Molecular Pathogenesis of Vibrio vulnificus

  • Gulig Paul A. (Department of Molecular Genetics and Microbiology, University of Florida College of Medicine) ;
  • Bourdage Keri L. (Department of Molecular Genetics and Microbiology, University of Florida College of Medicine) ;
  • Starks Angela M. (Department of Molecular Genetics and Microbiology, University of Florida College of Medicine)
  • Published : 2005.02.28

Abstract

Vibrio vulnificus is an opportunistic pathogen of humans that has the capability of causing rare, yet devastating disease. The bacteria are naturally present in estuarine environments and frequently contaminate seafoods. Within days of consuming uncooked, contaminated seafood, predisposed individuals can succumb to sepsis. Additionally, in otherwise healthy people, V. vulnificus causes wound infection that can require amputation or lead to sepsis. These diseases share the characteristics that the bacteria multiply extremely rapidly in host tissues and cause extensive damage. Despite the analysis of virulence for over 20 years using a combination of animal and cell culture models, surprisingly little is known about the mechanisms by which V. vulnificus causes disease. This is in part because of differences observed using animal models that involve infection with bacteria versus injection of toxins. However, the increasing use of genetic analysis coupled with detailed animal models is revealing new insight into the pathogenesis of V. vulnificus disease.

Keywords

References

  1. Ashrafian, H. 2003. Hepcidin: the missing link between hemochromatosis and infections. Infect. Immun. 71, 6693-6700.
  2. Bang, YB., S.E. Lee, J.H. Rhee, and S.H. Choi. 1999. Evidence that expression of the Vibrio vulnificus hemolysin gene is dependent on cyclic AMP and cyclic AMP receptor protein. J. Bacteriol. 181,7639-7642.
  3. Biosca, E.G, B. Fouz, E. Alcaide, and e. Amaro. 1996a. Siderophore-mediated iron acquisition mechanisms in Vibrio vulnificus biotype 2. Appl. Environ. Microbiol. 62, 928-935.
  4. Biosca, E.G, J.D. Oliver, and C. Amaro. 1996b. Phenotypic characterization of Vibrio vulnificus biotype 2, a lipopolysaccharide-based homogeneous 0 serogroup within Vibrio vulnificus. Appl. Environ. Microbiol. 62, 918-927.
  5. Bisharat, N., V. Agmon, R Finkelstein, R Raz, G. Ben Dror, L.Lerner, S. Soboh, R Colodner, D.N. Cameron, D.L. Wykstra, D.L. Swerdlow, and 1.1. Farmer, III. 1999. Clinical, epidemiological, and microbiological features of Vibrio vulnificus biogroup 3 causing outbreaks of wound infection and bacteraemia in Israel. Israel Vibrio Study Group. Lancet. 354, 1421-1424.
  6. Blake, P.A., M.H. Merson, RE. Weaver, D.G. Hollis, and nc Heublein. 1979. Disease caused by a marine Vibrio. Clinical characteristics and epidemiology. N. Engl. J. Med. 300, 1-5.
  7. Bourdage, K, S.-S. Lang, and P. Gulig. 2002. Virulence of Vibrio vulnificus is not related to source of the strain or cytotoxicity in INT-407 cell culture models. Abstr. Z-21, p. 511. Abstr. Annu. Meet. Am. Soc. Microbiol.
  8. Bourdage, K, A Starks, and P Gulig. 2003. The RtxA toxin is a major cytotoxic factor but plays a minor role in virulence of Vibrio vulnificus. Abstr. B-58, Abstr. Annu. Meet. Am. Soc. Microbiol.
  9. Bowdre, J.H., M.D. Poole, and J.D. Oliver. 1981. Edema and hemoconcentrationin mice experimentally infected with Vibrio vulnificus. Infect. Immun. 32, 1193-1199.
  10. Brennaman, B., D. Soucy, and R.I. Howard. 1987. Effect of iron and liver injury on the pathogenesis of Vibrio vulnificus. J. Surg. Res. 43, 527-531.
  11. Buchrieser, C; v.v. Gangar, R.L. Murphree, M.L. Tamplin, and e.w. Kaspar. 1995. MUltiple Vibrio vulnificus strains in oysters as demonstrated by clamped homogeneous electric field gel electrophoresis. Appl. Environ. Microbiol. 61, 1163-1168.
