1887

Abstract

Pathogenic micro-organisms have evolved many strategies to counteract the antimicrobial peptides (AMPs) that they encounter upon entry into host systems. These strategies play vital roles in the virulence of pathogenic micro-organisms. The serovar Typhimurium genome has a gene cluster consisting of and genes, which encode a putative ATP-binding cassette (ABC) transporter. Our study shows that these genes constitute an operon. We deleted the gene, which encodes the ATPase component of the putative ABC transporter. The Δ strain showed increased sensitivity to protamine, melittin, polymyxin B, human defensin (HBD)-1 and HBD-2, and was compromised in its capacity to proliferate inside activated macrophages and epithelial cells. Inside Intestine 407 cells, was found to co-localize with human defensins HD-5 and HBD-1; this suggests that the ability to counteract AMPs in the intracellular milieu is important for . In a murine typhoid model, the Δ strain displayed decreased virulence when infected intragastrically. These findings suggest that the putative transporter encoded by the operon is involved in counteracting AMPs, and that it contributes to the virulence of .

Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.2007/011114-0
2008-02-01
2020-08-12
Loading full text...

Full text loading...

/deliver/fulltext/micro/154/2/666.html?itemId=/content/journal/micro/10.1099/mic.0.2007/011114-0&mimeType=html&fmt=ahah

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 Microbiol5:1035–1047
    [Google Scholar]
  2. Agerberth B., Charo J., Werr J., Olsson B., Idali F., Lindbom L., Kiessling R., Jörnvall H., Wigzell H., Gudmundsson G. H.. 2000; The human antimicrobial and chemotactic peptides LL-37 and α -defensins are expressed by specific lymphocyte and monocyte populations. Blood96:3086–3093
    [Google Scholar]
  3. Antal M., Bordeau V., Douchin V., Felden B.. 2005; A small bacterial RNA regulates a putative ABC transporter. J Biol Chem280:7901–7908
    [Google Scholar]
  4. Ayabe T., Satchell D. P., Wilson C. L., Parks W. C., Selsted M. E., Ouellette A. J.. 2000; Secretion of microbicidal α -defensins by intestinal Paneth cells in response to bacteria. Nat Immunol1:113–118
    [Google Scholar]
  5. Beuzon C. R., Holden D. W.. 2001; Use of mixed infections with Salmonella strains to study virulence genes and their interactions in vivo . Microbes Infect3:1345–1352
    [Google Scholar]
  6. Brodsky I. E., Ernst R. K., Miller S. I., Falkow S.. 2002; mig-14 is a Salmonella gene that plays a role in bacterial resistance to antimicrobial peptides. J Bacteriol184:3203–3213
    [Google Scholar]
  7. Brodsky I. E., Ghori N., Falkow S., Monack D.. 2005; Mig-14 is an inner membrane-associated protein that promotes Salmonella typhimurium resistance to CRAMP, survival within activated macrophages and persistent infection. Mol Microbiol55:954–972
    [Google Scholar]
  8. Chakravortty D., Rohde M., Jager L., Deiwick J., Hensel M.. 2005; Formation of a novel surface structure encoded by Salmonella Pathogenicity Island 2. EMBO J24:2043–2052
    [Google Scholar]
  9. 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 A97:6640–6645
    [Google Scholar]
  10. Ding A. H., Nathan C. F., Stuehr D. J.. 1988; Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages. Comparison of activating cytokines and evidence for independent production. J Immunol141:2407–2412
    [Google Scholar]
  11. Eriksson S., Lucchini S., Thompson A., Rhen M., Hinton J. C.. 2003; Unravelling the biology of macrophage infection by gene expression profiling of intracellular Salmonella enterica . Mol Microbiol47:103–118
