fluorescent proteins. It was shown that the toxin fragment with Td moved slower by the pathway early-late endosomes-lysosomes, and had a slightly different pattern of colocalization with endosomal markers than DT fragment without Td. In addition, endosomes containing DT fragments with Td had a constant pH of about 6.5 from the 10th to 50th minute of observation, for the same time endosomes containing DT fragments without Td demons­trated a decrease in pH from 6.3 to 5.5. These results indicate that Td inhibits acidification of endosomal medium. One of possible explanations for this may be the effect of the ion channel formed by the T-domain on the process of the endosomal acidification. This property of Td may not only inhibit maturation of endosomes but also inhibit activation of endosomal pH-dependent proteases, and this promotes successful transport of Cd into the cell cytosol.

  9. External quality assessment for the determination of diphtheria antitoxin in human serum.

    Science.gov (United States)

    Di Giovine, Paolo; Pinto, Antonella; Olander, Rose-Marie; Sesardic, Dorothea; Stickings, Paul; Berbers, Guy; Neal, Shona; Efstratiou, Androulla; Paberza, Ruta; Dauksiene, Snieguole; Bujko, Marina; Detcheva, Antoaneta; Joks, Unna; Levent, Belkis; von Hunolstein, Christina

    2010-08-01

    Accurate determination of diphtheria toxin antibodies is of value in determining the rates of immunity within broad populations or the immune status of individuals who may be at risk of infection, by assessing responses to vaccination and immunization schedule efficacy. Here we report the results of an external quality assessment (EQA) study for diphtheria serology, performed within the dedicated surveillance network DIPNET. Twelve national laboratories from 11 European countries participated by testing a standard panel of 150 sera using their current routine method: Vero cell neutralization test (NT), double-antigen enzyme-linked immunosorbent assay (ELISA; DAE), dual double-antigen time-resolved fluorescence immunoassay (dDA-DELFIA), passive hemagglutination assay (PHA), toxin binding inhibition assay (ToBI), and in-house or commercial ELISAs. The objective of the study was not to identify the best assay, as the advantages and drawbacks of methods used were known, but to verify if laboratories using their routine method would have categorized (as negative, equivocal, or positive) a serum sample in the same way. The performance of each laboratory was determined by comparing its results on a quantitative and qualitative basis to NT results from a single reference laboratory, as this test is considered the in vitro "gold standard." The performance of laboratories using NT was generally very good, while the laboratories' performance using other in vitro methods was variable. Laboratories using ELISA and PHA performed less well than those using DAE, dDA-DELFIA, or ToBI. EQA is important for both laboratories that use in vitro nonstandardized methods and those that use commercial ELISA kits.

  10. Evaluation of toxin neutralisation in test systems for diphtheria antibody assessment.

    Science.gov (United States)

    Vandenberg, J; van der Gun, J W; Hendriksen, C F

    1999-01-01

    Over the past years, various authors have reported that the amount of toxin used in toxin neutralisation (TN) assays for diphtheria appears to influence the resulting relative antibody titre. Antibody affinity is thought to be an influencing factor. To confirm this observation and study the underlying mechanism of toxin neutralisation, a panel of sera was generated, differing in species of origin (mouse, guinea pig, and rabbit) and in affinity by using different immunisation schedules. The panel was then tested in relevant TN test systems for diphtheria antibody titration, namely the VERO cell test, the Toxin Binding Inhibition (ToBI) assay and the in vivo skin test in guinea pigs. A hyperimmune equine reference serum was used as the standard. Antibody affinity was measured in two different affinity ELISAs, the ammonium thiocyanate elution ELISA and the diethylamine inhibition ELISA. The VERO cell test clearly demonstrates the phenomenon; the higher the toxin dose used in the assay, the higher the resulting relative potency. The difference in relative antibody titre decreases as antibody affinity increases. This is especially evident when an equine hyperimmune reference serum is used as the standard. When a species homologous reference is used, the phenomenon is less distinct. The ToBI test, however, does not show the phenomenon. This discrepancy between these two test systems is being further investigated, and comparison will be made with the in vivo TN test. The findings confirm and support earlier observations. It is still unclear exactly which mechanisms are involved in the toxin neutralisation process. Antibody subclasses and class switching could play a role and will be further studied.

  11. Diphtheria toxin resistance in human lymphocytes and lymphoblasts in the in vivo somatic cell mutation test

    Energy Technology Data Exchange (ETDEWEB)

    Tomkins, D.J.; Wei, L.; Laurie, K.E.