  12. Bullen, 1.1., PB. Spalding, c.o Ward, and J.M. Gutteridge. 1991. Hemochromatosis, iron and septicemia caused by Vibrio vulnificus. Arch. Intern. Med. 151, 1606-1609.
  13. Bush, e.A., P Patel, S. Gunawardena, J. Powell, A Joseph, J.A Johnson, and J.G Morris. 1997. Classification of Vibrio vulnificus strains by the carbohydrate composition of their capsular polysaccharides. Anal. Biochem. 250, 186-195.
  14. Cerveny, KE., A. DePaola, D.H. Duckworth, and P.A. Gulig. 2002. Phage therapy of local and systemic disease caused by Vibrio vulnificus in iron dextran-treated mice. Infect. Immun. 70, 6251-6262.
  15. Chang, T.M., Y.e. Chuang, J.H. Su, and M.e. Chang. 1997. Cloning and sequence analysis of a novel hemolysin gene (vllY) from Vibrio vulnificus. Appl. Environ. Microbiol. 63, 38513857.
  16. Chen, C.Y, KM. Wu, vc. Chang, C.H. Chang, n.c Tsai, T.L. Liao, YM. Liu, HJ. Chen, AB. Shen, rc Li, T.L. Su, c.r. Shao, c.r Lee, L.I. Hor, and S.F Tsai. 2003. Comparative genome analysis of Vibrio vulnificus, a marine pathogen. Genome Res. 13, 2577-2587.
  17. Chen, Ye., M.e. Chang, ye. Chuang, and C.L. Jeang. 2004a. Characterization and virulence of hemolysin III from Vibrio vulnificus. Curro Microbiol. 49, 175-179.
  18. Chen, Ye., ye. Chuang, e.e. Chang, e.L. Jeang, and M.e. Chang. 2004b. A K+ yptake protein, TrkA, is required for serum, protamine, and polymyxin B resistance in Vibrio vulnificus. Infect. Immun. 72, 629-636.
  19. Cheng, J.C., e.P Shao, and L.I. Hor. 1996. Cloning and nucleotide sequencing of the protease gene of Vibrio vulnificus. Gene. 183, 255-257.
  20. Choi, H.K, N.Y Park, D.I. Kim, HJ. Chung, S. Ryu, and S.H. Choi. 2002. Promoter analysis and regulatory characteristics of vvhBA encoding cytolytic hemolysin of Vibrio vulnificus. J. Biol. Chem. 277,47292-47299.
  21. Chuang, YC; T.M. Chang, and M.C. Chang. 1997. Cloning and characterization of the gene (emp V) encoding extracellular metalloprotease from Vibrio vulnificus. Gene. 189, 163-168.
  22. DePaola, A, J.L. Nordstrom, A Dalsgaard, A Forslund, J.D. Oliver, T. Bates, KL. Bourdage, and P.A. Gulig. 2003. Analysis of Vibrio vulnificus from market oysters and septicemia cases for virulence markers. Appl. Environ. Microbiol. 69, 4006-4011.
  23. Desmond, E.P., J.M. Janda, FI. Adams, and EJ. Bottone. 1984. Comparative studies and laboratory diagnosis of Vibrio vulnificus, an invasive Vibrio sp. J. Clin. Microbiol. 19, 122-125.
  24. Devi, S.I., U. Hayat, c.e. Frasch, AS. Kreger, and J.G. Morris, Jr. 1995. Capsular polysaccharide-protein conjugate vaccines of carbotype I Vibrio vulnificus: construction, immunogenicity, and protective efficacy in a murine model. Infect. Immun. 63, 2906-2911.
  25. Devi, S.J., U. Hayat, J.L. Powell, and J.G Morris, Jr. 1996. Preclinical immunoprophylactic and immunotherapeutic efficacy of antisera to capsular polysaccharide-tetanus toxoid conjugate vaccines of Vibrio vulnificus. Infect. Immun. 64, 2220-2224.
  26. Duckworth, D.H. and P.A. Gulig. 2001. Bacteriophages: Potential treatment for bacterial infections. BioDrugs. 16, 57-62.
  27. Falkow, S. 1988. Molecular Koch's postulates applied to microbial pathogenicity. Rev. Infect. Dis. 10, S274-S276.
  28. Fan, J.1., c.r- Shao, Y.c. Ho, C.K. Yu, and L.L Hor. 2001. Isolation and characterization of a Vibrio vulnificus mutant deficient in both extracellular metalloprotease and cytolysin. Infect. Immun. 69, 5943-5948.