    [Google Scholar]
  12. Fahlgren A., Hammarstrom S., Danielsson A., Hammarstrom M. L.. 2004; β -Defensin-3 and −4 in intestinal epithelial cells display increased mRNA expression in ulcerative colitis. Clin Exp Immunol137:379–385
    [Google Scholar]
  13. Faucher S. P., Porwollik S., Dozois C. M., McClelland M., Daigle F.. 2006; Transcriptome of Salmonella enterica serovar Typhi within macrophages revealed through the selective capture of transcribed sequences. Proc Natl Acad Sci U S A103:1906–1911
    [Google Scholar]
  14. Fields P. I., Groisman E. A., Heffron F.. 1989; A Salmonella locus that controls resistance to microbicidal proteins from phagocytic cells. Science243:1059–1062
    [Google Scholar]
  15. Ganz T., Selsted M. E., Lehrer R. I.. 1990; Defensins. Eur J Haematol44:1–8
    [Google Scholar]
  16. Ghosh D., Porter E., Shen B., Lee S. K., Wilk D., Drazba J., Yadav S. P., Crabb J. W., Ganz T., Bevins C. L.. 2002; Paneth cell trypsin is the processing enzyme for human defensin-5. Nat Immunol3:583–590
    [Google Scholar]
  17. Glynn M. K., Bopp C., Dewitt W., Dabney P., Mokhtar M., Angulo F. J.. 1998; Emergence of multidrug-resistant Salmonella enterica serotype Typhimurium DT104 infections in the United States. N Engl J Med338:1333–1338
    [Google Scholar]
  18. Groisman E. A., Parra-Lopez C., Salcedo M., Lipps C. J., Heffron F.. 1992; Resistance to host antimicrobial peptides is necessary for Salmonella virulence. Proc Natl Acad Sci U S A89:11939–11943
    [Google Scholar]
  19. Guina T., Yi E. C., Wang H., Hackett M., Miller S. I.. 2000; A PhoP-regulated outer membrane protease of Salmonella enterica serovar Typhimurium promotes resistance to α -helical antimicrobial peptides. J Bacteriol182:4077–4086
    [Google Scholar]
  20. Gunn J. S., Ryan S. S., Van Velkinburgh J. C., Ernst R. K., Miller S. I.. 2000; Genetic and functional analysis of a PmrA–PmrB-regulated locus necessary for lipopolysaccharide modification, antimicrobial peptide resistance, and oral virulence of Salmonella enterica serovar Typhimurium. Infect Immun68:6139–6146
    [Google Scholar]
  21. Guo L., Lim K. B., Poduje C. M., Daniel M., Gunn J. S., Hackett M., Miller S. I.. 1998; Lipid A acylation and bacterial resistance against vertebrate antimicrobial peptides. Cell95:189–198
    [Google Scholar]
  22. Hancock R. E., Chapple D. S.. 1999; Peptide antibiotics. Antimicrob Agents Chemother43:1317–1323
    [Google Scholar]
  23. Harms C., Domoto Y., Celik C., Rahe E., Stumpe S., Schmid R., Nakamura T., Bakker E. P.. 2001; Identification of the ABC protein SapD as the subunit that confers ATP dependence to the K+-uptake systems Trk(H) and Trk(G) from Escherichia coli K-12. Microbiology147:2991–3003
    [Google Scholar]
  24. Hiemstra P. S., Eisenhauer P. B., Harwig S. S., van den Barselaar M. T., van Furth R., Lehrer R. I.. 1993; Antimicrobial proteins of murine macrophages. Infect Immun61:3038–3046
    [Google Scholar]
  25. 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 Genet206:101–109
    [Google Scholar]
  26. Houde M., Bertholet S., Gagnon E., Brunet S., Goyette G., Laplante A., Princiotta M. F., Thibault P., Sacks D., Desjardins M.. 2003; Phagosomes are competent organelles for antigen cross-presentation. Nature425:402–406
    [Google Scholar]
  27. Ishibashi Y., Arai T.. 1990; Effect of γ -interferon on phagosome-lysosome fusion in Salmonella typhimurium -infected murine macrophages. FEMS Microbiol Immunol2:75–82
    [Google Scholar]
