1887

Abstract

The type III secretion system 2 (ETT2) is found in most strains, including pathogenic and commensal strains. Although many ETT2 gene clusters carry multiple genetic mutations or deletions, ETT2 is known to be involved in bacterial virulence. In enterohaemorrhagic (EHEC), ETT2 affects adhesion through the regulator EtrA, which regulates transcription and secretion of the type III secretion system (T3SS) encoded by the locus of enterocyte effacement (LEE). To date, no studies have been conducted on the role of EtrA in the virulence of avian pathogenic (APEC), which harbours only ETT2. Thus, we constructed mutant and complemented strains of APEC and evaluated their phenotypes and pathogenicities. We found that the gene deletion significantly reduced bacterial survival in macrophages, and proliferation and virulence in ducks. In addition, the gene deletion reduced expression of the APEC fimbriae genes. Upregulation of genes encoding the pro-inflammatory cytokines interleukin (IL)-1β and IL-8 was also observed in HD-11 macrophages infected with the gene mutant strain compared to the wild-type strain. Furthermore, the altered capacities of the mutant strain were restored by genetic complementation. Our observations demonstrate that the ETT2 regulator EtrA contributes to the virulence of APEC.

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2017-10-01
2024-12-03
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References

  1. Coburn B, Sekirov I, Finlay BB. Type III secretion systems and disease. Clin Microbiol Rev 2007; 20:535–549 [View Article][PubMed]
    [Google Scholar]
  2. Mota LJ, Cornelis GR. The bacterial injection kit: type III secretion systems. Ann Med 2005; 37:234–249 [View Article][PubMed]
    [Google Scholar]
  3. Cornelis GR, van Gijsegem F. Assembly and function of type III secretory systems. Annu Rev Microbiol 2000; 54:735–774 [View Article][PubMed]
    [Google Scholar]
  4. Galán JE, Lara-Tejero M, Marlovits TC, Wagner S. Bacterial type III secretion systems: specialized nanomachines for protein delivery into target cells. Annu Rev Microbiol 2014; 68:415–438 [View Article][PubMed]
    [Google Scholar]
  5. Moest TP, Méresse S. Salmonella T3SSs: successful mission of the secret(ion) agents. Curr Opin Microbiol 2013; 16:38–44 [View Article][PubMed]
    [Google Scholar]
  6. Jones MA, Hulme SD, Barrow PA, Wigley P. The Salmonella pathogenicity island 1 and Salmonella pathogenicity island 2 type III secretion systems play a major role in pathogenesis of systemic disease and gastrointestinal tract colonization of Salmonella enterica serovar Typhimurium in the chicken. Avian Pathol 2007; 36:199–203 [View Article][PubMed]
    [Google Scholar]
  7. Franzin FM, Sircili MP. Locus of enterocyte effacement: a pathogenicity island involved in the virulence of enteropathogenic and enterohemorragic Escherichia coli subjected to a complex network of gene regulation. Biomed Res Int 2015; 2015:1–10 [View Article][PubMed]
    [Google Scholar]
  8. Makino S, Tobe T, Asakura H, Watarai M, Ikeda T et al. Distribution of the secondary type III secretion system locus found in enterohemorrhagic Escherichia coli O157:H7 isolates among Shiga toxin-producing E. coli strains. J Clin Microbiol 2003; 41:2341–2347 [View Article][PubMed]
    [Google Scholar]
  9. Wang S, Liu X, Xu X, Zhao Y, Yang D et al. Escherichia coli type III secretion system 2 (ETT2) is widely distributed in avian pathogenic Escherichia coli isolates from Eastern China. Epidemiol Infect 2016; 144:2824–2830 [View Article][PubMed]
    [Google Scholar]
  10. Ren CP, Chaudhuri RR, Fivian A, Bailey CM, Antonio M et al. The ETT2 gene cluster, encoding a second type III secretion system from Escherichia coli, is present in the majority of strains but has undergone widespread mutational attrition. J Bacteriol 2004; 186:3547–3560 [View Article][PubMed]
    [Google Scholar]
