1887

Abstract

Autotransporter protein secretion represents one of the simplest forms of secretion across Gram-negative bacterial membranes. Once secreted, autotransporter proteins either remain tethered to the bacterial surface or are released following proteolytic cleavage. Autotransporters possess a diverse array of virulence-associated functions such as motility, cytotoxicity, adherence and autoaggregation. To better understand the role of autotransporters in disease, our research focused on the autotransporters of , the aetiological agent of plague. strain CO92 has nine functional conventional autotransporters, referred to as Yaps for utotransporter roteins. Three Yaps have been directly implicated in virulence using established mouse models of plague infection (YapE, YapJ and YapK). Whilst previous studies from our laboratory have shown that most of the CO92 Yaps are cell associated, YapE and YapG are processed and released by the omptin protease Pla. In this study, we identified the Pla cleavage sites in YapG that result in many released forms of YapG in , but not in the evolutionarily related gastrointestinal pathogen, , which lacks Pla. Furthermore, we showed that YapG does not contribute to virulence in established mouse models of bubonic and pneumonic infection. As has a complex life cycle involving a wide range of mammalian hosts and a flea vector for transmission, it remains to be elucidated whether YapG has a measurable role in any other stage of plague disease.

Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.056275-0
2013-08-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jmm/62/8/1124.html?itemId=/content/journal/jmm/10.1099/jmm.0.056275-0&mimeType=html&fmt=ahah

References

  1. Agarkov A., Chauhan S., Lory P. J., Gilbertson S. R., Motin V. L. 2008; Substrate specificity and screening of the integral membrane protease Pla. Bioorg Med Chem Lett 18:427–431 [View Article][PubMed]
    [Google Scholar]
  2. Alamuri P., Mobley H. L. T. 2008; A novel autotransporter of uropathogenic Proteus mirabilis is both a cytotoxin and an agglutinin. Mol Microbiol 68:997–1017 [View Article][PubMed]
    [Google Scholar]
  3. Alamuri P., Löwer M., Hiss J. A., Himpsl S. D., Schneider G., Mobley H. L. T. 2010; Adhesion, invasion, and agglutination mediated by two trimeric autotransporters in the human uropathogen Proteus mirabilis . Infect Immun 78:4882–4894 [View Article][PubMed]
    [Google Scholar]
  4. Allsopp L. P., Totsika M., Tree J. J., Ulett G. C., Mabbett A. N., Wells T. J., Kobe B., Beatson S. A., Schembri M. A. 2010; UpaH is a newly identified autotransporter protein that contributes to biofilm formation and bladder colonization by uropathogenic Escherichia coli CFT073. Infect Immun 78:1659–1669 [View Article][PubMed]
    [Google Scholar]
  5. Allsopp L. P., Beloin C., Moriel D. G., Totsika M., Ghigo J.-M., Schembri M. A. 2012a; Functional heterogeneity of the UpaH autotransporter protein from uropathogenic Escherichia coli. . J Bacteriol 194:5769–5782 [View Article][PubMed]
    [Google Scholar]
  6. Allsopp L. P., Beloin C., Ulett G. C., Valle J., Totsika M., Sherlock O., Ghigo J.-M., Schembri M. A. 2012b; Molecular characterization of UpaB and UpaC, two new autotransporter proteins of uropathogenic Escherichia coli CFT073. Infect Immun 80:321–332 [View Article][PubMed]
    [Google Scholar]
  7. Andrews G. P., Vernati G., Ulrich R., Rocke T. E., Edwards W. H., Adamovicz J. J. 2010; Identification of in vivo-induced conserved sequences from Yersinia pestis during experimental plague infection in the rabbit. Vector Borne Zoonotic Dis 10:749–756 [View Article][PubMed]
