Characterization and Pathogenic Significance of
            <i>Vibrio vulnificus</i>
            Antigens Preferentially Expressed in Septicemic Patients

Kim, Young Ran; Lee, Shee Eun; Kim, Choon Mee; Kim, Soo Young; Shin, Eun Ju; Shin, Dong-Hyeon; Chung, Sun Sik; Choy, Hyon E.; Progulske‐Fox, Ann; Hillman, Jeffrey D.; Handfield, Martin; Rhee, Joon Haeng

doi:10.1128/iai.71.10.5461-5471.2003

Cited by 258 publications

(226 citation statements)

References 67 publications

(63 reference statements)

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“…Toxins of the MARTX family are very large composite toxins. The 5,206-amino acid MARTX Vv toxin as found in the two sequenced strains of V. vulnificus, Korean isolate CMCP6 and Taiwanese isolate YJ016 (9,10), are 99% identical. Similar to all MARTX toxins, the majority of MARTX Vv is comprised of conserved repeat regions at the N and C termini that are proposed to form a pore in the eukaryotic cell plasma membrane for translocation of the central portion of the secreted toxin to the cytosol (11).…”

mentioning

confidence: 81%

Vibrio vulnificus rtxA1 gene recombination generates toxin variants with altered potency during intestinal infection

Kwak

Jeong

Satchell

2011

Proc. Natl. Acad. Sci. U.S.A.

143

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Vibrio vulnificus is a food-borne bacterial pathogen associated with 1% of all food-related deaths, predominantly because of consumption of contaminated seafood. The ability of V. vulnificus to cause disease is linked to the production of a large cytotoxin called the "multifunctional-autoprocessing RTX" (MARTX Vv ) toxin, a factor shown here to be an important virulence factor by the intragastric route of infection in mice. In this study, we examined genetic variation of the rtxA1 gene that encodes MARTX Vv in 40 V. vulnificus Biotype 1 strains and found four distinct variants of rtxA1 that encode toxins with different arrangements of effector domains. We provide evidence that these variants arose by recombination either with rtxA genes carried on plasmids or with the rtxA gene of Vibrio anguillarum. Contrary to expected results, the most common rtxA1 gene variant in clinical-type V. vulnificus encodes a toxin with reduced potency and is distinct from the toxin produced by strains isolated from market oysters. These results indicate that an important virulence factor of V. vulnificus is undergoing significant genetic rearrangement and may be subject to selection for reduced virulence in the environment. This finding would imply further that in the future on-going genetic variation of the MARTX Vv toxins could result in the emergence of novel strains with altered virulence in humans.phylogeny | RTX | oyster T he gram-negative bacterial pathogen Vibrio vulnificus inhabits coastal waters including the US Gulf Coast. The pathogen causes gastroenteritis, primary septicemia, and necrotizing fasciitis and can be difficult to treat. The bacteria are particularly rapid growers in vivo and are highly invasive; thus death can occur as quickly as 24-48 h after ingestion (1, 2). In the United States from 1998-2008, 985 cases of V. vulnificus infection resulting in 91 deaths were reported to the Centers for Disease Control. Of these cases, 60% were caused by food-borne illness, particularly associated with the consumption of raw seafood (3). In fact, V. vulnificus accounts for 1% of all food-related deaths in the United States (4). Numerous studies recently have described a V. vulnificus multifunctional-autoprocessing RTX toxin (MARTX Vv ) as having a major impact on virulence in mice (5-8). Toxins of the MARTX family are very large composite toxins. The 5,206-amino acid MARTX Vv toxin as found in the two sequenced strains of V. vulnificus, Korean isolate CMCP6 and Taiwanese isolate YJ016 (9, 10), are 99% identical. Similar to all MARTX toxins, the majority of MARTX Vv is comprised of conserved repeat regions at the N and C termini that are proposed to form a pore in the eukaryotic cell plasma membrane for translocation of the central portion of the secreted toxin to the cytosol (11). The central region includes a conserved cysteine protease domain (CPD) that is required for inositol hexakisphosphate-induced autoprocessing. After translocation, autoprocessing at leucine residues in unstructured regions between the effector do...

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mentioning

confidence: 81%

Vibrio vulnificus rtxA1 gene recombination generates toxin variants with altered potency during intestinal infection

Kwak

Jeong

Satchell

2011

Proc. Natl. Acad. Sci. U.S.A.

143

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“…Among these technologies, IVIAT is significantly superior to other reported in vivo expression technologies because it avoids the use of animal model (Handfield et al 2005). It has been applied in several important pathogenic bacteria for the identification of new virulent factors (Deb et al 2002;Kim et al 2003;Fernández et al 2004;Akhtar et al 2006;Lee et al 2007).…”

Section: Introductionmentioning

confidence: 99%

“…To remove the in vitro-derived V. anguillarum and E. coli antigens, whole cells, cell extracts and heat-denatured cell extracts of both strains were prepared and used to absorb the convalescent sera and the control sera as described previously (Kim et al 2003). ELISA was performed to determine the antibody titre and to check the efficacy of each adsorption.…”

