Skip to main content

Advertisement

SpringerLink
Log in

Identification and characterization of a novel outer membrane protein receptor required for hemin utilization in Vibrio vulnificus

  • Published:
BioMetals Aims and scope Submit manuscript

Abstract

Vibrio vulnificus, the cause of septicemia and serious wound infection in humans and fishes, require iron for its pathogenesis. Hemin uptake through the outer membrane receptor, HupA, is one of its many mechanisms by which it acquires iron. We report here the identification of an additional TonB-dependent hemin receptor HvtA, that is needed in conjunction with the HupA protein for optimal hemin utilization. The HvtA protein is significantly homologous to other outer membrane hemin receptors and its expression in trans restored the uptake of hemin and hemoglobin, the latter to a weaker extent, in a mutant strain that was defective in both receptors. Quantitative RT-PCR suggested that transcription of the hvtA gene was iron regulated. The operon containing the hvtA gene is homologous to the operon in V. cholerae containing the hemin receptor gene hutR suggesting a vertical transmission of the hvtA cluster from V. cholerae to V. vulnificus.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Alice AF, Naka H, Crosa JH (2008) Global gene expression as a function of the iron status of the bacterial cell: influence of differentially expressed genes in the virulence of the human pathogen Vibrio vulnificus. Infect Immun 76:4019–4037

    Article  PubMed  CAS  Google Scholar 

  • Amaro C, Biosca EG, Fouz B, Alcaide E, Esteve C (1995) Evidence that water transmits Vibrio vulnificus biotype 2 infections to eels. Appl Environ Microbiol 61:1133–1137

    PubMed  CAS  Google Scholar 

  • Bracken CS, Baer MT, Abdur-Rashid A, Helms W, Stojiljkovic I (1999) Use of heme-protein complexes by the Yersinia enterocolitica HemR receptor: histidine residues are essential for receptor function. J Bacteriol 181:6063–6072

    PubMed  CAS  Google Scholar 

  • Crosa JH (1980) A plasmid associated with virulence in the marine fish pathogen Vibrio anguillarum specifies an iron-sequestering system. Nature 284:566–568

    Article  PubMed  CAS  Google Scholar 

  • Crosa JH, Hodges LL (1981) Outer membrane proteins induced under conditions of iron limitation in the marine fish pathogen Vibrio anguillarum 775. Infect Immun 31:223–227

    PubMed  CAS  Google Scholar 

  • Figurski DH, Helinski DR (1979) Replication of an origin-containing derivative of plasmid RK2 dependent on a plasmid function provided in trans. Proc Natl Acad Sci USA 76:1648–1652

    Article  PubMed  CAS  Google Scholar 

  • Gulig PA, Bourdage KL, Starks AM (2005) Molecular Pathogenesis of Vibrio vulnificus. J Microbiol 43:118–131

    PubMed  CAS  Google Scholar 

  • Helms SD, Oliver JD, Travis JC (1984) Role of heme compounds and haptoglobin in Vibrio vulnificus pathogenicity. Infect Immun 45:345–349

    PubMed  CAS  Google Scholar 

  • Hlady WG, Klontz KC (1996) The epidemiology of Vibrio infections in Florida, 1981–1993. J Infect Dis 173:1176–1183

    Article  PubMed  CAS  Google Scholar 

  • Kim YR, Rhee JH (2003) Flagellar basal body flg operon as a virulence determinant of Vibrio vulnificus. Biochem Biophys Res Commun 304:405–410

    Article  CAS  Google Scholar 

  • Kothary MH, Kreger AS (1987) Purification and characterization of an elastolytic protease of Vibrio vulnificus. J Gen Microbiol 133:1783–1791

    PubMed  CAS  Google Scholar 

  • Lee JH, Rho JB, Park KJ, Kim CB, Han YS, Choi SH, Lee KH, Park SJ (2004) Role of flagellum and motility in pathogenesis of Vibrio vulnificus. Infect Immun 72:4905–4910

    Article  PubMed  CAS  Google Scholar 

  • Lee JH, Kim MW, Kim BS, Kim SM, Lee BC, Kim TS, Choi SH (2007) Identification and characterization of the Vibrio vulnificus rtxA essential for cytotoxicity in vitro and virulence in mice. J Microbiol 45:146–152

    PubMed  CAS  Google Scholar 

  • Litwin CM, Byrne BL (1998) Cloning and characterization of an outer membrane protein of Vibrio vulnificus required for heme utilization: regulation of expression and determination of the gene sequence. Infect Immun 66:3134–3141

    PubMed  CAS  Google Scholar 

  • Litwin CM, Quackenbush J (2001) Characterization of a Vibrio vulnificus LysR homologue, HupR, which regulates expression of the haem uptake outer membrane protein, HupA. Microb Pathog 31:295–307

    Article  PubMed  CAS  Google Scholar 

  • Litwin CM, Rayback TW, Skinner J (1996) Role of catechol siderophore synthesis in Vibrio vulnificus virulence. Infect Immun 64:2834–2838