    [Google Scholar]
  8. Bodelón G., Marín E., Fernández L. A. 2009; Role of periplasmic chaperones and BamA (YaeT/Omp85) in folding and secretion of intimin from enteropathogenic Escherichia coli strains. J Bacteriol 191:5169–5179 [View Article][PubMed]
    [Google Scholar]
  9. Bölin I., Norlander L., Wolf-Watz H. 1982; Temperature-inducible outer membrane protein of Yersinia pseudotuberculosis and Yersinia enterocolitica is associated with the virulence plasmid. Infect Immun 37:506–512[PubMed]
    [Google Scholar]
  10. Bottone E. J. 1999; Yersinia enterocolitica: overview and epidemiologic correlates. Microbes Infect 1:323–333 [View Article][PubMed]
    [Google Scholar]
  11. Cathelyn J. S., Crosby S. D., Lathem W. W., Goldman W. E., Miller V. L. 2006; RovA, a global regulator of Yersinia pestis, specifically required for bubonic plague. Proc Natl Acad Sci U S A 103:13514–13519 [View Article][PubMed]
    [Google Scholar]
  12. Chain P. S. G., Carniel E., Larimer F. W., Lamerdin J., Stoutland P. O., Regala W. M., Georgescu A. M., Vergez L. M., Land M. L. other authors 2004; Insights into the evolution of Yersinia pestis through whole-genome comparison with Yersinia pseudotuberculosis . Proc Natl Acad Sci U S A 101:13826–13831 [View Article][PubMed]
    [Google Scholar]
  13. 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]
  14. Dautin N., Bernstein H. D. 2007; Protein secretion in Gram-negative bacteria via the autotransporter pathway. Annu Rev Microbiol 61:89–112 [View Article][PubMed]
    [Google Scholar]
  15. Doll J. M., Zeitz P. S., Ettestad P., Bucholtz A. L., Davis T., Gage K. 1994; Cat-transmitted fatal pneumonic plague in a person who traveled from Colorado to Arizona. Am J Trop Med Hyg 51:109–114[PubMed]
    [Google Scholar]
  16. Dorsey C. W., Laarakker M. C., Humphries A. D., Weening E. H., Bäumler A. J. 2005; Salmonella enterica serotype Typhimurium MisL is an intestinal colonization factor that binds fibronectin. Mol Microbiol 57:196–211 [View Article][PubMed]
    [Google Scholar]
  17. Elder K. D., Harvill E. T. 2004; Strain-dependent role of BrkA during Bordetella pertussis infection of the murine respiratory tract. Infect Immun 72:5919–5924 [View Article][PubMed]
    [Google Scholar]
  18. Felek S., Lawrenz M. B., Krukonis E. S. 2008; The Yersinia pestis autotransporter YapC mediates host cell binding, autoaggregation and biofilm formation. Microbiology 154:1802–1812 [View Article][PubMed]
    [Google Scholar]
  19. Ferber D. M., Brubaker R. R. 1981; Plasmids in Yersinia pestis . Infect Immun 31:839–841[PubMed]
    [Google Scholar]
  20. 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 issueD211–D222 [View Article][PubMed]
    [Google Scholar]
  21. Henderson I. R., Nataro J. P. 2001; Virulence functions of autotransporter proteins. Infect Immun 69:1231–1243 [View Article][PubMed]
    [Google Scholar]
  22. Henderson I. R., Navarro-Garcia F., Nataro J. P. 1998; The great escape: structure and function of the autotransporter proteins. Trends Microbiol 6:370–378 [View Article][PubMed]
    [Google Scholar]
  23. Henderson I. R., Navarro-Garcia F., Desvaux M., Fernandez R. C., Ala’Aldeen D. 2004; Type V protein secretion pathway: the autotransporter story. Microbiol Mol Biol Rev 68:692–744 [View Article][PubMed]
    [Google Scholar]