  29. Food and Nutrition Board - Institute of Medicine. 1991. EE. Ahmed (ed), Seafood Safety/Committee on Evaluation of the Safety of Fishery Products. National Academy Press, Washington, D.C.
  30. Fouz, B., R Mazoy, E Vazquez, M.L. Lemos, and C. Amaro. 1997. Isolation of a hemin and hemoglobin binding outer membrane protein of Vibrio vulnificus biotype 2 (serogroup E). FEMS Microbial. Lett. 156, 187-191.
  31. Gallman, AM., D.H. Duckworth, S.c. Skinner, T.1. Doyle, and PA Gulig. 1999. Both virulent and naturally attenuated Vibrio vulnificus strains are cytotoxic for, but non-invasive into, human intestinal epithelial cell lines. Abstr. B-304, p. 268. Abstr: Annu. Meet. Am. Soc. Microbial.
  32. Gander, R.M. and M.T LaRocco. 1989. Detection of piluslike structures on clinical and environmental isolates of Vibrio vulnificus. J. Clin. Microbial. 27, 1015-1021.
  33. Gray, L.D. and AS. Kreger. 1985. Purification and characterization of an extracellular cytolysin produced by Vibrio vulnificus. Infect. Immun. 48, 62-72.
  34. Gray, L.D. and AS. Kreger. 1986. Detection of anti-Vibrio vulnificus cytolysin antibodies in sera from mice and a human surviving Vibrio vulnificus disease. Infect. Immun. 51, 964-965.
  35. Gray, L.D. and AS. Kreger. 1987. Mouse skin damage caused by cytolysin from Vibrio vulnificus and by V. vulnificus infection. J. Infect. Dis. 155, 236-241.
  36. Gray, L.D. and A.S. Kreger. 1989. Detection of Vibrio vulnificus cytolysin in V. vulnificus-infected mice. Toxicon. 27, 439-464.
  37. Gulig, PA 1993. Use of isogenic mutants to study bacterial virulence factors. J. Microbial. Methods. 18, 275-287.
  38. Halow, KD., RC. Harner, and LJ. Fontenelle. 1996. Primary skin infections secondary to Vibrio vulnificus: the role of operative intervention. J. Am. Call. Surg. 183, 329-334.
  39. Handfield, M., L.1. Brady, A Progulske-Fox, and J.D. Hillman. 2000. IVIAT: a novel method to identify microbial genes expressed specifically during human infections. Trends Microbial. 8, 336-339.
  40. Helms, S.D., J.D. Oliver, and J.c. Travis. 1984. Role of heme compoundsand haptoglobin in Vibrio vulnificus pathogenicity. Infect. Immun. 45, 345-349.
  41. Hlady, WG and KC. Klontz. 1996. The epidemiology of Vibrio infections in Florida, 1981-1993. J. Infect. Dis. 173, 1176-1183.
  42. Hlady, WG, R.C. Mullen, and RS. Hopkin. 1993. Vibrio vulnificus from raw oysters. Leading cause of reported deaths from foodborne illness in Florida. 1. Fla. Med. Assoc. 80, 536-538.
  43. Hor, L.I., Y.K Chang, c.c. Chang, H.Y. Lei, and J.T Ou. 2000. Mechanism of high susceptibility of iron-overloaded mouse to Vibrio vulnificus infection. Microbial. Immunol. 44, 871-878.
  44. Hor, L.L, C.T Gao, and L. Wan. 1995. Isolation and characterization of Vibrio vulnificus inhabiting the marine environment of the southwestern area of Taiwan. 1. Biomed. Sci. 2, 384-389.
  45. Hsueh, P.R., C.Y. Lin, H.J. Tang, H.C. Lee, J.W Liu, Y.C. Liu, and Y.c. Chuang. 2004. Vibrio vulnificus in Taiwan. Emerg. Infect. Dis. 10, 1363-1368.
  46. Hulsmann, A, TM. Rosche, LS. Kong, H.M. Hassan, D.M. Beam, and J.D. Oliver. 2003. RpoS-dependent stress response and exoenzyme production in Vibrio vulnificus. Appl. Environ. Microbial. 69, 6114-6120.