Section: Preparation Of Convalescent-phase Sera From Fishmentioning

confidence: 99%

Screening of genes expressed in vivo after infection by Vibrio anguillarum M3

Zou

Hao

et al. 2010

Letters in Applied Microbiology

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Aims: Genes uniquely expressed in vivo may contribute to the overall pathogenicity of an organism and are likely to serve as potential targets for the development of new vaccine. This study aims to screen the genes expressed in vivo after Vibrio anguillarum infection by in vivo‐induced antigen technology (IVIAT). Methods and Results: The convalescent‐phase sera were obtained from turbot (Scophthalmus maximus) survived after infection by the virulent V. anguillarum M3. The pooled sera were thoroughly adsorbed with M3 cells and Escherichia coli BL21 (DE3) cells. A genomic expression library of M3 was constructed and screened for the identification of immunogenic proteins by colony immunoblot analysis with the adsorbed sera. After three rounds of screening, 19 putative in vivo‐induced (ivi) genes were obtained. These ivi genes were catalogued into four functional groups: regulator/signalling, metabolism, biological process and hypothetical proteins. Three ivi genes were insertion‐mutated, and the growth and 50% lethal dose (LD50) of these mutants were evaluated. Conclusions: The identification of ivi genes in V. anguillarum M3 sheds light on understanding the bacterial pathogenesis and provides novel targets for the development of new vaccines and diagnostic reagents. Significance and Impact of the Study: To the best of our knowledge, this is the first report describing in vivo‐expressed genes of V. anguillarum using IVIAT. The screened ivi genes in this study could be new virulent factors and targets for the development of vaccine, which may have implications for the development of diagnostic regents.

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“…6B), and G6PD (data not shown), revealed nearly identical patterns for the four isolates. Further, we analyzed the corresponding SI genes of the recently available genome sequence of a Korean isolate (AE016795, AE016796; Kim et al 2003). In V. vulnificus CMCP6, the SI spans nearly 151 kbp and the region harbors 211 attC sites.…”

Section: Genome Research 2583mentioning

confidence: 99%

Comparative Genome Analysis of Vibrio vulnificus, a Marine Pathogen

et al. 2003

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The halophile Vibrio vulnificus is an etiologic agent of human mortality from seafood-borne infections. We applied whole-genome sequencing and comparative analysis to investigate the evolution of this pathogen. The genome of biotype 1 strain, V. vulnificus YJ016, was sequenced and includes two chromosomes of estimated 3377 kbp and 1857 kbp in size, and a plasmid of 48,508 bp. A super-integron (SI) was identified, and the SI region spans 139 kbp and contains 188 gene cassettes. In contrast to non-SI sequences, the captured gene cassettes are unique for any given Vibrio species and are highly variable among V. vulnificus strains. Multiple rearrangements were found when comparing the 5.3-Mbp V. vulnificus YJ016 genome and the 4.0-Mbp V. cholerae El Tor N16961 genome. The organization of gene clusters of capsular polysaccharide, iron metabolism, and RTX toxin showed distinct genetic features of V. vulnificus and V. cholerae. The content of the V. vulnificus genome contained gene duplications and evidence of horizontal transfer, allowing for genetic diversity and function in the marine environment. The genomic information obtained in this study can be applied to monitoring vibrio infections and identifying virulence genes in V. vulnificus.[Supplemental material is available online at www.genome.org and at http://genome.nhri.org.tw/vv/. The nucleotide sequence data from this study have been submitted to DDBJ/EMBL/GenBank under accession nos. BA000037, BA000038, and AP005352.]Vibrio vulnificus is an etiologic agent for severe human infection acquired through wounds or contaminated seafood. This organism is divided into three biotypes according to their different biochemical and biological properties (Linkous and Oliver 1999). Among them the biotype 1 strains are most frequently isolated from the clinical specimens. Opportunistic infection in susceptible individuals typically causes mortality within 24 to 48 h of the exposure. The bacterium is halophilic, and it is abundantly present in estuarine ecosystems throughout the world. Isolated incidents of V. vulnificus infection have been reported in the U.S.A., Europe, Korea, Taiwan (Park et al. 1991;Chuang et al. 1992;Dalsgaard et al. 1996;Hlady and Klontz 1996), and many other countries. According to CDC statistics, V. vulnificus is a major bacterial cause of mortality associated with food-borne diseases, and it results in the highest death rate of any causative agent (Todd 1989).V. vulnificus belongs to the ␥-group of Proteobacteria, and it shares morphological and biochemical characteristics with other human vibrio pathogens, including Vibrio cholerae and Vibrio parahaemolyticus. Bacteria of the Vibrionaceae family, which show a comma-shape microscopic appearance and a polar flagellum appendage, are mostly aquatic inhabitants that require NaCl for optimal growth. On the basis of clinical and epidemiology studies, diseases associated with V. vulnificus infection have been found to present in two patterns (Blake et al. 1979). In one, primary septicemia occurred in individ...

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Characterization and Pathogenic Significance of Vibrio vulnificus Antigens Preferentially Expressed in Septicemic Patients

Cited by 258 publications

References 67 publications

Vibrio vulnificus rtxA1 gene recombination generates toxin variants with altered potency during intestinal infection

Vibrio vulnificus rtxA1 gene recombination generates toxin variants with altered potency during intestinal infection

Screening of genes expressed in vivo after infection by Vibrio anguillarum M3

Comparative Genome Analysis of Vibrio vulnificus, a Marine Pathogen

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