    1985-01-01

    It has been shown that circulating peripheral blood lymphocytes can be used for the enumeration of 6-thioguanine-resistant cells that presumably arise by mutation in vivo. This somatic cell mutation test has been studied in lymphocytes from human populations exposed to known mutagens and/or carcinogens. The sensitivity of the test could be further enhanced by including other gene markers, since there is evidence for locus-specific differences in response to mutagens. Resistance to diphtheria toxin (Dip/sup r/) seemed like a potential marker to incorporate into the test because the mutation acts codominantly, can readily be selected in human diploid fibroblasts and Chinese hamster cells with no evidence for cell density or cross-feeding effects, and can be assayed for in nondividing cells by measuring protein synthesis inhibition. Blood samples were collected from seven individuals, and fresh, cryopreserved, or Epstein-Barr virus (EBV)-transformed lymphocytes were tested for continued DNA synthesis (TH-thymidine, autoradiography) or protein synthesis (TVS-methionine, scintillation counting). Both fresh and cryopreserved lymphocytes, stimulated to divide with phytohemagglutinin (PHA), continued to synthesize DNA in the presence of high doses of diphtheria toxin (DT). Similarly, both dividing (PHA-stimulated) and nondividing fresh lymphocytes carried on significant levels of protein synthesis even 68 hr after exposure to 100 flocculating units (LF)/ml DT. The results suggest that human T and B lymphocytes may not be as sensitive to DT protein synthesis inhibition as human fibroblast and Chinese hamster cells. For this reason, Dip/sup r/ may not be a suitable marker for the somatic cell mutation test.

  12. Salmonella enterica Serovar Typhi conceals the invasion-associated type three secretion system from the innate immune system by gene regulation.

    Science.gov (United States)

    Winter, Sebastian E; Winter, Maria G; Poon, Victor; Keestra, A Marijke; Sterzenbach, Torsten; Faber, Franziska; Costa, Luciana F; Cassou, Fabiane; Costa, Erica A; Alves, Geraldo E S; Paixão, Tatiane A; Santos, Renato L; Bäumler, Andreas J

    2014-07-01

    Delivery of microbial products into the mammalian cell cytosol by bacterial secretion systems is a strong stimulus for triggering pro-inflammatory host responses. Here we show that Salmonella enterica serovar Typhi (S. Typhi), the causative agent of typhoid fever, tightly regulates expression of the invasion-associated type III secretion system (T3SS-1) and thus fails to activate these innate immune signaling pathways. The S. Typhi regulatory protein TviA rapidly repressed T3SS-1 expression, thereby preventing RAC1-dependent, RIP2-dependent activation of NF-κB in epithelial cells. Heterologous expression of TviA in S. enterica serovar Typhimurium (S. Typhimurium) suppressed T3SS-1-dependent inflammatory responses generated early after infection in animal models of gastroenteritis. These results suggest that S. Typhi reduces intestinal inflammation by limiting the induction of pathogen-induced processes through regulation of virulence gene expression.

  13. Salmonella enterica Serovar Typhi conceals the invasion-associated type three secretion system from the innate immune system by gene regulation.

    Directory of Open Access Journals (Sweden)

    Sebastian E Winter

    2014-07-01

    Full Text Available Delivery of microbial products into the mammalian cell cytosol by bacterial secretion systems is a strong stimulus for triggering pro-inflammatory host responses. Here we show that Salmonella enterica serovar Typhi (S. Typhi, the causative agent of typhoid fever, tightly regulates expression of the invasion-associated type III secretion system (T3SS-1 and thus fails to activate these innate immune signaling pathways. The S. Typhi regulatory protein TviA rapidly repressed T3SS-1 expression, thereby preventing RAC1-dependent, RIP2-dependent activation of NF-κB in epithelial cells. Heterologous expression of TviA in S. enterica serovar Typhimurium (S. Typhimurium suppressed T3SS-1-dependent inflammatory responses generated early after infection in animal models of gastroenteritis. These results suggest that S. Typhi reduces intestinal inflammation by limiting the induction of pathogen-induced processes through regulation of virulence gene expression.

  14. TMFunction data: 2227 [TMFunction[Archive

    Lifescience Database Archive (English)

    Full Text Available A280C ... membrane translocation ... Diphtheria toxin Corynebacterium diphtheriae ... Lai ...ng (%) HT 1BI0 ... DTXR_CORDI (P33120) Helix T domain membrane-inserted; pore formation; deep insertion; cork

  15. Effect of a single tetanus-diphtheria vaccine dose on the immunity of elderly people in São Paulo, Brazil

    Directory of Open Access Journals (Sweden)

    Weckx L.Y.