  47. Jackson, J.K., RL. Murphree, and M.L. Tamplin. 1997. Evidence that mortality from Vibrio vulnificus infection results from single strains among heterogeneous populations in shellfish. J. Clin. Microbial. 35, 2098-2101.
  48. Jeong, H.S., KC. Jeong, H.K. Choi, K.1. Park, K.H. Lee, J.H. Rhee, and S.H. Choi. 2001. Differential expression of Vibrio vulnificus elastase gene in a growth phase-dependent manner by two different types of promoters. J. Biol. Chem. 276, 13875-13880.
  49. Jeong, H.S., M.H. Lee, KH. Lee, S.J. Park, and S.H. Choi. 2003. SmcR and cyclic AMP receptor protein coactivate Vibrio vulnificus vvpE encoding elastase through the RpoS-dependent promoter in a synergistic manner. 1. Bioi. Chon. 278, 4507245081.
  50. Jeong, KC., H.S. Jeong, J.H. Rhee, S.E. Lee, S.S. Chung, AM. Starks, GM. Escudero, PA. Gulig, and S.H. Choi. 2000. Construction and phenotypic evaluation of a Vibrio vulnificus vvpE mutant for elastolytie protease. Infect. Immun. 68, 5096-5106.
  51. Johnson, D.E. and EM. Calia. 1981. Hemolytic reaction of clinical and environmental strains of Vibrio vulnificus. J. Clin. Microbial. 14, 457-459.
  52. Joseph, L.A. and A.C. Wright. 2004. Expression of Vibrio vulnificus capsular polysaccharide inhibits biofilm formation. J. Bacterial. 186, 889-893.
  53. Kang, M.K, E.C. Jhee, B.S. Koo, J.Y. Yang, B.H. Park, J.S. Kim, H.W Rho, H.R Kim, and J.W Park. 2002. Induction of nitric oxide synthase expression by Vibrio vulnificus cytolysin. Biochem. Biophys. Res. Commun. 290, 1090-1095.
  54. Kashimoto, T, S. Ueno, M. Hanajima, H. Hayashi, Y. Akeda, S. Miyoshi, T Hongo, T Honda, and N. Susa. 2003. Vibrio vulnificus induces macrophage apoptosis in vitro and in vivo. Infect. Immun. 71, 533-535.
  55. Kawase, T, S. Miyoshi, Z. Sultan, and S. Shinoda. 2004. Regulation system for protease production in Vibrio vulnificus. FEMS Microbial. Lett. 55-59.
  56. Kaysner, C.A, C. Abeyta, Jr., M.M. Wekell, A DePaola, Jr., RE Stott, and J.M. ,Leitch. 1987. Virulent strains of Vibrio vulnificus isolated from estuaries of the United States West Coast. Appl. Environ. Microbial. 53, 1349-1351.
  57. Kim, B.S. and J.S. Kim. 2002. Vibrio vulnificus cytolysin induces hyperadhesiveness of pulmonary endothelial cells for neutrophils through endothelial P-selectin: a mechanism for pulmonary damage by Vibrio vulnificus cytolysin. Exp. Mol. Med. 34, 308-312.
  58. Kim, H.R, H.W Rho, M.H. Jeong, J.W Park, J.S. Kim, B.H. Park, U.H. Kim, and S.D. Park. 1993. Hemolytic mechanism of cytolysin produced from V. vulnificus. Life Sci. 53,571-577.
  59. Kim, S.Y., S.E. Lee, Y.R. Kim, C.M. Kim, P.Y. Ryu, RE. Choy, S.S. Chung, and 1.H. Rhee. 2003a. Regulation of Vibrio vulnificus virulence by the LuxS quorum-sensing system. Mol. Microbiol. 48, 1647-1664.
  60. Kim, Y, B. Kim, 1. Jeon, S. Kim, S. Lee, and J.H. Rhee. 2004. Analysis of the potential functional domains and identification of host binding partners of Vibrio vulnificus RtxA toxin. Abstr. B-142, Abstr. Annu. Meet. Am. Soc. Microbiol.
  61. Kim, YR., S.E. Lee, C.M. Kim, S.Y Kim, E.K Shin, D.H. Shin, S.S. Chung, H.E. Choy, A Progulske-Fox, J.D. Hillman, M. Handfield, and 1.H. Rhee. 2003b. Characterization and pathogenic significance of Vibrio vulnificus antigens preferentially expressed in septicemic patients. Infect. Immun. 71, 5461-5471.
