1887

Abstract

, the causative agent of diphtheria, has been thoroughly studied with respect to toxin production and pili formation, while knowledge on host responses to infection is limited. In this study, we studied adhesion to and invasion of epithelial cells by different isolates. When NFκ-B reporter cell lines were used to monitor the effect of 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 . Our data indicate that the response of epithelial cells to infection is determined by internalization of bacteria and that invasion of these cells is an active process; tetracycline-treated 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.

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2013-01-01
2022-08-13
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References

  1. Bennett K. L., Pearson G. D. ( 1993). Sequence conversion during postreplicative adenovirus overlap recombination. Proc Natl Acad Sci U S A 90:1397–1401 [View Article][PubMed]
    [Google Scholar]
  2. Bertuccini L., Baldassarri L., von Hunolstein C. ( 2004). Internalization of non-toxigenic Corynebacterium diphtheriae by cultured human respiratory epithelial cells. Microb Pathog 37:111–118 [View Article][PubMed]
    [Google Scholar]
  3. Bose R., Thinwa J., Chaparro P., Zhong Y., Bose S., Zhong G., Dube P. H. ( 2012). Mitogen-activated protein kinase-dependent interleukin-1α intracrine signaling is modulated by YopP during Yersinia enterocolitica infection. Infect Immun 80:289–297[PubMed] [CrossRef]
    [Google Scholar]
  4. Colombo A. V., Hirata R. Jr, de Souza C. M., Monteiro-Leal L. H., Previato J. O., Formiga L. C. D., Andrade A. F. B., Mattos-Guaraldi A. L. ( 2001). Corynebacterium diphtheriae surface proteins as adhesins to human erythrocytes. FEMS Microbiol Lett 197:235–239 [View Article][PubMed]
    [Google Scholar]
  5. Corbett D., Wang J., Schuler S., Lopez-Castejon G., Glenn S., Brough D., Andrew P. W., Cavet J. S., Roberts I. S. ( 2012). Two zinc uptake systems contribute to the full virulence of Listeria monocytogenes during growth in vitro and in vivo. Infect Immun 80:14–21[PubMed] [CrossRef]
    [Google Scholar]
  6. Corboz L., Thoma R., Braun U., Zbinden R. ( 1996). [Isolation of Corynebacterium diphtheriae subsp. belfanti from a cow with chronic active dermatitis]. Schweiz Arch Tierheilkd 138:596–599[PubMed]
    [Google Scholar]
  7. dos Santos C. S., dos Santos L. S., de Souza M. C., dos Santos Dourado F., de Souza de Oliveira Dias A. A., Sabbadini P. S., Pereira G. A., Cabral M. C., Hirata Junior R., de Mattos-Guaraldi A. L. ( 2010). Non-opsonic phagocytosis of homologous non-toxigenic and toxigenic Corynebacterium diphtheriae strains by human U-937 macrophages. Microbiol Immunol 54:1–10 [View Article][PubMed]
    [Google Scholar]
  8. Farfour E., Badell E., Zasada A., Hotzel H., Tomaso H., Guillot S., Guiso N. ( 2012). Characterization and comparison of invasive Corynebacterium diphtheriae isolates from France and Poland. J Clin Microbiol 50:173–175 [View Article][PubMed]
    [Google Scholar]
  9. Galazka A. ( 2000). The changing epidemiology of diphtheria in the vaccine era. J Infect Dis 181:Suppl. 1S2–S9 [View Article][PubMed]
    [Google Scholar]
  10. Gey G. O., Coffmann W. D., Kubicek M. T. ( 1952). Tissue culture studies of the proliferative capacity of cervical carcinoma and normal epithelium. Cancer Res 12:264–265
    [Google Scholar]
  11. Grant S. G., Jessee J., Bloom F. R., Hanahan D. ( 1990). Differential plasmid rescue from transgenic mouse DNAs into Escherichia coli methylation-restriction mutants. Proc Natl Acad Sci U S A 87:4645–4649 [View Article][PubMed]
