Role of the Enterotoxic Hemolysin in Pathogenicity of Vibrio mimicus

Li, Tao; Kobayashi, Akito; Takata, Nobuo; Yoshimura, Tomonaga; Maehara, Yoko; Tsuchiya, Tomofusa; Miyoshi, Shin Ichi

doi:10.1248/jhs.54.686

Cited by 6 publications

(6 citation statements)

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“…Previous studies showed that the T3SSs of V. parahaemolyticus and V. cholerae contribute to their pathogenicity for humans [ 14 , 17 , 20 , 22 - 24 ]. In V. mimicus , a bacterium which is known to be a causative agent of gastroenteritis in humans, the hemolysin was previously reported as a major virulence factor [ 26 ]. To assess the function of T3SS of V. mimicus in pathogenicity in our study, we evaluated the cytotoxicity of V. mimicus for Caco-2 cells because V. parahaemolyticus had a T3SS2-dependent cytotoxic effect on Caco-2 cells [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

“…Although we could not detect statistically significant differences between T3SS-deficient mutants and parental strains, there was a tendency for the cytotoxicity of T3SS-deficient mutants to diminish than that of the parental mutants. A previous report showed that the deletion of the hemolysin gene in V. mimicus significantly reduced fluid accumulation in rabbit ileal loop tests, but the mutant partially retained this action, which suggests that, besides the hemolysin, V. mimicus may contain an additional virulence determinant(s) [ 26 ]. It is therefore possible that T3SS is a candidate for the previously unidentified virulence determinant in pathogenic V. mimicus strains for humans.…”

Section: Discussionmentioning

confidence: 99%

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Presence of genes for type III secretion system 2 in Vibrio mimicus strains

et al. 2010

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Background Vibrios, which include more than 100 species, are ubiquitous in marine and estuarine environments, and several of them e.g. Vibrio cholerae , V. parahaemolyticus , V. vulnificus and V. mimicus , are pathogens for humans. Pathogenic V. parahaemolyticus strains possess two sets of genes for type III secretion system (T3SS), T3SS1 and T3SS2. The latter are critical for virulence of the organism and be classified into two distinct phylogroups, T3SS2α and T3SS2β, which are reportedly also found in pathogenic V. cholerae non-O1/non-O139 serogroup strains. However, whether T3SS2-related genes are present in other Vibrio species remains unclear. Results We therefore examined the distribution of the genes for T3SS2 in vibrios other than V. parahaemolyticus by using a PCR assay targeting both T3SS2α and T3SS2β genes. Among the 32 Vibrio species tested in our study, several T3SS2-related genes were detected in three species, V. cholerae , V. mimicus and V. hollisae , and most of the essential genes for type III secretion were present in T3SS2-positive V. cholerae and V. mimicus strains. Moreover, both V. mimicus strains possessing T3SS2α and T3SS2β were identified. The gene organization of the T3SS2 gene clusters in V. mimicus strains was fundamentally similar to that of V. parahaemolyticus and V. cholerae in both T3SS2α- and T3SS2β-possessing strains. Conclusions This study is the first reported evidence of the presence of T3SS2 gene clusters in V. mimicus strains. This finding thus provides a new insight into the pathogenicity of the V. mimicus species.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Presence of genes for type III secretion system 2 in Vibrio mimicus strains

et al. 2010

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“…Although several enterotoxic factors, including a cholera toxin‐like enterotoxin, have been isolated [4,5], a heat‐labile hemolysin, designated V. mimicus hemolysin (VMH) [6], may be the most important virulence factor of the pathogen. Purified VMH can induce fluid accumulation when injected into a ligated ileal loop [6,7] and specific antibody against VMH significantly inhibits fluid accumulation [6,8]. A VMH‐negative mutant showed reduced ability to cause fluid accumulation [8].…”