  62. Kim, YR. and J.H. Rhee. 2003. Flagellar basal body fig operon as a virulence determinant of Vibrio vulnificus. Biochem. Biophys. Res. Commun. 304,405-410.
  63. Kook, H., S.E. Lee, YH. Baik, S.S. Chung, and 1.H. Rhee. 1996. Vibrio vulnificus hemolysin dilates rat thoracic aorta by activating guanylate cyclase. Life Sci. 59, PL41-PL47.
  64. Kothary, M.H. and A.S. Kreger. 1985. Production and partial characterization of an elastolytic protease of Vibrio vulnificus. Infect. Immun. 50, 534-540.
  65. Kothary, M.H. and AS. Kreger. 1987. Purification and characterization of an elastolytic protease of Vibrio vulnificus. 1. Cell. Microbial. 133, 1783-1791.
  66. Kraffert, C.A and DJ. Hogan. 1992. Vibrio vulnificus infection and iron overload. J. Am. Acad. Dennatol. 26, 140.
  67. Kreger, A and D. Lockwood. 1981. Detection of extracellular toxin(s) produced by Vibrio vulnificus. Infect. Immun. 33, 583-590.
  68. Krukonis, E.S. and V.I. DiRita. 2003. From motility to virulence: sensing and responding to environmental signals in Vibrio cholerae. Curro Opin. Microbiol. 6, 186-190.
  69. Kumamoto, KS. and D.J. Vukich. 1998. Clinical infections of Vibrio vulnificus: a case report and review of the literature. J. Emerg. Med. 16, 61-66.
  70. Kwon, K.B., 1.Y Yang, D.G Ryu, H.W Rho, 1.S. Kim, J.W Park, H.R. Kim, and B.H. Park. 2001. Vibrio vulnificus cytolysin induces superoxide anion-initiated apoptotic signaling pathway inhuman ECV304 cells. J. Biol. Chem. 276,47518-47523.
  71. Lally, E.T., R.B. Hill, I.R. Kieba, and r. Korostoff. 1999. The interaction between RTX toxins and target cells. Trends Microbiol. 7, 356-361.
  72. Lee, HJ., KJ. Park, A.Y Lee, S.G Park, ,s.C. Park, KH. Lee, and S.l Park. 2003a. Regulation of fur expression by RpoS and fur in Vibrio vulnificus. J. Bacteriol. 185,5891-5896.
  73. Lee, 1.H., lB. Rho, KJ. Park, C.B. Kim, YS. Han, S.H. Choi, KH. Lee, and SJ. Park. 2004a. Role of flagellum and motility in pathogenesis of Vibrio vulnificus. Infect. Immun. 72, 4905-4910.
  74. Lee, S., Y Kim, B. Kim, S. Kim, C. Kim, S. Chung, and J. Rhee. 2003b. Cytotoxic mechanisms of Vibrio vulnificus RTX toxin, a newly discovered key virulence factor. Abstr. B-57, Abstr. Annu. Meet. Am. Soc. Microbiol.
  75. Lee, S.E., P.Y Ryu, S.Y Kim, YR. Kim, J.T. Koh, OJ. Kim, S.S. Chung, H.E. Choy, and lH. Rhee. 2004b. Production of Vibrio vulnificus hemolysin in vivo and its pathogenic significance. Biochem. Biophys. Res. Commun. 324, 86-91.
  76. Lee, S.E., S.H. Shin, S.Y Kim, YR. Kim, DR Shin, S.S. Chung, Z.H. Lee, 1.Y Lee, KC. Jeong, S.H. Choi, and J.H. Rhee. 2000. Vibrio vulnificus has the transmembrane transcription activator ToxRS stimulating the expression of the hemolysin gene vvhA. 1. Bacteriol. 182,3405-3415.
  77. Lee, YR., KH. Park, za. Lin, YJ. Kho, r.w Park, H.W. Rho, B.S. Koo, H.R. Kim, E.K Song, H.N. Yu,MK Han, S.O. Lee, E.C. Jhee, and lS. Kim. 2004c. A calcium-calmodulin antagonist blocks experimental Vibrio vulnificus cytolysin-induced lethality in an experimental mouse model. Infect. Immun. 72, 6157-6159.