    2006-01-01

    Full Text Available Epidemiological data regarding tetanus and diphtheria immunity in elderly people in Brazil are scarce. During the First National Immunization Campaign for the Elderly in Brazil in April 1999, 98 individuals (median age: 84 years received one tetanus-dyphtheria (Td vaccine dose (Butantan Institute, lot number 9808079/G. Inclusion criteria were elderly individuals without a history of severe immunosuppressive disease, acute infectious disease or use of immunomodulators. Blood samples were collected immediately before the vaccine and 30 days later. Serum was separated and stored at -20ºC until analysis. Tetanus and diphtheria antibodies were measured by the double-antigen ELISA test. Tetanus and diphtheria antibody concentrations lower than 0.01 IU/mL were considered to indicate the absence of protection, between 0.01 and 0.09 IU/mL were considered to indicate basic immunity, and values of 0.1 IU/mL or higher were considered to indicate full protection. Before vaccination, 18% of the individuals were susceptible to diphtheria and 94% were susceptible to tetanus. After one Td dose, 78% became fully immune to diphtheria, 13% attained basic immunity, and 9% were still susceptible to the disease. In contrast, 79% remained susceptible to tetanus, 4% had basic immunity and 17% were fully immune. Although one Td dose increases immunity to diphtheria in many elderly people who live in Brazil, a complete vaccination series appears to be necessary for the prevention of tetanus.

  16. Effect of a single tetanus-diphtheria vaccine dose on the immunity of elderly people in São Paulo, Brazil.

    Science.gov (United States)

    Weckx, L Y; Divino-Goes, K; Lihama, D M; Carraro, E; Bellei, N; Granato, C F H; Moraes-Pinto, M I de

    2006-04-01

    Epidemiological data regarding tetanus and diphtheria immunity in elderly people in Brazil are scarce. During the First National Immunization Campaign for the Elderly in Brazil in April 1999, 98 individuals (median age: 84 years) received one tetanus-dyphtheria (Td) vaccine dose (Butantan Institute, lot number 9808079/G). Inclusion criteria were elderly individuals without a history of severe immunosuppressive disease, acute infectious disease or use of immunomodulators. Blood samples were collected immediately before the vaccine and 30 days later. Serum was separated and stored at -20 degrees C until analysis. Tetanus and diphtheria antibodies were measured by the double-antigen ELISA test. Tetanus and diphtheria antibody concentrations lower than 0.01 IU/mL were considered to indicate the absence of protection, between 0.01 and 0.09 IU/mL were considered to indicate basic immunity, and values of 0.1 IU/mL or higher were considered to indicate full protection. Before vaccination, 18% of the individuals were susceptible to diphtheria and 94% were susceptible to tetanus. After one Td dose, 78% became fully immune to diphtheria, 13% attained basic immunity, and 9% were still susceptible to the disease. In contrast, 79% remained susceptible to tetanus, 4% had basic immunity and 17% were fully immune. Although one Td dose increases immunity to diphtheria in many elderly people who live in Brazil, a complete vaccination series appears to be necessary for the prevention of tetanus.

  17. Corynebacterium striatum Bacteremia Associated with a Catheter-Related Blood Stream Infection

    Directory of Open Access Journals (Sweden)

    Ueno Daisuke

    2017-01-01

    Full Text Available A 49-year-old woman visited our emergency department because of exertional dyspnea due to severe left ventricular functional failure. It progressed to disseminated intravascular coagulation and disturbance of consciousness on day 67 of admission. Gram-positive bacilli were detected from two different blood culture samples on day 67 of admission. An API-Coryne test and sequencing (1~615 bp of the 16S rRNA gene were performed, and the strain was identified as Corynebacterium striatum. The bacterium was detected from the removed central venous catheter tip too, and the patient was diagnosed with catheter-related bloodstream infection by C. striatum. However, treatment was not effective, and the patient died on day 73 of admission.

  18. Global Transcriptomic Analysis of the Response of Corynebacterium glutamicum to Vanillin

    Science.gov (United States)

    Chen, Can; Pan, Junfeng; Yang, Xiaobing; Guo, Chenghao; Ding, Wei; Si, Meiru; Zhang, Yi; Shen, Xihui; Wang, Yao

    2016-01-01

    Lignocellulosic biomass is an abundant and renewable resource for biofuels and bio-based chemicals. Vanillin is one of the major phenolic inhibitors in biomass production using lignocellulose. To assess the response of Corynebacterium glutamicum to vanillin stress, we performed a global transcriptional response analysis. The transcriptional data showed that the vanillin stress not only affected the genes involved in degradation of vanillin, but also differentially regulated several genes related to the stress response, ribosome/translation, protein secretion, and the cell envelope. Moreover, deletion of the sigH or msrA gene in C. glutamicum resulted in a decrease in cell viability under vanillin stress. These insights will promote further engineering of model industrial strains, with enhanced tolerance or degradation ability to vanillin to enable suitable production of biofuels and bio-based chemicals from lignocellulosic biomass. PMID:27760214

  19. Corynebacterium striatum Bacteremia Associated with a Catheter-Related Blood Stream Infection

    Science.gov (United States)

    Oishi, Tomohiro; Yamane, Kunikazu; Terada, Kihei

    2017-01-01

    A 49-year-old woman visited our emergency department because of exertional dyspnea due to severe left ventricular functional failure. It progressed to disseminated intravascular coagulation and disturbance of consciousness on day 67 of admission. Gram-positive bacilli were detected from two different blood culture samples on day 67 of admission. An API-Coryne test and sequencing (1~615 bp) of the 16S rRNA gene were performed, and the strain was identified as Corynebacterium striatum. The bacterium was detected from the removed central venous catheter tip too, and the patient was diagnosed with catheter-related bloodstream infection by C. striatum. However, treatment was not effective, and the patient died on day 73 of admission. PMID:28197349

  20. Characterization and crystal structure of lysine insensitive Corynebacterium glutamicum dihydrodipicolinate synthase (cDHDPS) protein.