  28. Knodler L. A., Bestor A., Ma C., Hansen-Wester I., Hensel M., Vallance B. A., Steele-Mortimer O.. 2005; Cloning vectors and fluorescent proteins can significantly inhibit Salmonella enterica virulence in both epithelial cells and macrophages: implications for bacterial pathogenesis studies. Infect Immun73:7027–7031
    [Google Scholar]
  29. Lehrer R. I.. 2007; Multispecific myeloid defensins. Curr Opin Hematol14:16–21
    [Google Scholar]
  30. Lehrer R. I., Ganz T.. 1999; Antimicrobial peptides in mammalian and insect host defense. Curr Opin Immunol11:23–27
    [Google Scholar]
  31. Lehrer R. I., Barton A., Daher K. A., Harwig S. S., Ganz T., Selsted M. E.. 1989; Interaction of human defensins with Escherichia coli . Mechanism of bactericidal activity. J Clin Invest84:553–561
    [Google Scholar]
  32. Lopez-Solanilla E., Garcia-Olmedo F., Rodriguez-Palenzuela P.. 1998; Inactivation of the sapA to sapF locus of Erwinia chrysanthemi reveals common features in plant and animal bacterial pathogenesis. Plant Cell10:917–924
    [Google Scholar]
  33. Mason K. M., Munson R. S. Jr, Bakaletz L. O.. 2005; A mutation in the sap operon attenuates survival of nontypeable Haemophilus influenzae in a chinchilla model of otitis media. Infect Immun73:599–608
    [Google Scholar]
  34. Mei J. M., Nourbakhsh F., Ford C. W., Holden D. W.. 1997; Identification of Staphylococcus aureus virulence genes in a murine model of bacteraemia using signature-tagged mutagenesis. Mol Microbiol26:399–407
    [Google Scholar]
  35. Mineshiba J., Myokai F., Mineshiba F., Matsuura K., Nishimura F., Takashiba S.. 2005; Transcriptional regulation of β -defensin-2 by lipopolysaccharide in cultured human cervical carcinoma (HeLa) cells. FEMS Immunol Med Microbiol45:37–44
    [Google Scholar]
  36. Molbak K., Baggesen D. L., Aarestrup F. M., Ebbesen J. M., Engberg J., Frydendahl K., Gerner-Smidt P., Petersen A. M., Wegener H. C.. 1999; An outbreak of multidrug-resistant, quinolone-resistant Salmonella enterica serotype Typhimurium DT104. N Engl J Med341:1420–1425
    [Google Scholar]
  37. Ogushi K., Wada A., Niidome T., Mori N., Oishi K., Nagatake T., Takahashi A., Asakura H., Makino S.. other authors 2001; Salmonella enteritidis FliC (flagella filament protein) induces human β -defensin-2 mRNA production by Caco-2 cells. J Biol Chem276:30521–30526
    [Google Scholar]
  38. Ogushi K., Wada A., Niidome T., Okuda T., Llanes R., Nakayama M., Nishi Y., Kurazono H., Smith K. D.. other authors 2004; Gangliosides act as co-receptors for Salmonella enteritidis FliC and promote FliC induction of human β -defensin-2 expression in Caco-2 cells. J Biol Chem279:12213–12219
    [Google Scholar]
  39. O'Neil D. A., Porter E. M., Elewaut D., Anderson G. M., Eckmann L., Ganz T., Kagnoff M. F.. 1999; Expression and regulation of the human β -defensins hBD-1 and hBD-2 in intestinal epithelium. J Immunol163:6718–6724
    [Google Scholar]
  40. Ouellette A. J., Hsieh M. M., Nosek M. T., Cano-Gauci D. F., Huttner K. M., Buick R. N., Selsted M. E.. 1994; Mouse Paneth cell defensins: primary structures and antibacterial activities of numerous cryptdin isoforms. Infect Immun62:5040–5047
    [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 J12:4053–4062
    [Google Scholar]
  42. Parra-Lopez C., Lin R., Aspedon A., Groisman E. A.. 1994; A Salmonella protein that is required for resistance to antimicrobial peptides and transport of potassium. EMBO J13:3964–3972
    [Google Scholar]
  43. Peschel A.. 2002; How do bacteria resist human antimicrobial peptides?. Trends Microbiol10:179–186
    [Google Scholar]
  44. Petronilli V., Ames G. F.. 1991; Binding protein-independent histidine permease mutants. Uncoupling of ATP hydrolysis from transmembrane signaling. J Biol Chem266:16293–16296