  78. Linkous, DA and J.D. Oliver. 1999. Pathogenesis of Vibrio vulnificus. FEMS Microbiol. Lett. 174,207-214.
  79. Litwin, C.M. and B.L. Byrne. 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.
  80. Litwin, C.M. and S.B. Calderwood. 1993. Cloning and genetic analysis of the Vibrio vulnificus fur gene and construction of a fur mutant by in vivo marker exchange. J. Bacteriol. 175, 706715.
  81. Litwin, C.M., T.W Rayback, and J. Skinner. 1996. Role of catechol siderophore synthesis in Vibrio vulnificus virulence. Infect. Immun. 64, 2834-2838.
  82. Martin, SJ. and R.I. Siebeling. 1991. Identification of Vibrio vulnificus 0 serovars with antilipopolysaccharide monoclonal antibody. J. Clin. Microbiol. 29, 1684- I688.
  83. Maruo, K, T. Akaike, T. Ono, and H. Maeda. 1998. Involvement of bradykinin generation in intravascular dissemination of Vibrio vulnificus and prevention of invasion by a bradykinin antagonist. Infect. Immun. 66, 866-869.
  84. McDougald, D., SA Rice, and S. Kjelleberg. 2001. SmcR-dependent regulation of adaptive phenotypes in Vibrio vulnificus. J. Bacteriol. 183, 758-762.
  85. Miller, M.B. and B.L. Bassler. 2001. Quorum sensing in bacteria. Ann. Rev. Microbiol. 55, 165-199.
  86. Miyoshi, N., C. Shimizu, S. Miyoshi, and S. Shinoda. 1987. Purification and characterization of Vibrio vulnificus protease. Microbiol. Immunol. 31, 13-25.
  87. Miyoshi, S. and S. Shinoda. 1988. Role of the protease in the permeability enhancement by Vibrio vulnificus. Microbiol. Immunolo 32, 1025-1032.
  88. Miyoshi, S. and S. Shinoda. 1992. Activation mechanism of human Hageman factor-plasma kallikrein- kinin system by Vibrio vulnificus metalloprotease. FEBS Lett. 308, 3I5-3 19.
  89. Molla, A, T. Yamamoto, T. Akaike, S. Miyoshi, and H. Maeda. 1989. Activation of hageman factor and prekallikrein and generation of kinin by various microbial proteinases. J. Biol. Chem. 264, 10589-10594.
  90. Moreno, M.L. and M. Landgraf. 1998. Virulence factors and pathogenicity of Vibrio vulnificus strains isolated from seafood. J. Appl. Microbiol. 84,747-751.
  91. Musher, D.M. 1989. Cutaneous manifestations of bacterial sepsis. Hosp. Pract. (Off. Ed). 24, 71-5, 80-2, 92 passim.
  92. Nilsson, WB., R.N. Paranjype, A DePaola, and M.S. Strom. 2003. Sequence polymorphism of the 16S rRNA gene of Vibrio vulnificus is a possible indicator of strain virulence. J. Clin. Microbiol. 41, 442-446.
  93. Nishina, Y, S. Miyoshi, A Nagase, and S. Shinoda. 1992. Significant role of an exocellular protease in utilization of heme by Vibrio vulnificus. Infect. lmmun. 60, 2128-2132.
  94. Okujo, N., T. Akiyama, S. Miyoshi, S. Shinoda, and S. Yamamoto. 1996. Involvement of vulnibactin and exocellular protease in utilization of transferrin- and lactoferrin-bound iron by Vibrio vulnificus. Microbial. Immunol. 40, 595-598.
  95. Okujo, N., M. Saito, S. Yamamoto, T. Yoshida, S. Miyoshi, and S. Shinoda. 1994. Structure of vulnibactin, a new polyamine-containing siderophore from Vibrio vulnificus. Biometals. 7, 109-116.
  96. Oliver, J.D., J.E. Wear, M.B. Thomas, M. Warner, and K Linder. 1986. Production of extracellular enzymes and cytotoxicity by Vibrio vulnificus. Diagn. Microbiol. Infect. Dis. 5, 99-111.
  97. Osaka, K, M. Komatsuzaki, H. Takahashi, S. Sakano, and N. Okabe. 2004. Vibrio vulnificus septicaemia in Japan: an estimated number of infections and physicians' knowledge of the syndrome. Epidemiol. Infect. 132, 993-996.