    Science.gov (United States)

    Rice, Elena A; Bannon, Gary A; Glenn, Kevin C; Jeong, Soon Seog; Sturman, Eric J; Rydel, Timothy J

    2008-12-15

    The lysine insensitive Corynebacterium glutamicum dihydrodipicolinate synthase enzyme (cDHDPS) was recently successfully introduced into maize plants to enhance the level of lysine in the grain. To better understand lysine insensitivity of the cDHDPS, we expressed, purified, kinetically characterized the protein, and solved its X-ray crystal structure. The cDHDPS enzyme has a fold and overall structure that is highly similar to other DHDPS proteins. A noteworthy feature of the active site is the evidence that the catalytic lysine residue forms a Schiff base adduct with pyruvate. Analyses of the cDHDPS structure in the vicinity of the putative binding site for S-lysine revealed that the allosteric binding site in the Escherichia coli DHDPS protein does not exist in cDHDPS due to three non-conservative amino acids substitutions, and this is likely why cDHDPS is not feedback inhibited by lysine.

  1. Crude glycerol-based production of amino acids and putrescine by Corynebacterium glutamicum.

    Science.gov (United States)

    Meiswinkel, Tobias M; Rittmann, Doris; Lindner, Steffen N; Wendisch, Volker F

    2013-10-01

    Corynebacterium glutamicum possesses genes for glycerol kinase and glycerol-3-phosphate dehydrogenase that were shown to support slow growth with glycerol only when overexpressed from a plasmid. Pure glycerol and crude glycerol from biodiesel factories were tested for growth of recombinant strains expressing glpF, glpK and glpD from Escherichia coli. Some, but not all crude glycerol lots served as good carbon sources. Although the inhibitory compound(s) present in these crude glycerol lots remained unknown, the addition of substoichiometric glucose concentrations (below 10% by weight) enabled the utilization of some of the inhibitory crude glycerol lots. Besides growth, production of the amino acids L-glutamate, L-lysine, L-ornithine and L-arginine as well as of the diamine putrescine based on crude glycerol qualities from biodiesel factories was demonstrated.

  2. Tips and tricks for the assembly of a Corynebacterium pseudotuberculosis genome using a semiconductor sequencer

    DEFF Research Database (Denmark)

    Ramos, Rommel Thiago Jucá; Carneiro, Adriana Ribeiro; Soares, Siomar de Castro;

    2013-01-01

    New sequencing platforms have enabled rapid decoding of complete prokaryotic genomes at relatively low cost. The Ion Torrent platform is an example of these technologies, characterized by lower coverage, generating challenges for the genome assembly. One particular problem is the lack of genomes...... data obtained compared with traditional quality filter approaches. Data preprocessing prior to the de novo assembly enabled the use of known methodologies in the next-generation sequencing data assembly. Moreover, manual curation was proved to be essential for ensuring a quality assembly, which...... that enable reference-based assembly, such as the one used in the present study, Corynebacterium pseudotuberculosis biovar equi, which causes high economic losses in the US equine industry. The quality treatment strategy incorporated into the assembly pipeline enabled a 16-fold greater use of the sequencing...

  3. Global Transcriptomic Analysis of the Response of Corynebacterium glutamicum to Vanillin.

    Science.gov (United States)

    Chen, Can; Pan, Junfeng; Yang, Xiaobing; Guo, Chenghao; Ding, Wei; Si, Meiru; Zhang, Yi; Shen, Xihui; Wang, Yao

    2016-01-01

    Lignocellulosic biomass is an abundant and renewable resource for biofuels and bio-based chemicals. Vanillin is one of the major phenolic inhibitors in biomass production using lignocellulose. To assess the response of Corynebacterium glutamicum to vanillin stress, we performed a global transcriptional response analysis. The transcriptional data showed that the vanillin stress not only affected the genes involved in degradation of vanillin, but also differentially regulated several genes related to the stress response, ribosome/translation, protein secretion, and the cell envelope. Moreover, deletion of the sigH or msrA gene in C. glutamicum resulted in a decrease in cell viability under vanillin stress. These insights will promote further engineering of model industrial strains, with enhanced tolerance or degradation ability to vanillin to enable suitable production of biofuels and bio-based chemicals from lignocellulosic biomass.