    [Google Scholar]
  12. Hadfield T. L., McEvoy P., Polotsky Y., Tzinserling V. A., Yakovlev A. A. ( 2000). The pathology of diphtheria. J Infect Dis 181:Suppl. 1S116–S120 [View Article][PubMed]
    [Google Scholar]
  13. Hall A. J., Cassiday P. K., Bernard K. A., Bolt F., Steigerwalt A. G., Bixler D., Pawloski L. C., Whitney A. M., Iwaki M. & other authors ( 2010). Novel Corynebacterium diphtheriae in domestic cats. Emerg Infect Dis 16:688–691 [View Article][PubMed]
    [Google Scholar]
  14. Hansmeier N., Chao T. C., Kalinowski J., Pühler A., Tauch A. ( 2006). Mapping and comprehensive analysis of the extracellular and cell surface proteome of the human pathogen Corynebacterium diphtheriae . Proteomics 6:2465–2476 [View Article][PubMed]
    [Google Scholar]
  15. Hayden M. S., West A. P., Ghosh S. ( 2006). NF-κB and the immune response. Oncogene 25:6758–6780 [View Article][PubMed]
    [Google Scholar]
  16. Henricson B., Segarra M., Garvin J., Burns J., Jenkins S., Kim C., Popovic T., Golaz A., Akey B. ( 2000). Toxigenic Corynebacterium diphtheriae associated with an equine wound infection. J Vet Diagn Invest 12:253–257 [View Article][PubMed]
    [Google Scholar]
  17. Hirata R. Jr, Napoleão F., Monteiro-Leal L. H., Andrade A. F. B., Nagao P. E., Formiga L. C. D., Fonseca L. S., Mattos-Guaraldi A. L. ( 2002). Intracellular viability of toxigenic Corynebacterium diphtheriae strains in HEp-2 cells. FEMS Microbiol Lett 215:115–119 [View Article][PubMed]
    [Google Scholar]
  18. Hirata R. Jr, Souza S. M., Rocha-de-Souza C. M., Andrade A. F., Monteiro-Leal L. H., Formiga L. C., Mattos-Guaraldi A. L. ( 2004). Patterns of adherence to HEp-2 cells and actin polymerisation by toxigenic Corynebacterium diphtheriae strains. Microb Pathog 36:125–130 [View Article][PubMed]
    [Google Scholar]
  19. Hirata R. Jr, Pereira G. A., Filardy A. A., Gomes D. L., Damasco P. V., Rosa A. C., Nagao P. E., Pimenta F. P., Mattos-Guaraldi A. L. ( 2008). Potential pathogenic role of aggregative-adhering Corynebacterium diphtheriae of different clonal groups in endocarditis. Braz J Med Biol Res 41:986–991 [View Article][PubMed]
    [Google Scholar]
  20. Leggett B. A., De Zoysa A., Abbott Y. E., Leonard N., Markey B., Efstratiou A. ( 2010). Toxigenic Corynebacterium diphtheriae isolated from a wound in a horse. Vet Rec 166:656–657 [View Article][PubMed]
    [Google Scholar]
  21. Li Q., Verma I. M. ( 2002). NF-kappaB regulation in the immune system. Nat Rev Immunol 2:725–734 [View Article][PubMed]
    [Google Scholar]
  22. Mandlik A., Swierczynski A., Das A., Ton-That H. ( 2007). Corynebacterium diphtheriae employs specific minor pilins to target human pharyngeal epithelial cells. Mol Microbiol 64:111–124 [View Article][PubMed]
    [Google Scholar]
  23. Mandlik A., Swierczynski A., Das A., Ton-That H. ( 2008). Pili in Gram-positive bacteria: assembly, involvement in colonization and biofilm development. Trends Microbiol 16:33–40 [View Article][PubMed]
    [Google Scholar]
  24. Mattos-Guaraldi A. L., Duarte Formiga L. C., Pereira G. A. ( 2000). Cell surface components and adhesion in Corynebacterium diphtheriae . Microbes Infect 2:1507–1512 [View Article][PubMed]
    [Google Scholar]
  25. O’Dea E., Hoffmann A. ( 2009). NF-κB signaling. Wiley Interdiscip Rev Syst Biol Med 1:107–115 [View Article][PubMed]
    [Google Scholar]
  26. Ott L., Höller M., Gerlach R. G., Hensel M., Rheinlaender J., Schäffer T. E., Burkovski A. ( 2010a). Corynebacterium diphtheriae invasion-associated protein (DIP1281) is involved in cell surface organization, adhesion and internalization in epithelial cells. BMC Microbiol 10:2 [View Article][PubMed]