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confidence: 99%

“…Purified VMH can induce fluid accumulation when injected into a ligated ileal loop [6,7] and specific antibody against VMH significantly inhibits fluid accumulation [6,8]. A VMH‐negative mutant showed reduced ability to cause fluid accumulation [8]. Moreover, the gene encoding VMH is present in all strains from various clinical and environmental sources [9].…”

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confidence: 99%

Modulation of Vibrio mimicus hemolysin through limited proteolysis by an endogenous metalloprotease

et al. 2009

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Vibrio mimicus is a causative agent of human gastroenteritis and food poisoning, and this species produces an enterotoxic hemolysin (V. mimicus hemolysin) as a virulence determinant. Vibrio mimicus hemolysin is secreted as an 80 kDa precursor, which is later converted to the 66 kDa mature toxin through removal of an N‐terminal propeptide via cleavage of the Arg151–Ser152 bond. In this article, we investigate the role of the endogenous metalloprotease (V. mimicus protease) in the maturation of V. mimicus hemolysin. In vitro experiments using purified proteins showed that, although it activated the precursor at the early stage via cleavage of the Asn157–Val158 bond, V. mimicus protease finally converted the activated and physiologically maturated toxin to a 51 kDa protein through removal of the C‐terminal polypeptide. This 51 kDa derivative was unable to lyse erythrocytes because of its inability to bind to the erythrocyte membrane. Vibrio mimicus protease‐negative strains were found to produce high levels of V. mimicus hemolysin at the logarithmic phase of bacterial growth and maintained high hemolytic activity even at the stationary phase. These findings indicate that, although it is not directly related to toxin maturation in vivo, V. mimicus protease can modulate the activity of V. mimicus hemolysin and/or its precursor through limited proteolysis.

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“…Therefore, although the hemolytic activity of VMH is apparently reduced, the enterotoxic activity may be not eliminated by incubation with HD-5. VMH has been documented to be a determinant of the putative virulence of diarrheal diseases Miyoshi t al., 1997;Li et al, 2008 . The findings shown herein may support the FIG.…”

Section: Figmentioning

confidence: 99%

Defensive Effects of Human Intestinal Antimicrobial Peptides against Infectious Diseases Caused by Vibrio mimicus and V. vulnificus

et al. 2014

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Of human pathogenic Vibrio species, V. mimicus causes gastroenteritis whereas V. vulnificus causes fatal septicemia after consumption of contaminated seafood. These two pathogens produce hemolytic toxins termed V. mimicus hemolysin VMH and V. vulnificus hemolysin VVH , respectively. These toxins elicit the cytolysis of various eukaryotic cells, as well as erythrocytes. The human intestine secretes cationic antimicrobial peptides AMPs to prevent infectious diseases. Paneth cells in the small intestine secrete -defensin 5 HD-5 and epithelial cells in the large intestine produce LL-37. In the present study, we examined the bactericidal activities of AMPs against V. mimicus and V. vulnificus. Although HD-5 showed no bactericidal activity, LL-37 revealed significant activity against both Vibrio species, suggesting that neither V. mimicus nor V. vulnificus can multiply in the large intestine. We also tested whether AMPs had the ability to inactivate the hemolytic toxins. Only HD-5 was found to inactivate VMH, but not VVH, in a dose-dependent manner through the direct binding to VMH. Therefore, it is considered that V. mimicus cannot penetrate the small intestinal epithelium because the cytolytic action of VMH is inactivated by HD-5.

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Role of the Enterotoxic Hemolysin in Pathogenicity of Vibrio mimicus

Cited by 6 publications

References 22 publications

Presence of genes for type III secretion system 2 in Vibrio mimicus strains

Presence of genes for type III secretion system 2 in Vibrio mimicus strains

Modulation of Vibrio mimicus hemolysin through limited proteolysis by an endogenous metalloprotease

Defensive Effects of Human Intestinal Antimicrobial Peptides against Infectious Diseases Caused by Vibrio mimicus and V. vulnificus

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