  24. Higuchi K., Smith J. L. 1961; Studies on the nutrition and physiology of Pasteurella pestis. VI. A differential plating medium for the estimation of the mutation rate to avirulence. J Bacteriol 81:605–608[PubMed]
    [Google Scholar]
  25. Hinnebusch B. J. 1997; Bubonic plague: a molecular genetic case history of the emergence of an infectious disease. J Mol Med (Berl) 75:645–652 [View Article][PubMed]
    [Google Scholar]
  26. Janssen W. A., Fukui G. M., Surgalla M. J. 1958; A study of the fate of Pasteurella pestis following intracardial injection into guinea pigs. J Infect Dis 103:183–187 [View Article][PubMed]
    [Google Scholar]
  27. Jong W. S. P., ten Hagen-Jongman C. M., Ruijter E., Orru R. V., Genevaux P., Luirink J. 2010; YidC is involved in the biogenesis of the secreted autotransporter hemoglobin protease. J Biol Chem 285:39682–39690 [View Article][PubMed]
    [Google Scholar]
  28. Kai-Larsen Y., Lüthje P., Chromek M., Peters V., Wang X., Holm Å., Kádas L., Hedlund K.-O., Johansson J. other authors 2010; Uropathogenic Escherichia coli modulates immune responses and its curli fimbriae interact with the antimicrobial peptide LL-37. PLoS Pathog 6:e1001010 [View Article][PubMed]
    [Google Scholar]
  29. Kukkonen M., Lähteenmäki K., Suomalainen M., Kalkkinen N., Emödy L., Lång H., Korhonen T. K. 2001; Protein regions important for plasminogen activation and inactivation of α2-antiplasmin in the surface protease Pla of Yersinia pestis . Mol Microbiol 40:1097–1111 [View Article][PubMed]
    [Google Scholar]
  30. Lähteenmäki K., Kuusela P., Korhonen T. K. 2001; Bacterial plasminogen activators and receptors. FEMS Microbiol Rev 25:531–552[PubMed] [CrossRef]
    [Google Scholar]
  31. Lathem W. W., Crosby S. D., Miller V. L., Goldman W. E. 2005; Progression of primary pneumonic plague: a mouse model of infection, pathology, and bacterial transcriptional activity. Proc Natl Acad Sci U S A 102:17786–17791 [View Article][PubMed]
    [Google Scholar]
  32. Lathem W. W., Price P. A., Miller V. L., Goldman W. E. 2007; A plasminogen-activating protease specifically controls the development of primary pneumonic plague. Science 315:509–513 [View Article][PubMed]
    [Google Scholar]
  33. Lawrenz M. B., Lenz J. D., Miller V. L. 2009; A novel autotransporter adhesin is required for efficient colonization during bubonic plague. Infect Immun 77:317–326 [View Article][PubMed]
    [Google Scholar]
  34. Lenz J. D., Lawrenz M. B., Cotter D. G., Lane M. C., Gonzalez R. J., Palacios M., Miller V. L. 2011; Expression during host infection and localization of Yersinia pestis autotransporter proteins. J Bacteriol 193:5936–5949 [View Article][PubMed]
    [Google Scholar]
  35. Lenz J. D., Temple B. R. S., Miller V. L. 2012; Evolution and virulence contributions of the autotransporter proteins YapJ and YapK of Yersinia pestis CO92 and their homologs in Y. pseudotuberculosis IP32953. Infect Immun 80:3693–3705 [View Article][PubMed]
    [Google Scholar]
  36. Letunic I., Doerks T., Bork P. 2012; SMART 7: recent updates to the protein domain annotation resource. Nucleic Acids Res 40:Database issueD302–D305 [View Article][PubMed]
    [Google Scholar]
  37. Marchler-Bauer A., Lu S., Anderson J. B., Chitsaz F., Derbyshire M. K., DeWeese-Scott C., Fong J. H., Geer L. Y., Geer R. C. other authors 2011; CDD: a Conserved Domain Database for the functional annotation of proteins. Nucleic Acids Res 39:Database issueD225–D229 [View Article][PubMed]
    [Google Scholar]
