1887

Abstract

Peptide metabolism forms an important part of the metabolic network of and to acquire these peptides the pathogen possesses a number of peptide transporters. Whilst various peptide transporters known in are well studied, very little is known about the carbon starvation () genes and , which are also predicted to be involved in peptide metabolism. We investigated the role of these genes in the metabolism and pathogenesis of , and demonstrated for the first time, to the best of our knowledge, that genes actually participate in transport of specific peptides in . Furthermore, we established that the carbon starvation gene affects the expression of flagella, leading to poor adhesion of the bacterium to host cells. In contrast to the previously reported role of in virulence of in , we showed that is required for successful colonization of in the mouse gut. Thus, genes not only contribute to the metabolism of , but also influence its virulence.

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2016-01-01
2024-04-20
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References

  1. Abouhamad W. N., Manson M., Gibson M. M., Higgins C. F. 1991; Peptide transport and chemotaxis in Escherichia coli and Salmonella typhimurium: characterization of the dipeptide permease (Dpp) and the dipeptide-binding protein. Mol Microbiol 5:1035–1047 [View Article][PubMed]
    [Google Scholar]
  2. Aderem A., Underhill D. M. 1999; Mechanisms of phagocytosis in macrophages. Annu Rev Immunol 17:593–623 [View Article][PubMed]
    [Google Scholar]
  3. Akeda Y., Galán J. E. 2004; Genetic analysis of the Salmonella enterica type III secretion-associated ATPase InvC defines discrete functional domains. J Bacteriol 186:2402–2412 [View Article][PubMed]
    [Google Scholar]
  4. Alix E., Blanc-Potard A. B. 2009; Hydrophobic peptides: novel regulators within bacterial membrane. Mol Microbiol 72:5–11 [View Article][PubMed]
    [Google Scholar]
  5. Amann E., Ochs B., Abel K. J. 1988; Tightly regulated tac promoter vectors useful for the expression of unfused and fused proteins in Escherichia coli . Gene 69:301–315 [CrossRef]
    [Google Scholar]
  6. Barthel M., Hapfelmeier S., Quintanilla-Martínez L., Kremer M., Rohde M., Hogardt M., Pfeffer K., Rüssmann H., Hardt W. D. 2003; Pretreatment of mice with streptomycin provides a Salmonella enterica serovar Typhimurium colitis model that allows analysis of both pathogen and host. Infect Immun 71:2839–2858 [View Article][PubMed]
    [Google Scholar]
  7. Bäumler A. J., Tsolis R. M., Heffron F. 1996; Contribution of fimbrial operons to attachment to and invasion of epithelial cell lines by Salmonella typhimurium . Infect Immun 64:1862–1865[PubMed]
    [Google Scholar]
  8. Bochner B. R. 2009; Global phenotypic characterization of bacteria. FEMS Microbiol Rev 33:191–205 [View Article][PubMed]
    [Google Scholar]
  9. Bonifield H. R., Hughes K. T. 2003; Flagellar phase variation in Salmonella enterica is mediated by a posttranscriptional control mechanism. J Bacteriol 185:3567–3574 [View Article][PubMed]
    [Google Scholar]
  10. Bucior I., Pielage J. F., Engel J. N. 2012; Pseudomonas aeruginosa pili and flagella mediate distinct binding and signaling events at the apical and basolateral surface of airway epithelium. PLoS Pathog 8:e1002616 [View Article][PubMed]
    [Google Scholar]
  11. Chatterjee J., Laufer B., Kessler H. 2012; Synthesis of N-methylated cyclic peptides. Nat Protoc 7:432–444 [View Article][PubMed]
    [Google Scholar]
  12. Chilcott G. S., Hughes K. T. 2000; Coupling of flagellar gene expression to flagellar assembly in Salmonella enterica serovar typhimurium and Escherichia coli . Microbiol Mol Biol Rev 64:694–708 [View Article][PubMed]
    [Google Scholar]
  13. Cundell D. R., Pearce B. J., Sandros J., Naughton A. M., Masure H. R. 1995; Peptide permeases from Streptococcus pneumoniae affect adherence to eucaryotic cells. Infect Immun 63:2493–2498[PubMed]
    [Google Scholar]