  4. Glutamate Fermentation-2: Mechanism of L-Glutamate Overproduction in Corynebacterium glutamicum.

    Science.gov (United States)

    Hirasawa, Takashi; Wachi, Masaaki

    2016-12-03

    The nonpathogenic coryneform bacterium, Corynebacterium glutamicum, was isolated as an L-glutamate-overproducing microorganism by Japanese researchers and is currently utilized in various amino acid fermentation processes. L-Glutamate production by C. glutamicum is induced by limitation of biotin and addition of fatty acid ester surfactants and β-lactam antibiotics. These treatments affect the cell surface structures of C. glutamicum. After the discovery of C. glutamicum, many researchers have investigated the underlying mechanism of L-glutamate overproduction with respect to the cell surface structures of this organism. Furthermore, metabolic regulation during L-glutamate overproduction by C. glutamicum, particularly, the relationship between central carbon metabolism and L-glutamate biosynthesis, has been investigated. Recently, the role of a mechanosensitive channel protein in L-glutamate overproduction has been reported. In this chapter, mechanisms of L-glutamate overproduction by C. glutamicum have been reviewed.

  5. BIOCHEMICAL AND PHYLOGENETIC STUDIES OF CreD OF Corynebacterium glutamicum

    Directory of Open Access Journals (Sweden)

    Muhammad Tausif Chaudhry

    2015-06-01

    Full Text Available CreD characterized as Mg2+-dependent phosphohydrolase with conserved HD domain was involved in 4-cresol metabolism in Corynebacterium glutamicum. Native molecular mass of 54 kDa suggested that the biological unit is a dimer. No deoxynucleotide triphosphate triphosphohydrolase (dNTPase activity was detected for CreD. The apparent Km and Vmax values for 4-nitrophenyl phosphate were 0.35 mM and 16.23 M min-1 mg-1, respectively, while calculated values for kcat and kcat/Km were 0.4 s-1 and 1.14103 M-1 s-1, respectively. Among thiol group inhibitors, iodoacetic acid significantly inhibited phosphohydrolase activity. Sequence identity and phylogenetic analysis suggested universal existence of CreD homologues. Involvement of HD-domain hydrolase in aromatic degradation has not been reported before.

  6. In silico identification of essential proteins in Corynebacterium pseudotuberculosis based on protein

    DEFF Research Database (Denmark)

    Folador, Edson Luiz; de Carvalho, Paulo Vinícius Sanches Daltro; Silva, Wanderson Marques

    2016-01-01

    BACKGROUND: Corynebacterium pseudotuberculosis (Cp) is a gram-positive bacterium that is classified into equi and ovis serovars. The serovar ovis is the etiological agent of caseous lymphadenitis, a chronic infection affecting sheep and goats, causing economic losses due to carcass condemnation...... of the potential Cp interactome and to identify potentially essential proteins serving as putative drug targets. On average, we predict 16,669 interactions for each of the nine strains (with 15,495 interactions shared among all strains). An in silico sanity check suggests that the potential networks were...... not formed by spurious interactions but have a strong biological bias. With the inferred Cp networks we identify 181 essential proteins, among which 41 are non-host homologous. CONCLUSIONS: The list of candidate interactions of the Cp strains lay the basis for developing novel hypotheses and designing...

  7. RESULTS OF THE STRUGGLE AGAINST INFECTIOUS DISEASES IN THE LITHUANIAN SSR,

    Science.gov (United States)

    CONTROL, USSR, BRUCELLA, DISEASES, PUBLIC HEALTH, RICKETTSIA, INTESTINES, INFECTIOUS DISEASES, TREPONEMA PALLIDUM, DIAGNOSIS(MEDICINE), NEISSERIA GONORRHOEAE, CORYNEBACTERIUM DIPHTHERIAE , STREPTOCOCCUS, VACCINES.

  8. Assessing the Genotypic Differences between Strains of Corynebacterium pseudotuberculosis biovar equi through Comparative Genomics.

    Science.gov (United States)

    Baraúna, Rafael A; Ramos, Rommel T J; Veras, Adonney A O; Pinheiro, Kenny C; Benevides, Leandro J; Viana, Marcus V C; Guimarães, Luís C; Edman, Judy M; Spier, Sharon J; Azevedo, Vasco; Silva, Artur