  98. Paranjpye, RN., J.e. Lara, J.e. Pepe, e.M. Pepe, and M.S. Strom. 1998. The type IV leader peptidase/N-methyltransferase of Vibrio vulnificus controls factors required for adherence to HEp-2 cells and virulence in iron-overloaded mice. Infect. Immun. 66, 5659-5668.
  99. Park, KJ., MJ. Kang, S.H. Kim, H.J. Lee, J.K Lim, S.H. Choi, S.J. Park, and KH. Lee. 2004. Isolation and characterization of rpoS from a pathogenic bacterium, Vibrio vulnificus: role of sigmaS in survival of exponential-phase cells under oxidative stress. J. Bacteriol. 186, 3304-3312.
  100. Patruta, S.I., R. Edlinger, G Sunder-Plassmann, and W.H. Horl. 1998. Neutrophil impairment associated with iron therapy in hemodialysis pateints with functional iron deficiency. J. Am. Soc. Nephrol. 9, 655-663.
  101. Powell, J.L., KA. Strauss, C. Wiley, M. Zhan, and J.G Morris, Jr. 2003. Inflammatory cytokine response to Vibrio vulnificus elicited by peripheral blood mononuclear cells from chronic alcohol users is associated with biomarkers of cellular oxidative stress. Infect. Immun. 71,4212-4216.
  102. Rhee, J.H., Y.R Kim, S.Y. Kim, e.M. Kim, Y.S. Jin, S.E. Lee, and S.S. Chung. 2001. RTX toxin is a key virulence factor in Vibrio vulnificus pathogenesis. Abstr. B-325, p. 113-114. Abstr. Annu. Meet. Am. Soc. Microbial.
  103. Rhee, J., Y. Kim, S. Kim, e. Kim, P. Ryu, H. Choy, and S. Chung. 2002. Vibrio vulnificus Rtx toxin, a newly discovered key virulence factor, causes cytoskeletal rearrangement of host cells. Abstr. B-285, p. 81. Abstr. Annu. Meet. Am. Soc. Microbiol.
  104. Rho, H.W., MJ. Choi, J.N. Lee, J.w. Park, J.S. Kim, B.H. Park, H.S. Sohn, and H.R. Kim. 2002. Cytotoxic mechanism of Vibrio vulnificus cytolysin in CPAE cells. Life Sci. 70, 1923-1934.
  105. Shao, CP and LJ. Hor. 2000. Metalloprotease is not essential for Vibrio vulnificus virulence in mice. Infect. Immun. 68, 3569-3573.
  106. Shao, e.P. and L.I. Hor. 2001. Regulation of metalloprotease gene expression in Vibrio vulnificus by a Vibrio harveyi LuxR homologue. J. Bacteriol. 183, 1369-1375.
  107. Shapiro, R.L., S. Altekruse, L. Hutwagner, R Bishop, R Hammond, S. Wilson, B. Ray, S. Thompson, RV. Tauxe, and P.M. Griffin. 1998. The role of Gulf Coast oysters harvested in warmer months in Vibrio vulnificus infections in the United States, 1988-1996. Vibrio Working Group. J. Infect. Dis. 178, 752-759.
  108. Shinoda, S., M. Kobayashi, H. Yamada, S. Yoshida,M. Ogawa, and Y. Mizuguchi. 1987. Inhibitory effect of capsular antigen of Vibrio vulnificus on bactericidal activity of human serum. Microbiol. Immunol. 31, 393-401.
  109. Shinoda, S., S. Miyoshi, H. Yamanaka, and N. Miyoshi-Nakahara. 1985. Some properties of Vibrio vulnificus hemolysin. Microbiol. Immunol. 29, 583-590.
  110. Simpson, L.M. and J.D. Oliver. 1983. Siderophore production by Vibrio vulnificus. Infect. Immun. 41, 644-649.
  111. Simpson, L.M., V.K White, S.P. Zane, and J.D. Oliver. 1987. Correlation between virulence and colony morphology in Vibrio vulnificus. Infect. Immun. 55, 269-272.
  112. Smith, AB. and RJ. Siebeling. 2003. Identification of genetic loci required for capsular expression in Vibrio vulnificus. Infect. Immun. 71, 1091-1097.
  113. Smith, Ge. and J.R Merkel. 1982. Collagenolytic activity of Vibrio vulnificus: potential contribution to its invasiveness. Infect. Immun. 35, 1155-1156.