  11. Perna NT, Plunkett G, Burland V, Mau B, Glasner JD et al. Genome sequence of enterohaemorrhagic Escherichia coli O157:H7. Nature 2001; 409:529–533 [View Article][PubMed]
    [Google Scholar]
  12. Prager R, Bauerfeind R, Tietze E, Behrend J, Fruth A et al. Prevalence and deletion types of the pathogenicity Island ETT2 among Escherichia coli strains from oedema disease and colibacillosis in pigs. Vet Microbiol 2004; 99:287–294 [View Article][PubMed]
    [Google Scholar]
  13. Cheng D, Zhu S, Su Z, Zuo W, Lu H. Prevalence and isoforms of the pathogenicity island ETT2 among Escherichia coli isolates from colibacillosis in pigs and mastitis in cows. Curr Microbiol 2012; 64:43–49 [View Article][PubMed]
    [Google Scholar]
  14. Hayashi T, Makino K, Ohnishi M, Kurokawa K, Ishii K et al. Complete genome sequence of enterohemorrhagic Escherichia coli O157:H7 and genomic comparison with a laboratory strain K-12. DNA Res 2001; 8:11–22 [View Article][PubMed]
    [Google Scholar]
  15. Zhou M, Guo Z, Duan Q, Hardwidge PR, Zhu G. Escherichia coli type III secretion system 2: a new kind of T3SS?. Vet Res 2014; 45:32 [View Article][PubMed]
    [Google Scholar]
  16. Zhang L, Chaudhuri RR, Constantinidou C, Hobman JL, Patel MD et al. Regulators encoded in the Escherichia coli type III secretion system 2 gene cluster influence expression of genes within the locus for enterocyte effacement in enterohemorrhagic E. coli O157:H7. Infect Immun 2004; 72:7282–7293 [View Article][PubMed]
    [Google Scholar]
  17. Luzader DH, Willsey GG, Wargo MJ, Kendall MM. The type three secretion system 2-encoded regulator EtrB modulates enterohemorrhagic Escherichia coli virulence gene expression. Infect Immun 2016; 84:2555–2565 [View Article][PubMed]
    [Google Scholar]
  18. Hüttener M, Dietrich M, Paytubi S, Juárez A. HilA-like regulators in Escherichia coli pathotypes: the YgeH protein from the enteroaggregative strain 042. BMC Microbiol 2014; 14:268 [View Article][PubMed]
    [Google Scholar]
  19. Ideses D, Gophna U, Paitan Y, Chaudhuri RR, Pallen MJ et al. A degenerate type III secretion system from septicemic Escherichia coli contributes to pathogenesis. J Bacteriol 2005; 187:8164–8171 [View Article][PubMed]
    [Google Scholar]
  20. Yao Y, Xie Y, Perace D, Zhong Y, Lu J et al. The type III secretion system is involved in the invasion and intracellular survival of Escherichia coli K1 in human brain microvascular endothelial cells. FEMS Microbiol Lett 2009; 300:18–24 [View Article][PubMed]
    [Google Scholar]
  21. Wang S, Liu X, Xu X, Yang D, Wang D et al. Escherichia coli type III secretion system 2 ATPase EivC is involved in the motility and virulence of avian pathogenic Escherichia coli. Front Microbiol 2016; 7:1387 [View Article][PubMed]
    [Google Scholar]
  22. Rodriguez-Siek KE, Giddings CW, Doetkott C, Johnson TJ, Nolan LK. Characterizing the APEC pathotype. Vet Res 2005; 36:241–256 [View Article][PubMed]
    [Google Scholar]
  23. Ewers C, Li G, Wilking H, Kiessling S, Alt K et al. Avian pathogenic, uropathogenic, and newborn meningitis-causing Escherichia coli: how closely related are they?. Int J Med Microbiol 2007; 297:163–176 [View Article][PubMed]
    [Google Scholar]
  24. Tivendale KA, Logue CM, Kariyawasam S, Jordan D, Hussein A et al. Avian-pathogenic Escherichia coli strains are similar to neonatal meningitis E. coli strains and are able to cause meningitis in the rat model of human disease. Infect Immun 2010; 78:3412–3419 [View Article][PubMed]
    [Google Scholar]
  25. Krishnan S, Chang AC, Hodges J, Couraud PO, Romero IA et al. Serotype O18 avian pathogenic and neonatal meningitis Escherichia coli strains employ similar pathogenic strategies for the onset of meningitis. Virulence 2015; 6:777–786 [View Article][PubMed]
    [Google Scholar]
  26. Datsenko KA, Wanner BL. One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products. Proc Natl Acad Sci USA 2000; 97:6640–6645 [View Article][PubMed]