  38. McCarter J. D., Stephens D., Shoemaker K., Rosenberg S., Kirsch J. F., Georgiou G. 2004; Substrate specificity of the Escherichia coli outer membrane protease OmpT. J Bacteriol 186:5919–5925 [View Article][PubMed]
    [Google Scholar]
  39. Melican K., Sandoval R. M., Kader A., Josefsson L., Tanner G. A., Molitoris B. A., Richter-Dahlfors A. 2011; Uropathogenic Escherichia coli P and Type 1 fimbriae act in synergy in a living host to facilitate renal colonization leading to nephron obstruction. PLoS Pathog 7:e1001298 [View Article][PubMed]
    [Google Scholar]
  40. Naktin J., Beavis K. G. 1999; Yersinia enterocolitica and Yersinia pseudotuberculosis . Clin Lab Med 19:523–536, vi[PubMed]
    [Google Scholar]
  41. Noofeli M., Bokhari H., Blackburn P., Roberts M., Coote J. G., Parton R. 2011; BapC autotransporter protein is a virulence determinant of Bordetella pertussis . Microb Pathog 51:169–177 [View Article][PubMed]
    [Google Scholar]
  42. Obrist M. W., Miller V. L. 2012; Low copy expression vectors for use in Yersinia sp. and related organisms. Plasmid 68:33–42 [View Article][PubMed]
    [Google Scholar]
  43. Ong C.-L. Y., Ulett G. C., Mabbett A. N., Beatson S. A., Webb R. I., Monaghan W., Nimmo G. R., Looke D. F., McEwan A. G., Schembri M. A. 2008; Identification of type 3 fimbriae in uropathogenic Escherichia coli reveals a role in biofilm formation. J Bacteriol 190:1054–1063 [View Article][PubMed]
    [Google Scholar]
  44. Parkhill J., Wren B. W., Thomson N. R., Titball R. W., Holden M. T., Prentice M. B., Sebaihia M., James K. D., Churcher C. other authors 2001; Genome sequence of Yersinia pestis, the causative agent of plague. Nature 413:523–527 [View Article][PubMed]
    [Google Scholar]
  45. Perry R. D., Fetherston J. D. 1997; Yersinia pestis – etiologic agent of plague. Clin Microbiol Rev 10:35–66[PubMed]
    [Google Scholar]
  46. Rakin A., Boolgakowa E., Heesemann J. 1996; Structural and functional organization of the Yersinia pestis bacteriocin pesticin gene cluster. Microbiology 142:3415–3424 [View Article][PubMed]
    [Google Scholar]
  47. Rollins S. E., Rollins S. M., Ryan E. T. 2003; Yersinia pestis and the plague. Am J Clin Pathol 119:Suppl.S78–S85[PubMed]
    [Google Scholar]
  48. Roy K., Kansal R., Bartels S. R., Hamilton D. J., Shaaban S., Fleckenstein J. M. 2011; Adhesin degradation accelerates delivery of heat-labile toxin by enterotoxigenic Escherichia coli. . J Biol Chem 286:29771–29779 [View Article][PubMed]
    [Google Scholar]
  49. Ruiz-Perez F., Henderson I. R., Leyton D. L., Rossiter A. E., Zhang Y., Nataro J. P. 2009; Roles of periplasmic chaperone proteins in the biogenesis of serine protease autotransporters of Enterobacteriaceae . J Bacteriol 191:6571–6583 [View Article][PubMed]
    [Google Scholar]
  50. Ruiz-Perez F., Henderson I. R., Nataro J. P. 2010; Interaction of FkpA, a peptidyl-prolyl cis/trans isomerase with EspP autotransporter protein. Gut Microbes 1:339–344 [View Article][PubMed]
    [Google Scholar]
  51. Sambrook J., Russell D. W. 2001; Protocol 3: In vitro mutagenesis using double stranded DNA templates: selection of mutants with DpnI. In Molecular Cloning: a Laboratory Manual, 3rd edn. pp. 13.19–13.25 Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press;
    [Google Scholar]
  52. Sauri A., Soprova Z., Wickström D., de Gier J.-W., Van der Schors R. C., Smit A. B., Jong W. S. P., Luirink J. 2009; The Bam (Omp85) complex is involved in secretion of the autotransporter haemoglobin protease. Microbiology 155:3982–3991 [View Article][PubMed]
    [Google Scholar]