    PubMed  CAS  Google Scholar 

  • Liu M, Alice AF, Naka H, Crosa JH (2007) The HlyU protein is a positive regulator of rtxA1, a gene responsible for cytotoxicity and virulence in the human pathogen Vibrio vulnificus. Infect Immun 75:3282–3289

    Article  PubMed  CAS  Google Scholar 

  • Liu M, Naka H, Crosa JH (2009) HlyU acts as an H-NS antirepressor in the regulation of the RTX toxin gene essential for the virulence of the human pathogen Vibrio vulnificus CMCP6. Mol Microbiol 72:491–505

    Article  PubMed  CAS  Google Scholar 

  • Mey AR, Payne SM (2001) Haem utilization in Vibrio cholerae involves multiple TonB-dependent haem receptors. Mol Microbiol 42:835–849

    Article  PubMed  CAS  Google Scholar 

  • Milton DL, O’Toole R, Horstedt P, Wolf-Watz H (1996) Flagellin A is essential for the virulence of Vibrio anguillarum. J Bacteriol 178:1310–1319

    PubMed  CAS  Google Scholar 

  • Morales VM, Backman A, Bagdasarian M (1991) A series of wide-host-range low-copy-number vectors that allow direct screening for recombinants. Gene 97:39–47

    Article  PubMed  CAS  Google Scholar 

  • Morris JGJ (1988) Vibrio vulnificus—a new monster of the deep? Ann Intern Med 109:261–263

    PubMed  Google Scholar 

  • Nishina Y, Miyoshi S, Nagase A, Shinoda S (1992) Significant role of an exocellular protease in utilization of heme by Vibrio vulnificus. Infect Immun 60:2128–2132

    PubMed  CAS  Google Scholar 

  • Oh MH, Lee SM, Lee DH, Choi SH (2009) Regulation of the Vibrio vulnificus hupA gene by temperature alteration and cyclic AMP receptor protein and evaluation of its role in virulence. Infect Immun 77:1208–1215

    Article  PubMed  CAS  Google Scholar 

  • Okujo N, Saito M, Yamamoto S, Yoshida T, Miyoshi S, Shinoda S (1994) Structure of vulnibactin, a new polyamine-containing siderophore from Vibrio vulnificus. Biometals 7:109–116

    PubMed  CAS  Google Scholar 

  • Simon R, Priefer U, Puhler A (1983) A broad host range mobilization system for in vivo genetic-engineering-transposon mutagenesis in gram-negative bacteria. Biotechnology 1:787–796

    Google Scholar 

  • Simpson LM, Oliver JD (1983) Siderophore production by Vibrio vulnificus. Infect Immun 41:644

    PubMed  CAS  Google Scholar 

  • Smith AB, Siebeling RJ (2003) Identification of genetic loci required for capsular expression in Vibrio vulnificus. Infect Immun 71:1091–1097

    Article  PubMed  CAS  Google Scholar 

  • Strom MS, Paranjpye RN (2000) Epidemiology and pathogenesis of Vibrio vulnificus. Microbes Infect 2:177–188

    Article  PubMed  CAS  Google Scholar 

  • Struyvé M, Moons M, Tommassen J (1991) Carboxy-terminal phenylalanine is essential for the correct assembly of a bacterial outer membrane protein. J Mol Biol 218:141–148

    Article  PubMed  Google Scholar 

  • Wandersman C, Delepelaire P (2004) Bacterial iron sources: from siderophores to hemophores. Annu Rev Microbiol 58:611–647

    Article  PubMed  CAS  Google Scholar 

  • Webster AC, Litwin CM (2000) Cloning and characterization of vuuA, a gene encoding the Vibrio vulnificus ferric vulnibactin receptor. Infect Immun 68:526–534

    Article  PubMed  CAS  Google Scholar 

  • Wright AC, Simpson LM, Oliver JD (1981) Role of iron in the pathogenesis of Vibrio vulnificus infections. Infect Immun 34:503–507

    PubMed  CAS  Google Scholar 

  • Wright AC, Powell JL, Tanner MK, Ensor LA, Karpas AB, Morris JG Jr, Sztein MB (1999) Differential expression of Vibrio vulnificus capsular polysaccharide. Infect Immun 67:2250–2257

    PubMed  CAS  Google Scholar 

  • Yu NY, Wagner JR, Laird MR, Melli G, Rey S, Lo R, Dao P, Sahinalp SC, Ester M, Foster LJ (2010) PSORTb 3.0: Improved protein subcellular localization prediction with refined localization subcategories and predictive capabilities for all prokaryotes. Bioinformatics 26:1608–1615

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

This project was supported by a National Institutes of Health grant AI 65981 to J.H.C.

Author information

Authors and Affiliations

  1. Department of Molecular Microbiology and Immunology, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA

    Shreya Datta & Jorge H. Crosa

Authors
  1. Shreya Datta
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jorge H. Crosa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jorge H. Crosa.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Datta, S., Crosa, J.H. Identification and characterization of a novel outer membrane protein receptor required for hemin utilization in Vibrio vulnificus . Biometals 25, 275–283 (2012). https://doi.org/10.1007/s10534-011-9501-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10534-011-9501-y

Keywords

Search

Navigation