    [Google Scholar]
  27. Wang S, Dai J, Meng Q, Han X, Han Y et al. DotU expression is highly induced during in vivo infection and responsible for virulence and Hcp1 secretion in avian pathogenic Escherichia coli. Front Microbiol 2014; 5:588 [View Article][PubMed]
    [Google Scholar]
  28. Wang S, Niu C, Shi Z, Xia Y, Yaqoob M et al. Effects of ibeA deletion on virulence and biofilm formation of avian pathogenic Escherichia coli. Infect Immun 2011; 79:279–287 [View Article][PubMed]
    [Google Scholar]
  29. Ishihama A. Prokaryotic genome regulation: multifactor promoters, multitarget regulators and hierarchic networks. FEMS Microbiol Rev 2010; 34:628–645 [View Article][PubMed]
    [Google Scholar]
  30. Miyazaki J, Ba-Thein W, Kumao T, Akaza H, Hayashi H. Identification of a type III secretion system in uropathogenic Escherichia coli. FEMS Microbiol Lett 2002; 212:221–228 [View Article][PubMed]
    [Google Scholar]
  31. Van Kessel JC, Ulrich LE, Zhulin IB, Bassler BL. Analysis of activator and repressor functions reveals the requirements for transcriptional control by LuxR, the master regulator of quorum sensing in Vibrio harveyi. MBio 2013; 4:e00378-13 [View Article][PubMed]
    [Google Scholar]
  32. Croxen MA, Finlay BB. Molecular mechanisms of Escherichia coli pathogenicity. Nat Rev Microbiol 2010; 8:26–38 [View Article][PubMed]
    [Google Scholar]
  33. Sukumaran SK, Shimada H, Prasadarao NV. Entry and intracellular replication of Escherichia coli K1 in macrophages require expression of outer membrane protein A. Infect Immun 2003; 71:5951–5961 [View Article][PubMed]
    [Google Scholar]
  34. Le Bouguénec C. Adhesins and invasins of pathogenic Escherichia coli. Int J Med Microbiol 2005; 295:471–478 [View Article][PubMed]
    [Google Scholar]
  35. Rendón MA, Saldaña Z, Erdem AL, Monteiro-Neto V, Vázquez A et al. Commensal and pathogenic Escherichia coli use a common pilus adherence factor for epithelial cell colonization. Proc Natl Acad Sci USA 2007; 104:10637–10642 [View Article][PubMed]
    [Google Scholar]
  36. Lüthje P, Brauner A. Virulence factors of uropathogenic E. coli and their interaction with the host. Adv Microb Physiol 2014; 65:337–372 [View Article][PubMed]
    [Google Scholar]
  37. Li G, Tivendale KA, Liu P, Feng Y, Wannemuehler Y et al. Transcriptome analysis of avian pathogenic Escherichia coli O1 in chicken serum reveals adaptive responses to systemic infection. Infect Immun 2011; 79:1951–1960 [View Article][PubMed]
    [Google Scholar]
  38. Johannessen M, Askarian F, Sangvik M, Sollid JE. Bacterial interference with canonical NFκB signalling. Microbiology 2013; 159:2001–2013 [View Article][PubMed]
    [Google Scholar]
  39. Raymond B, Young JC, Pallett M, Endres RG, Clements A et al. Subversion of trafficking, apoptosis, and innate immunity by type III secretion system effectors. Trends Microbiol 2013; 21:430–441 [View Article][PubMed]
    [Google Scholar]
  40. Sémiramoth N, Gleizes A, Turbica I, Sandré C, Gorges R et al. Escherichia coli type 1 pili trigger late IL-8 production by neutrophil-like differentiated PLB-985 cells through a Src family kinase- and MAPK-dependent mechanism. J Leukoc Biol 2009; 85:310–321 [View Article][PubMed]
    [Google Scholar]
  41. Farfan MJ, Cantero L, Vergara A, Vidal R, Torres AG. The long polar fimbriae of STEC O157:H7 induce expression of pro-inflammatory markers by intestinal epithelial cells. Vet Immunol Immunopathol 2013; 152:126–131 [View Article][PubMed]
    [Google Scholar]
  42. Kline T, Felise HB, Sanowar S, Miller SI. The type III secretion system as a source of novel antibacterial drug targets. Curr Drug Targets 2012; 13:338–351 [View Article][PubMed]
    [Google Scholar]
  43. Marshall NC, Finlay BB. Targeting the type III secretion system to treat bacterial infections. Expert Opin Ther Targets 2014; 18:137–152 [View Article][PubMed]
    [Google Scholar]
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