  14. Dandekar T., Astrid F., Jasmin P., Hensel M. 2012; Salmonella enterica: a surprisingly well-adapted intracellular lifestyle. Front Microbiol 3:164 [View Article][PubMed]
    [Google Scholar]
  15. Das P., Lahiri A., Chakravortty D. 2009; Novel role of the nitrite transporter NirC in Salmonella pathogenesis: SPI2-dependent suppression of inducible nitric oxide synthase in activated macrophages. Microbiology 155:2476–2489 [CrossRef]
    [Google Scholar]
  16. Datsenko K. A., Wanner B. L. 2000; One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products. Proc Natl Acad Sci U S A 97:6640–6645 [View Article][PubMed]
    [Google Scholar]
  17. Detmers F. J., Lanfermeijer F. C., Poolman B. 2001; Peptides and ATP binding cassette peptide transporters. Res Microbiol 152:245–258 [View Article][PubMed]
    [Google Scholar]
  18. Dibb-Fuller M. P., Allen-Vercoe E., Thorns C. J., Woodward M. J. 1999; Fimbriae- and flagella-mediated association with and invasion of cultured epithelial cells by Salmonella enteritidis . Microbiology 145:1023–1031 [View Article][PubMed]
    [Google Scholar]
  19. Drecktrah D., Levine-Wilkinson S., Dam T., Winfree S., Knodler L. A., Schroer T. A., Steele-Mortimer O. 2008; Dynamic behaviour of Salmonella-induced membrane tubules in epithelial cells. Traffic 9:2117–2129 [CrossRef]
    [Google Scholar]
  20. Dubey A. K., Baker C. S., Suzuki K., Jones A. D., Pandit P., Romeo T., Babitzke P. 2003; CsrA regulates translation of the Escherichia coli carbon starvation gene, cstA, by blocking ribosome access to the cstA transcript. J Bacteriol 185:4450–4460 [View Article][PubMed]
    [Google Scholar]
  21. Feasey N. A., Dougan G., Kingsley R. A., Heyderman R. S., Gordon M. A. 2012; Invasive non-typhoidal salmonella disease: an emerging and neglected tropical disease in Africa. Lancet 379:2489–2499 [View Article][PubMed]
    [Google Scholar]
  22. Finn R. D., Mistry J., Tate J., Coggill P., Heger A., Pollington J. E., Gavin O. L., Gunasekaran P., Ceric G., other authors. 2010; The Pfam protein families database. Nucleic Acids Res 38:(Database)D211–D222 [View Article][PubMed]
    [Google Scholar]
  23. Garmory H. S., Titball R. W. 2004; ATP-binding cassette transporters are targets for the development of antibacterial vaccines and therapies. Infect Immun 72:6757–6763 [View Article][PubMed]
    [Google Scholar]
  24. Gerlach R. G., Jäckel D., Stecher B., Wagner C., Lupas A., Hardt W. D., Hensel M. 2007; Salmonella Pathogenicity Island 4 encodes a giant non-fimbrial adhesin and the cognate type 1 secretion system. Cell Microbiol 9:1834–1850 [View Article][PubMed]
    [Google Scholar]
  25. Gibson M. M., Price M., Higgins C. F. 1984; Genetic characterization and molecular cloning of the tripeptide permease (tpp) genes of Salmonella typhimurium . J Bacteriol 160:122–130[PubMed]
    [Google Scholar]
  26. Girón J. A., Torres A. G., Freer E., Kaper J. B. 2002; The flagella of enteropathogenic Escherichia coli mediate adherence to epithelial cells. Mol Microbiol 44:361–379 [View Article][PubMed]
    [Google Scholar]
  27. Graziano M., St-Pierre Y., Beauchemin C., Desrosiers M., Potworowski E. F. 1998; The fate of thymocytes labeled in vivo with CFSE. Exp Cell Res 240:75–85 [View Article][PubMed]
    [Google Scholar]
  28. Haiko J., Westerlund-Wikström B. 2013; The role of the bacterial flagellum in adhesion and virulence. Biology (Basel) 2:1242–1267[PubMed]
    [Google Scholar]
  29. Hiles I. D., Powell L. M., Higgins C. F. 1987; Peptide transport in Salmonella typhimurium: molecular cloning and characterization of the oligopeptide permease genes. Mol Gen Genet 206:101–109 [View Article][PubMed]
    [Google Scholar]
  30. Inglis T. J., Robertson T., Woods D. E., Dutton N., Chang B. J. 2003; Flagellum-mediated adhesion by Burkholderia pseudomallei precedes invasion of Acanthamoeba astronyxis . Infect Immun 71:2280–2282 [View Article][PubMed]
    [Google Scholar]
  31. Jones B. D., Lee C. A., Falkow S. 1992; Invasion by Salmonella typhimurium is affected by the direction of flagellar rotation. Infect Immun 60:2475–2480[PubMed]