    [Google Scholar]
  45. Qimron U., Madar N., Mittrucker H. W., Zilka A., Yosef I., Bloushtain N., Kaufmann S. H., Rosenshine I., Apte R. N., Porgador A.. 2004; Identification of Salmonella typhimurium genes responsible for interference with peptide presentation on MHC class I molecules: Δ yej Salmonella mutants induce superior CD8+ T-cell responses. Cell Microbiol6:1057–1070
    [Google Scholar]
  46. Rosenberger C. M., Finlay B. B.. 2002; Macrophages inhibit Salmonella typhimurium replication through MEK/ERK kinase and phagocyte NADPH oxidase activities. J Biol Chem277:18753–18762
    [Google Scholar]
  47. Rosenberger C. M., Gallo R. L., Finlay B. B.. 2004; Interplay between antibacterial effectors: a macrophage antimicrobial peptide impairs intracellular Salmonella replication. Proc Natl Acad Sci U S A101:2422–2427
    [Google Scholar]
  48. Salzman N. H., Ghosh D., Huttner K. M., Paterson Y., Bevins C. L.. 2003; Protection against enteric salmonellosis in transgenic mice expressing a human intestinal defensin. Nature422:522–526
    [Google Scholar]
  49. Sawyer J. G., Martin N. L., Hancock R. E.. 1988; Interaction of macrophage cationic proteins with the outer membrane of Pseudomonas aeruginosa . Infect Immun56:693–698
    [Google Scholar]
  50. Schauser K., Olsen J. E., Larsson L. I.. 2004; Immunocytochemical studies of Salmonella typhimurium invasion of porcine jejunal epithelial cells. J Med Microbiol53:691–695
    [Google Scholar]
  51. Shafer W. M., Qu X., Waring A. J., Lehrer R. I.. 1998; Modulation of Neisseria gonorrhoeae susceptibility to vertebrate antibacterial peptides due to a member of the resistance/nodulation/division efflux pump family. Proc Natl Acad Sci U S A95:1829–1833
    [Google Scholar]
  52. Shai Y.. 2002; From innate immunity to de-novo designed antimicrobial peptides. Curr Pharm Des8:715–725
    [Google Scholar]
  53. Shimoda M., Ohki K., Shimamoto Y., Kohashi O.. 1995; Morphology of defensin-treated Staphylococcus aureus . Infect Immun63:2886–2891
    [Google Scholar]
  54. Singh P. K., Jia H. P., Wiles K., Hesselberth J., Liu L., Conway B. A., Greenberg E. P., Valore E. V., Welsh M. J.. other authors 1998; Production of β -defensins by human airway epithelia. Proc Natl Acad Sci U S A95:14961–14966
    [Google Scholar]
  55. Smith A. C., Cirulis J. T., Casanova J. E., Scidmore M. A., Brumell J. H.. 2005; Interaction of the Salmonella -containing vacuole with the endocytic recycling system. J Biol Chem280:24634–24641
    [Google Scholar]
  56. Stumpe S., Bakker E. P.. 1997; Requirement of a large K+-uptake capacity and of extracytoplasmic protease activity for protamine resistance of Escherichia coli . Arch Microbiol167:126–136
    [Google Scholar]
  57. Stumpe S., Schmid R., Stephens D. L., Georgiou G., Bakker E. P.. 1998; Identification of OmpT as the protease that hydrolyzes the antimicrobial peptide protamine before it enters growing cells of Escherichia coli . J Bacteriol180:4002–4006
    [Google Scholar]
  58. Treptow N. A., Shuman H. A.. 1988; Allele-specific malE mutations that restore interactions between maltose-binding protein and the inner-membrane components of the maltose transport system. J Mol Biol202:809–822
    [Google Scholar]
  59. Yrlid U., Wick M. J.. 2000; Salmonella -induced apoptosis of infected macrophages results in presentation of a bacteria-encoded antigen after uptake by bystander dendritic cells. J Exp Med191:613–624
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.2007/011114-0
Loading
/content/journal/micro/10.1099/mic.0.2007/011114-0
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error