Comparative Genome Analysis of Vibrio vulnificus, a Marine Pathogen

143

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...

mentioning

confidence: 82%

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

Kwak

Jeong

Satchell

2011

143

“…Recently, the sequence of the V. vulnificus RTX toxin (VvRtxA) was reported (14). The deduced primary amino acid sequences of VcRtxA and VvRtxA were compared and revealed that the two toxins are Ϸ80-90% identical throughout most regions of the toxins.…”

Section: Cholerae and Vibrio Vulnificus Rtx Toxins Have Unique Dommentioning

confidence: 99%

Identification of a domain within the multifunctional Vibrio cholerae RTX toxin that covalently cross-links actin

Sheahan

Cordero

Satchell

2004

124

142

The Gram-negative pathogen Vibrio cholerae causes diarrheal disease through the export of enterotoxins. The V. cholerae RTX toxin was previously identified and characterized by its ability to round human laryngeal epithelial (HEp-2) cells. Further investigation determined that cell rounding is caused by the depolymerization of actin stress fibers, through the unique mechanism of covalent actin cross-linking. In this study, we identify a domain within the full-length RTX toxin that is capable of mediating the cross-linking reaction when transiently expressed within eukaryotic cells. A structure͞function analysis of the actin cross-linking domain (ACD) reveals that a 412-aa, or a 47.8-kDa, region is essential for cross-linking activity. When this domain is deleted from the full-length toxin gene, actin cross-linking, but not cell rounding, is eliminated, indicating that this toxin carries multiple dissociable activities. The ACD shares 59% amino acid identity with a hypothetical protein from V. cholerae, VC1416, and transient expression of the C-terminal domain of VC1416 also results in actin crosslinking in eukaryotic cells. The presence of this second ACD linked to an Rhs-like element suggests that V. cholerae acquired the domain by horizontal gene transfer and the ACD was inserted into the RTX toxin by gene duplication through the evolution of V. cholerae.Vibrio vulnificus ͉ VgrG ͉ covalent actin cross-linking

“…The Vibrionaceae comprise several dozen species that are often found associated with animal tissue (3). Among the small number of pathogenic Vibrio species that cause human diseases are Vibrio cholerae, Vibrio parahaemolyticus, and Vibrio vulnificus, the only members of the Vibrionaceae that have had their genome sequences reported (4)(5)(6). To date, no representative of the much more numerous benign and beneficial Vibrionaceae has been examined at the genome level.…”

mentioning

confidence: 99%

Complete genome sequence of Vibrio fischeri : A symbiotic bacterium with pathogenic congeners

Ruby

Urbanowski

Campbell

et al. 2005

334

238

Vibrio fischeri belongs to the Vibrionaceae, a large family of marine ␥-proteobacteria that includes several dozen species known to engage in a diversity of beneficial or pathogenic interactions with animal tissue. Among the small number of pathogenic Vibrio species that cause human diseases are Vibrio cholerae, Vibrio parahaemolyticus, and Vibrio vulnificus, the only members of the Vibrionaceae that have had their genome sequences reported. Nonpathogenic members of the genus Vibrio, including a number of beneficial symbionts, make up the majority of the Vibrionaceae, but none of these species has been similarly examined. Here we report the genome sequence of V. fischeri ES114, which enters into a mutualistic symbiosis in the light organ of the bobtail squid, Euprymna scolopes. Analysis of this sequence has revealed surprising parallels with V. cholerae and other pathogens.genomics ͉ pili ͉ symbiosis ͉ toxins ͉ toxin-coregulated pilus