    2017-01-01

    Seven genomes of Corynebacterium pseudotuberculosis biovar equi were sequenced on the Ion Torrent PGM platform, generating high-quality scaffolds over 2.35 Mbp. This bacterium is the causative agent of disease known as "pigeon fever" which commonly affects horses worldwide. The pangenome of biovar equi was calculated and two phylogenomic approaches were used to identify clustering patterns within Corynebacterium genus. Furthermore, other comparative analyses were performed including the prediction of genomic islands and prophages, and SNP-based phylogeny. In the phylogenomic tree, C. pseudotuberculosis was divided into two distinct clades, one formed by nitrate non-reducing species (biovar ovis) and another formed by nitrate-reducing species (biovar equi). In the latter group, the strains isolated from California were more related to each other, while the strains CIP 52.97 and 1/06-A formed the outermost clade of the biovar equi. A total of 1,355 core genes were identified, corresponding to 42.5% of the pangenome. This pangenome has one of the smallest core genomes described in the literature, suggesting a high genetic variability of biovar equi of C. pseudotuberculosis. The analysis of the similarity between the resistance islands identified a higher proximity between the strains that caused more severe infectious conditions (infection in the internal organs). Pathogenicity islands were largely conserved between strains. Several genes that modulate the pathogenicity of C. pseudotuberculosis were described including peptidases, recombination enzymes, micoside synthesis enzymes, bacteriocins with antimicrobial activity and several others. Finally, no genotypic differences were observed between the strains that caused the three different types of infection (external abscess formation, infection with abscess formation in the internal organs, and ulcerative lymphangitis). Instead, it was noted that there is a higher phenetic correlation between strains isolated at

  9. Assessing the Genotypic Differences between Strains of Corynebacterium pseudotuberculosis biovar equi through Comparative Genomics

    Science.gov (United States)

    Ramos, Rommel T. J.; Veras, Adonney A. O.; Pinheiro, Kenny C.; Benevides, Leandro J.; Edman, Judy M.; Spier, Sharon J.; Azevedo, Vasco; Silva, Artur

    2017-01-01

    Seven genomes of Corynebacterium pseudotuberculosis biovar equi were sequenced on the Ion Torrent PGM platform, generating high-quality scaffolds over 2.35 Mbp. This bacterium is the causative agent of disease known as “pigeon fever” which commonly affects horses worldwide. The pangenome of biovar equi was calculated and two phylogenomic approaches were used to identify clustering patterns within Corynebacterium genus. Furthermore, other comparative analyses were performed including the prediction of genomic islands and prophages, and SNP-based phylogeny. In the phylogenomic tree, C. pseudotuberculosis was divided into two distinct clades, one formed by nitrate non-reducing species (biovar ovis) and another formed by nitrate-reducing species (biovar equi). In the latter group, the strains isolated from California were more related to each other, while the strains CIP 52.97 and 1/06-A formed the outermost clade of the biovar equi. A total of 1,355 core genes were identified, corresponding to 42.5% of the pangenome. This pangenome has one of the smallest core genomes described in the literature, suggesting a high genetic variability of biovar equi of C. pseudotuberculosis. The analysis of the similarity between the resistance islands identified a higher proximity between the strains that caused more severe infectious conditions (infection in the internal organs). Pathogenicity islands were largely conserved between strains. Several genes that modulate the pathogenicity of C. pseudotuberculosis were described including peptidases, recombination enzymes, micoside synthesis enzymes, bacteriocins with antimicrobial activity and several others. Finally, no genotypic differences were observed between the strains that caused the three different types of infection (external abscess formation, infection with abscess formation in the internal organs, and ulcerative lymphangitis). Instead, it was noted that there is a higher phenetic correlation between strains isolated at

  10. Corynebacterium striatum infecting a malignant cutaneous lesion: the emergence of an opportunistic pathogen Corynebacterium striatum infectando lesão cutânea maligna: a emergência de um patógeno oportunista

    Directory of Open Access Journals (Sweden)

    Silvana Vargas Superti

    2009-04-01

    Full Text Available We described a case of a 27-year old male patient with skin and soft tissue infection of a neoplastic lesion caused by Corynebacterium striatum, an organism which has been rarely described as a human pathogen. Identification was confirmed by DNA sequencing. Successful treatment with penicillin was achieved. The role of the C. striatum as an emerging opportunistic pathogen is discussed.Descrevemos infecção de lesão neoplásica em paciente masculino de 27 anos, envolvendo pele e partes moles, causada por Corynebacterium striatum, um microrganismo raramente descrito como patógeno humano. A identificação foi confirmada por seqüenciamento de DNA. O paciente foi tratado com penicilina, com sucesso. O papel do C. striatum como patógeno oportunista é discutido.

  11. 聚合酶链反应检测白喉杆菌的实验研究%An experimental study on detection of corynebacterium diphtheria bypolymerase chain reaction

    Institute of Scientific and Technical Information of China (English)

    王晓春; 熊鸿燕; 张建中; 何利华; 尹焱

    2004-01-01

    目的建立检测白喉杆菌的聚合酶链反应(PCR)方法.方法用PCR扩增白喉杆菌特异的白喉外毒素B基因(toxB)片段,琼脂糖凝胶电泳检测扩增产物.结果白喉杆菌参考菌株(有毒株)均扩增出318 bp的特异性片段,而其他需鉴别诊断的常见病原菌均未扩增出此特异条带.检测灵敏度为850 f/μl基因组DNA.结论依据toxB基因建立的白喉杆菌PCR检测方法具有高度的敏感性和特异性,是诊断与鉴别诊断白喉杆菌感染的一种有效手段.