    [Google Scholar]
  32. Karlinsey J. E., Tanaka S., Bettenworth V., Yamaguchi S., Boos W., Aizawa S. I., Hughes K. T. 2000; Completion of the hook-basal body complex of the Salmonella typhimurium flagellum is coupled to FlgM secretion and fliC transcription. Mol Microbiol 37:1220–1231 [View Article][PubMed]
    [Google Scholar]
  33. Kim Y. M., Schmidt B. J., Kidwai A. S., Jones M. B., Deatherage Kaiser B. L., Brewer H. M., Mitchell H. D., Palsson B. O., McDermott J. E., other authors. 2013; Salmonella modulates metabolism during growth under conditions that induce expression of virulence genes. Mol Biosyst 9:1522–1534 [View Article][PubMed]
    [Google Scholar]
  34. Kishikawa J., Ibuki T., Nakamura S., Nakanishi A., Minamino T., Miyata T., Namba K., Konno H., Ueno H., other authors. 2013; Common evolutionary origin for the rotor domain of rotary ATPases and flagellar protein export apparatus. PLoS One 8:e64695 [View Article][PubMed]
    [Google Scholar]
  35. Kraxenberger T., Fried L., Behr S., Jung K. 2012; First insights into the unexplored two-component system YehU/YehT in Escherichia coli . J Bacteriol 194:4272–4284 [View Article][PubMed]
    [Google Scholar]
  36. Krogh A., Larsson B., von Heijne G., Sonnhammer E. L. 2001; Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes. J Mol Biol 305:567–580 [View Article][PubMed]
    [Google Scholar]
  37. Lee E. J., Pontes M. H., Groisman E. A. 2013; A bacterial virulence protein promotes pathogenicity by inhibiting the bacterium's own F1F0 ATP synthase. Cell 154:146–156 [View Article][PubMed]
    [Google Scholar]
  38. McNab R., Jenkinson H. F. 1998; Altered adherence properties of a Streptococcus gordonii hppA (oligopeptide permease) mutant result from transcriptional effects on cshA adhesin gene expression. Microbiology 144:127–136 [View Article][PubMed]
    [Google Scholar]
  39. Moraes P. M., Seyffert N., Silva W. M., Castro T. L., Silva R. F., Lima D. D., Hirata R. Jr, Silva A., Miyoshi A., Azevedo V. 2014; Characterization of the Opp peptide transporter of Corynebacterium pseudotuberculosis and its role in virulence and pathogenicity. BioMed Res Int 2014:489–782 [View Article][PubMed]
    [Google Scholar]
  40. Olson E. R., Dunyak D. S., Jurss L. M., Poorman R. A. 1991; Identification and characterization of dppA, an Escherichia coli gene encoding a periplasmic dipeptide transport protein. J Bacteriol 173:234–244[PubMed]
    [Google Scholar]
  41. Parra-Lopez C., Baer M. T., Groisman E. A. 1993; Molecular genetic analysis of a locus required for resistance to antimicrobial peptides in Salmonella typhimurium . EMBO J 12:4053–4062[PubMed]
    [Google Scholar]
  42. Peterson M. D., Mooseker M. S. 1992; Characterization of the enterocyte-like brush border cytoskeleton of the C2BBe clones of the human intestinal cell line, Caco-2. J Cell Sci 102:581–600[PubMed]
    [Google Scholar]
  43. Podbielski A., Leonard B. A. 1998; The group A streptococcal dipeptide permease (Dpp) is involved in the uptake of essential amino acids and affects the expression of cysteine protease. Mol Microbiol 28:1323–1334 [View Article][PubMed]
    [Google Scholar]
  44. Pontes M. H., Lee E. J., Choi J., Groisman E. A. 2015; Salmonella promotes virulence by repressing cellulose production. Proc Natl Acad Sci U S A 112:5183–5188 [View Article][PubMed]
    [Google Scholar]
  45. Rabsch W., Andrews H. L., Kingsley R. A., Prager R., Tschäpe H., Adams L. G., Bäumler A. J. 2002; Salmonella enterica serotype Typhimurium and its host-adapted variants. Infect Immun 70:2249–2255 [View Article][PubMed]
    [Google Scholar]
  46. Raffatellu M., Wilson R. P., Chessa D., Andrews-Polymenis H., Tran Q. T., Lawhon S., Khare S., Adams L. G., Bäumler A. J. 2005; SipA, SopA, SopB, SopD, and SopE2 contribute to Salmonella enterica serotype typhimurium invasion of epithelial cells. Infect Immun 73:146–154 [View Article][PubMed]
    [Google Scholar]