    [Google Scholar]
  27. Ott L., Höller M., Rheinlaender J., Schäffer T. E., Hensel M., Burkovski A. ( 2010b). Strain-specific differences in pili formation and the interaction of Corynebacterium diphtheriae with host cells. BMC Microbiol 10:257 [View Article][PubMed]
    [Google Scholar]
  28. Ott L., McKenzie A., Baltazar M. T., Britting S., Bischof A., Burkovski A., Hoskisson P. A. ( 2012). Evaluation of invertebrate infection models for pathogenic corynebacteria. FEMS Immunol Med Microbiol 65:413–421 [View Article][PubMed]
    [Google Scholar]
  29. Perkins N. D. ( 2007). Integrating cell-signalling pathways with NF-κB and IKK function. Nat Rev Mol Cell Biol 8:49–62 [View Article][PubMed]
    [Google Scholar]
  30. Peterson W. D. Jr, Stulberg C. S., Swanborg N. K., Robinson A. R. ( 1968). Glucose-6-phosphate dehydrogenase isoenzymes in human cell cultures determined by sucrose-agar gel and cellulose acetate zymograms. Proc Soc Exp Biol Med 128:772–776[PubMed] [CrossRef]
    [Google Scholar]
  31. Puliti M., von Hunolstein C., Marangi M., Bistoni F., Tissi L. ( 2006). Experimental model of infection with non-toxigenic strains of Corynebacterium diphtheriae and development of septic arthritis. J Med Microbiol 55:229–235 [View Article][PubMed]
    [Google Scholar]
  32. Revez J., Rossi M., Ellström P., de Haan C., Rautelin H., Hänninen M. L. ( 2011). Finnish Campylobacter jejuni strains of multilocus sequence type ST-22 complex have two lineages with different characteristics. PLoS ONE 6:e26880 [View Article][PubMed]
    [Google Scholar]
  33. Rheinlaender J., Gräbner A., Ott L., Burkovski A., Schäffer T. E. ( 2012). Contour and persistence length of Corynebacterium diphtheriae pili by atomic force microscopy. Eur Biophys J 41:561–570 [View Article][PubMed]
    [Google Scholar]
  34. Sabbadini P. S., Assis M. C., Trost E., Gomes D. L., Moreira L. O., Dos Santos C. S., Pereira G. A., Nagao P. E., Azevedo V. A. & other authors ( 2012). Corynebacterium diphtheriae 67-72p hemagglutinin, characterized as the protein DIP0733, contributes to invasion and induction of apoptosis in HEp-2 cells. Microb Pathog 52:165–176 [View Article][PubMed]
    [Google Scholar]
  35. Sambrook J., Fritsch E. F., Maniatis T. ( 1989). Molecular Cloning: a Laboratory Manual, 2nd edn. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
    [Google Scholar]
  36. Scherer W. F., Syverton J. T., Gey G. O. ( 1953). Studies on the propagation in vitro of poliomyelitis viruses. IV. Viral multiplication in a stable strain of human malignant epithelial cells (strain HeLa) derived from an epidermoid carcinoma of the cervix. J Exp Med 97:695–710 [View Article][PubMed]
    [Google Scholar]
  37. Swaminathan A., Mandlik A., Swierczynski A., Gaspar A., Das A., Ton-That H. ( 2007). Housekeeping sortase facilitates the cell wall anchoring of pilus polymers in Corynebacterium diphtheriae . Mol Microbiol 66:961–974 [View Article][PubMed]
    [Google Scholar]
  38. Tato C. M., Hunter C. A. ( 2002). Host-pathogen interactions: subversion and utilization of the NF-κB pathway during infection. Infect Immun 70:3311–3317 [View Article][PubMed]
    [Google Scholar]
  39. von Hunolstein C., Alfarone G., Scopetti F., Pataracchia M., La Valle R., Franchi F., Pacciani L., Manera A., Giammanco A. & other authors ( 2003). Molecular epidemiology and characteristics of Corynebacterium diphtheriae and Corynebacterium ulcerans strains isolated in Italy during the 1990s. J Med Microbiol 52:181–188 [View Article][PubMed]
    [Google Scholar]
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