  53. Schembri M. A., Dalsgaard D., Klemm P. 2004; Capsule shields the function of short bacterial adhesins. J Bacteriol 186:1249–1257 [View Article][PubMed]
    [Google Scholar]
  54. Sebbane F., Gardner D., Long D., Gowen B. B., Hinnebusch B. J. 2005; Kinetics of disease progression and host response in a rat model of bubonic plague. Am J Pathol 166:1427–1439 [View Article][PubMed]
    [Google Scholar]
  55. Sebbane F., Jarrett C. O., Gardner D., Long D., Hinnebusch B. J. 2006; Role of the Yersinia pestis plasminogen activator in the incidence of distinct septicemic and bubonic forms of flea-borne plague. Proc Natl Acad Sci U S A 103:5526–5530 [View Article][PubMed]
    [Google Scholar]
  56. Sodeinde O. A., Goguen J. D. 1989; Nucleotide sequence of the plasminogen activator gene of Yersinia pestis: relationship to ompT of Escherichia coli and gene E of Salmonella typhimurium . Infect Immun 57:1517–1523[PubMed]
    [Google Scholar]
  57. Spurbeck R. R., Stapleton A. E., Johnson J. R., Walk S. T., Hooton T. M., Mobley H. L. T. 2011; Fimbrial profiles predict virulence of uropathogenic Escherichia coli strains: contribution of Ygi and Yad fimbriae. Infect Immun 79:4753–4763 [View Article][PubMed]
    [Google Scholar]
  58. Suomalainen M., Haiko J., Ramu P., Lobo L., Kukkonen M., Westerlund-Wikström B., Virkola R., Lähteenmäki K., Korhonen T. K. 2007; Using every trick in the book: the Pla surface protease of Yersinia pestis . Adv Exp Med Biol 603:268–278 [View Article][PubMed]
    [Google Scholar]
  59. Ulett G. C., Mabbett A. N., Fung K. C., Webb R. I., Schembri M. A. 2007a; The role of F9 fimbriae of uropathogenic Escherichia coli in biofilm formation. Microbiology 153:2321–2331 [View Article][PubMed]
    [Google Scholar]
  60. Ulett G. C., Valle J., Beloin C., Sherlock O., Ghigo J.-M., Schembri M. A. 2007b; Functional analysis of antigen 43 in uropathogenic Escherichia coli reveals a role in long-term persistence in the urinary tract. Infect Immun 75:3233–3244 [View Article][PubMed]
    [Google Scholar]
  61. Valle J., Mabbett A. N., Ulett G. C., Toledo-Arana A., Wecker K., Totsika M., Schembri M. A., Ghigo J.-M., Beloin C. 2008; UpaG, a new member of the trimeric autotransporter family of adhesins in uropathogenic Escherichia coli . J Bacteriol 190:4147–4161 [View Article][PubMed]
    [Google Scholar]
  62. Viboud G. I., Bliska J. B. 2005; Yersinia outer proteins: role in modulation of host cell signaling responses and pathogenesis. Annu Rev Microbiol 59:69–89 [View Article][PubMed]
    [Google Scholar]
  63. Walker K. A., Miller V. L. 2004; Regulation of the Ysa type III secretion system of Yersinia enterocolitica by YsaE/SycB and YsrS/YsrR. J Bacteriol 186:4056–4066 [View Article][PubMed]
    [Google Scholar]
  64. Wang X., Preston J. F. III, Romeo T. 2004; The pgaABCD locus of Escherichia coli promotes the synthesis of a polysaccharide adhesin required for biofilm formation. J Bacteriol 186:2724–2734 [View Article][PubMed]
    [Google Scholar]
  65. Wren B. W. 2003; The yersiniae – a model genus to study the rapid evolution of bacterial pathogens. Nat Rev Microbiol 1:55–64 [View Article][PubMed]
    [Google Scholar]
  66. Zdobnov E. M., Apweiler R. 2001; InterProScan – an integration platform for the signature-recognition methods in InterPro. Bioinformatics 17:847–848 [View Article][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.056275-0
Loading
/content/journal/jmm/10.1099/jmm.0.056275-0
Loading

Data & Media loading...

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