  47. Samen U., Gottschalk B., Eikmanns B. J., Reinscheid D. J. 2004; Relevance of peptide uptake systems to the physiology and virulence of Streptococcus agalactiae . J Bacteriol 186:1398–1408 [View Article][PubMed]
    [Google Scholar]
  48. Schmitt C. K., Ikeda J. S., Darnell S. C., Watson P. R., Bispham J., Wallis T. S., Weinstein D. L., Metcalf E. S., O'Brien A. D. 2001; Absence of all components of the flagellar export and synthesis machinery differentially alters virulence of Salmonella enterica serovar Typhimurium in models of typhoid fever, survival in macrophages, tissue culture invasiveness, and calf enterocolitis. Infect Immun 69:5619–5625 [View Article][PubMed]
    [Google Scholar]
  49. Schultz J. E., Matin A. 1991; Molecular and functional characterization of a carbon starvation gene of Escherichia coli . J Mol Biol 218:129–140 [View Article][PubMed]
    [Google Scholar]
  50. Schultz J. E., Latter G. I., Matin A. 1988; Differential regulation by cyclic AMP of starvation protein synthesis in Escherichia coli . J Bacteriol 170:3903–3909[PubMed]
    [Google Scholar]
  51. Slamti L., Lereclus D. 2002; A cell-cell signaling peptide activates the PlcR virulence regulon in bacteria of the Bacillus cereus group. EMBO J 21:4550–4559 [View Article][PubMed]
    [Google Scholar]
  52. Spector M. P. 1998; The starvation-stress response (SSR) of Salmonella . Adv Microb Physiol 40:233–279 [View Article][PubMed]
    [Google Scholar]
  53. Stecher B., Hapfelmeier S., Müller C., Kremer M., Stallmach T., Hardt W. D. 2004; Flagella and chemotaxis are required for efficient induction of Salmonella enterica serovar Typhimurium colitis in streptomycin-pretreated mice. Infect Immun 72:4138–4150 [View Article][PubMed]
    [Google Scholar]
  54. Steeb B., Claudi B., Burton N. A., Tienz P., Schmidt A., Farhan H., Mazé A., Bumann D. 2013; Parallel exploitation of diverse host nutrients enhances Salmonella virulence. PLoS Pathog 9:e1003301 [View Article][PubMed]
    [Google Scholar]
  55. Tasteyre A., Barc M. C., Collignon A., Boureau H., Karjalainen T. 2001; Role of FliC and FliD flagellar proteins of Clostridium difficile in adherence and gut colonization. Infect Immun 69:7937–7940 [View Article][PubMed]
    [Google Scholar]
  56. Tenor J. L., McCormick B. A., Ausubel F. M., Aballay A. 2004; Caenorhabditis elegans-based screen identifies Salmonella virulence factors required for conserved host-pathogen interactions. Curr Biol 14:1018–1024 [View Article][PubMed]
    [Google Scholar]
  57. Thompson J. A., Liu M., Helaine S., Holden D. W. 2011; Contribution of the PhoP/Q regulon to survival and replication of Salmonella enterica serovar Typhimurium in macrophages. Microbiology 157:2084–2093 [View Article][PubMed]
    [Google Scholar]
  58. Uzzau S., Brown D. J., Wallis T., Rubino S., Leori G., Bernard S., Casadesús J., Platt D. J., Olsen J. E. 2000; Host adapted serotypes of Salmonella enterica . Epidemiol Infect 125:229–255 [View Article][PubMed]
    [Google Scholar]
  59. Vorwerk H., Mohr J., Huber C., Wensel O., Schmidt-Hohagen K., Gripp E., Josenhans C., Schomburg D., Eisenreich W., Hofreuter D. 2014; Utilization of host-derived cysteine-containing peptides overcomes the restricted sulphur metabolism of Campylobacter jejuni . Mol Microbiol 93:1224–1245[PubMed]
    [Google Scholar]
  60. Weening E. H., Barker J. D., Laarakker M. C., Humphries A. D., Tsolis R. M., Bäumler A. J. 2005; The Salmonella enterica serotype Typhimurium lpf, bcf, stb, stc, std, and sth fimbrial operons are required for intestinal persistence in mice. Infect Immun 73:3358–3366 [View Article][PubMed]
    [Google Scholar]
  61. Wong V. K., Pickard D. J., Barquist L., Sivaraman K., Page A. J., Hart P. J., Arends M. J., Holt K. E., Kane L., other authors. 2013; Characterization of the yehUT two-component regulatory system of Salmonella enterica Serovar Typhi and Typhimurium. PLoS One 8:e84567 [View Article][PubMed]
    [Google Scholar]
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