  12. Effect of Cell Wall Defect on Pathogenicity of Corynebacterium diphtheriae%细胞壁缺陷对白喉棒状杆菌致病性影响的研究

    Institute of Scientific and Technical Information of China (English)

    易旭; 王和

    2006-01-01

    检测白喉棒状杆菌稳定L型对动物的致病性,探讨细胞壁缺陷对白喉棒状杆菌致病性的影响及其可能的分子机制.采用氨苄青霉素在非高渗培养基内诱导并获得产毒性白喉棒状杆菌稳定L型纯培养物.收集白喉棒状杆菌稳定L型纯培养物及其代谢产物,将收集的高于细菌型10000倍浓度的白喉棒状杆菌稳定L型纯培养物及其代谢产物皮内注射家兔,观察局部注射部位皮肤或全身的病理改变.分别采用对流免疫电泳(CIEP)和SDS-不连续聚丙烯酰胺凝胶电泳(SDS-PAGE)检测白喉棒状杆菌稳定L型可溶性代谢产物中的白喉毒素蛋白质.结果显示,白喉棒状杆菌稳定L型不能引起动物局部或全身发生异常表现,在其可溶性代谢产物中并未检测到白喉毒素蛋白质.提示细胞壁缺陷变异可影响白喉棒状杆菌产生白喉毒素蛋白质,从而使其丧失了产生外毒素致病的作用.

  13. An Experimental Study on Detection of Corynebacterium Diphtheria by PCR Method%PCR检测临床疑似患者白喉杆菌感染的实验研究

    Institute of Scientific and Technical Information of China (English)

    乔凤娟; 任林柱; 赵红

    2007-01-01

    目的 建立临床白喉患者标本的PCR检测方法.方法 用扩增白喉杆菌外毒素B基因的PCR特异引物,检测疑似样品.结果 白喉杆菌参考菌株(有毒株)和1例疑似患者的咽拭样品均扩增出248 bp的特异性片段,其他4个临床疑似白喉患者的咽拭样品未扩增出此特异性片段.结论 PCR可用于临床快速检验白喉杆菌感染.

  14. Analysis on biological characteristics of Corynebacterium diphtheriae carried by healthy people%健康人携带的白喉棒状杆菌生物学性状分析

    Institute of Scientific and Technical Information of China (English)

    范艳霞; 邵荣标; 郑春早

    2003-01-01

    目的:探讨健康人携带的白喉棒状杆菌的生物学特性及其与标准的产毒菌株的生物学性状的差异.方法:采用鸡蛋斜面培养基,亚碲酸钾血琼脂平板和肉汤培养基观察其生长特性、测定多种生化反应性、毒力和药物敏感性.结果:健康人携带的白喉杆菌的培养特性典型均无毒力;发酵麦芽糖和发酵蔗糖的菌株较多,有较多的耐麦迪霉素、苯唑青霉素和洁霉素的菌株.结论:健康人所携带的白喉杆菌的生物学特性不同于标准的有毒力的菌株.

  15. Two injections of diphtheria-tetanus-pertussis-polio vaccine as the backbone of a simplified immunization schedule in developing countries.

    Science.gov (United States)

    Cohen, H; Nagel, J

    1984-01-01

    From studies of antibody levels induced against poliovirus types 1, 2, and 3 and against diphtheria and tetanus toxins as well as from epidemiologic studies comparing the protective effect in children of two and three doses of diphtheria-tetanus-pertussis (DTP) vaccine, respectively, it can be concluded that two injections of DTP-polio vaccine administered at least four months apart will induce immunity against the four diseases. An immunization schedule can be built up in which bacille Calmette-Guérin (BCG) vaccine is given simultaneously with the first DTP-polio injection at the age of three to eight months and vaccination against measles and--if needed--yellow fever is performed simultaneously with the second DTP-polio immunization at the age of nine to 14 months.

  16. Technical and diagnostic performance of five commercial anti-diphtheria toxoid IgG enzyme-linked immunosorbent assay kits.

    Science.gov (United States)

    Faruq, A; Dadson, L; Cox, H; Alcock, F; Parker, A R

    2010-10-01

    The technical and diagnostic performances of five commercially available enzyme-linked immunosorbent assays for the measurement of anti-diphtheria toxoid IgG antibodies were evaluated. There was good agreement between the relative sensitivities of the five assays, but the relative specificity of one of the assays differed from that of the other four assays. Three of the five assays possessed recoveries of the international reference material NIBSC 00/496 within the range of 90% to 110% at antibody levels >0.1 IU/ml. The data suggest that there are manufacture-dependent differences in relative sensitivity, specificity, and accuracy for the determination of anti-diphtheria toxoid IgG antibodies that could result in different diagnostic interpretations.

  17. Comparative quantitation for the protein content of diphtheria and tetanus toxoids by DC protein assay and Kjeldahl method.