  114. Starks, AM., T.R. Schoeb, M.L. Tamplin, S. Parveen, TJ. Doyle, P.E. Bomeisl, GM. Escudero, and PA Gulig. 2000. Pathogenesis of infection by clinical and environmental strains of Vibrio vulnificus in iron dextran-treated mice. Infect. Immun. 68, 5785-5793.
  115. Stelma, GN., Jr., A.L. Reyes, J.T. Peeler, e.H. Johnson, and P.L. Spaulding. 1992. Virulence characteristics of clinical and environmental isolates of Vibrio vulnificus. Appl. Environ. Microbiol. 58, 2776-2782.
  116. Strom, M.S. and RN. Paranjpye. 2000. Epidemiology and pathogenesis of Vibrio vulnificus. Microbes Infect. 2, 177-188.
  117. Tamplin, M.L., J.K Jackson, e. Buchrieser, RL. Murphree, KM. Portier, V Gangar, L.G Miller, and C.w. Kaspar. 1996. Pulsedfield gel electrophoresis and ribotype profiles of clinical and environmental Vibrio vulnificus isolates. Appl. Environ. Microbiol. 62, 3572-3580.
  118. Tison, D.L. and M.T. Kelly. 1986. Virulence of Vibrio vulnificus strains from marine environments. Appl. Environ. Microbiol. 51, 1004-1006.
  119. van Asbeck, B.S., U. Marx, A. Struyvenberg, and J. Verhoef. 1984. Functional defects in phagocytic cells from patients with iron overload. J. Infect. 8, 232-240.
  120. Vollberg, e.M. and J.L. Herrera. 1997. Vibrio vulnificus infection: an important cause of septicemia in patients with cirrhosis. South. Med. J. 90, 1040-1042
  121. Weinberg, E.D. 2000. Microbial pathogens with impaired ability to acquire host iron. Biometals. 13, 85-89.
  122. Wright, Ae. and J.G Morris, JI. 1991. The extracellular cytolysin of Vibrio vulnificus:. inactivation and relationship to virulence in mice. Infect. Immun. 59, 192-197.
  123. Wright, Ae., J.G Morris, Jr., D.R. Maneval, Jr., K Richardson, and J.B. Kaper. 1985. Cloning of the cytotoxin-hemolysin gene of Vibrio vulnificus. Infect. Immun. 50, 922-924.
  124. Wright, A.e., J.L. Powell, J.B. Kaper, and J.G Morris, JI. 2001. Identification of a group I-like capsular polysaccharide operon for Vibrio vulnificus. Infect. Immun. 69,6893-6901.
  125. Wright, A.c., J.L. Powell, M.K. Tanner, L.A Ensor, AB. Karpas, J.G Morris, Jr., and M.B. Sztein. 1999. Differential expression of Vibrio vulnificus capsular polysaccharide. Infect. Immun. 67, 2250-2257.
  126. Wright, AC., L.M. Simpson, and J.D. Oliver. 1981. Role of iron in the pathogenesis of Vibrio vulnificus infections. Infect. Immun. 34, 503-507.
  127. Wright, Ae., L.M. Simpson, J.D. Oliver, and J.G Morris, Jr. 1990. Phenotypic evaluation of acapsular transposon mutants of Vibrio vulniflcus. Infect. Immun. 58, 1769-1773.
  128. Wu, S.I., S.K. La, C.P. Shao, HW. Tsai, and L.I. Hor. 2001. Cloning and characterization of a periplasmic nuclease of Vibrio vulnificus and its role in preventing uptake of foreign DNA. Appl. Environ. Microbiol. 67, 82-88.
  129. Yoshida, S., M. Ogawa, and Y. Mizuguchi. 1985. Relation of capsular materials and colony opacity to virulence of Vibrio vulnificus. Infect. Immun. 47,446-451.
  130. Young, GM., D.H. Schmiel, and VL. Miller. 1999. A new pathway for the secretion of virulence factors by bacteria: the flagellar export apparatus functions as a protein-secretion system. Proc. Natl. Acad. Sci. U. S. A. 96, 6456-6461.
  131. Zuppardo, A.B. and R.I. Siebeling. 1998. An epimerase gene essential for capsule synthesis in Vibrio vulnificus. Infect. Immun. 66, 2601-2606.