    Science.gov (United States)

    Doshi, J B; Ravetkar, S D; Ghole, V S; Rehani, K

    2003-09-01

    DPT, a combination vaccine against diphtheria, tetanus and pertussis is available since many years and still continued in the national immunisation schedule of many countries. Although highly potent, reactions to DPT vaccine are well known, mainly attributed to the factors like Pertussis component, aluminum adjuvant and lower purity of tetanus and diphtheria toxoids. The latter most important aspect has become a matter of concern, specially for the preparation of next generation combination vaccines with more number of antigens in combination with DPT. Purity of toxoid is expressed as Lf (Limes flocculation) per mg of protein nitrogen. The Kjeldahl method (KM) of protein nitrogen estimation suggested by WHO and British Pharmacopoeia is time consuming and less specific. Need has been felt to explore an alternative method which is quick and more specific for toxoid protein determination. DC (detergent compatible) protein assay, an improved Lowry's method, has been found to be much more advantageous than Kjeldahl method.

  18. High quality draft genome sequence of Corynebacterium ulceribovis type strain IMMIB-L1395(T) (DSM 45146(T)).

    Science.gov (United States)

    Yassin, Atteyet F; Lapidus, Alla; Han, James; Reddy, T B K; Huntemann, Marcel; Pati, Amrita; Ivanova, Natalia; Markowitz, Victor; Woyke, Tanja; Klenk, Hans-Peter; Kyrpides, Nikos C

    2015-01-01

    Corynebacterium ulceribovis strain IMMIB L-1395(T) (= DSM 45146(T)) is an aerobic to facultative anaerobic, Gram-positive, non-spore-forming, non-motile rod-shaped bacterium that was isolated from the skin of the udder of a cow, in Schleswig Holstein, Germany. The cell wall of C. ulceribovis contains corynemycolic acids. The cellular fatty acids are those described for the genus Corynebacterium, but tuberculostearic acid is not present. Here we describe the features of C. ulceribovis strain IMMIB L-1395(T), together with genome sequence information and its annotation. The 2,300,451 bp long genome containing 2,104 protein-coding genes and 54 RNA-encoding genes and is part of the Genomic Encyclopedia of Type Strains, Phase I: the one thousand microbial genomes (KMG) project.

  19. A single method to stain Malassezia furfur and Corynebacterium minutissimum in scales Um método simples para corar Malassezia furfur e Corynebacterium minutissimum nas escamas

    Directory of Open Access Journals (Sweden)

    Antar Padilha-Gonçalves

    1996-08-01

    Full Text Available A single and practical method to slain Malassezia furfur and Corynebacterium minutissimum in lesions' scales is described. The scales are collected by pressing small pieces of scotch tape (about 4 cm lenght and 2 cm width onto the lesions and following withdrawl the furfuraceous scales will remain on the glue side. These pieces are then immersed for some minutes in lactophenol-cotton blue stain. Following absorption of the stain the scales are washed in current water to remove the excess of blue stain, dried with filter paper, dehydrated via passage in two bottles containing absolute alcohol and then placed in xylene in a centrifugation tube. The xylene dissolves the scotch tape glue and the scales fall free in the tube. After centrifugation and decantation the scales concentrated on the bottom of the tube are collected with a platinum-loop, placed in Canada balsam on a microscopy slide and closed with a cover slip. The preparations are then ready to be submitted to microscopic examination. Other stains may also be used instead of lactophenol-cotton blue. This method is simple, easily performed, and offers good conditions to study these fungi as well as being useful for the diagnosis of the diseases that they cause.É descrito um método simples e prático para corar Malassezia furfur e Corynebacterium minutissimum nas escamas das lesões. O material é colhido com o auxílio de fita durex que será usada na maior parte das etapas do método para ajudar a fácil execução do processo de coloração. Para colher as escamas, pequenos pedaços de fita durex com cerca de 4 cm de comprimento por 2 cm de largura são colocados e pressionados sobre as lesões, e quando retirados trazem aderidas as escamas furfuráceas na face com goma. Esses pedaços de fita durex são imersos por alguns minutos no corante lactofenol-azul cotton e logo que as escamas estiverem coradas em azul são lavadas em água corrente para remover o excesso de corante azul, secos

  20. Succinate production from CO2-grown microalgal biomass as carbon source using engineered Corynebacterium glutamicum through consolidated bioprocessing

    OpenAIRE

    Lee, Jungseok; Sim, Sang Jun; Bott, Michael; Um, Youngsoon; Oh, Min-Kyu; Woo, Han Min

    2014-01-01

    The potential for production of chemicals from microalgal biomass has been considered as an alternative route for CO2 mitigation and establishment of biorefineries. This study presents the development of consolidated bioprocessing for succinate production from microalgal biomass using engineered Corynebacterium glutamicum. Starch-degrading and succinate-producing C. glutamicum strains produced succinate (0.16 g succinate/g total carbon source) from a mixture of starch and glucose as a model m...