Characterization of a novel Vibrio pathogenicity island (VPI-2) encoding neuraminidase (nanH) among toxigenic Vibrio cholerae isolates

Jermyn, William S.; Boyd, E. Fidelma

doi:10.1099/00221287-148-11-3681

Cited by 161 publications

(153 citation statements)

References 41 publications

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“…VPI-2. VPI-2 is a 57.3-kb gene cluster that encodes genes for neuraminidase and sialic acid metabolism and has characteristic features of a pathogenicity island (28). The genome of V. mimicus MB451 encodes a ca.…”

Section: Resultsmentioning

confidence: 99%

Comparative genomics of clinical and environmental Vibrio mimicus

Hasan

Grim

Haley

et al. 2010

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

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Whether Vibrio mimicus is a variant of Vibrio cholerae or a separate species has been the subject of taxonomic controversy. A genomic analysis was undertaken to resolve the issue. The genomes of V. mimicus MB451, a clinical isolate, and VM223, an environmental isolate, comprise ca. 4,347,971 and 4,313,453 bp and encode 3,802 and 3,290 ORFs, respectively. As in other vibrios, chromosome I (C-I) predominantly contains genes necessary for growth and viability, whereas chromosome II (C-II) bears genes for adaptation to environmental change. C-I harbors many virulence genes, including some not previously reported in V. mimicus, such as mannose-sensitive hemagglutinin (MSHA), and enterotoxigenic hemolysin (HlyA); C-II encodes a variant of Vibrio pathogenicity island 2 (VPI-2), and Vibrio seventh pandemic island II (VSP-II) cluster of genes. Extensive genomic rearrangement in C-II indicates it is a hot spot for evolution and genesis of speciation for the genus Vibrio. The number of virulence regions discovered in this study (VSP-II, MSHA, HlyA, type IV pilin, PilE, and integron integrase, IntI4) with no notable difference in potential virulence genes between clinical and environmental strains suggests these genes also may play a role in the environment and that pathogenic strains may arise in the environment. Significant genome synteny with prototypic pre-seventh pandemic strains of V. cholerae was observed, and the results of phylogenetic analysis support the hypothesis that, in the course of evolution, V. mimicus and V. cholerae diverged from a common ancestor with a prototypic sixth pandemic genomic backbone.A Gram-negative gamma Proteobacterium, Vibrio mimicus is closely related to Vibrio cholerae. It was first described as a biochemically atypical Vibrio cholerae (1). However, it is phenotypically and genotypically distinct from V. cholerae and can be differentiated from V. cholerae by 12 specific biochemical reactions, including sucrose fermentation, Voges-Proskauer reaction (acetoin production from glucose), lipase production, sodium tartrate fermentation, and polymyxin sensitivity. showed mean pairwise divergence from V. cholerae to be ≈10%, equivalent to the divergence of Salmonella enterica LT2 from Escherichia coli K-12 (2, 3).The natural habitat of V. mimicus is similar to that of V. cholerae, i.e., the aquatic ecosystem, including seawater, freshwater, and brackish water, where it has been found both as a free-living bacterium and in association with zooplankton, crustaceans, filter-feeding mollusks, turtle eggs, and fish. Infections in humans occur from consumption or exposure to these sources (4-9). V. mimicus human gastroenteritis is characterized by diarrhea, nausea, vomiting, abdominal cramps, and fever. However, unlike V. cholerae, V. mimicus has not been associated with epidemics of cholera-like diarrhea, probably because most isolates of V. mimicus do not produce cholera toxin (CT). In fact, Chowdhury et al. (5) reported that fewer than 10% of clinical isolates and fewer than 1% of environmental st...

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Section: Resultsmentioning

confidence: 99%

Comparative genomics of clinical and environmental Vibrio mimicus

Hasan

Grim

Haley

et al. 2010

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

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“…Vibrio pathogenicity island 2, a 57-kb integrative element found exclusively in pathogenic strains of V. cholerae, contains a nan-nag operon that encodes a cluster of genes involved with the transport and catabolism of sialic acid (30). The ripR gene (the gene encoding for ribose phosphate isomerase regulator) in this cluster has been predicted to encode a repressive regulator (11).…”

Section: Discussionmentioning

confidence: 99%

Structural insights into the regulation of sialic acid catabolism by the Vibrio vulnificus transcriptional repressor NanR

Hwang

Kim

Jang

et al. 2013

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

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Pathogenic and commensal bacteria that experience limited nutrient availability in their host have evolved sophisticated systems to catabolize the mucin sugar N-acetylneuraminic acid, thereby facilitating their survival and colonization. The correct function of the associated catabolic machinery is particularly crucial for the pathogenesis of enteropathogenic bacteria during infection, although the molecular mechanisms involved with the regulation of the catabolic machinery are unknown. This study reports the complex structure of NanR, a repressor of the N-acetylneuraminate (nan) genes responsible for N-acetylneuraminic acid catabolism, and its regulatory ligand, N-acetylmannosamine 6-phosphate (ManNAc-6P), in the human pathogenic bacterium Vibrio vulnificus. Structural studies combined with electron microscopic, biochemical, and in vivo analysis demonstrated that NanR forms a dimer in which the two monomers create an arched tunnel-like DNA-binding space, which contains positively charged residues that interact with the nan promoter. The interaction between the NanR dimer and DNA is alleviated by the ManNAc-6P-mediated relocation of residues in the ligand-binding domain of NanR, which subsequently relieves the repressive effect of NanR and induces the transcription of the nan genes. Survival studies in which mice were challenged with a ManNAc-6P-binding-defective mutant strain of V. vulnificus demonstrated that this relocation of NanR residues is critical for V. vulnificus pathogenesis. In summary, this study presents a model of the mechanism that regulates sialic acid catabolism via NanR in V. vulnificus.nan gene repressor | mucin sugar utilization P athogenic bacteria that colonize the host gut are exposed to an adverse environment and competitors (1, 2). These bacteria overcome the limited availability of nutrients in the gut (3) by using alternative carbon sources (4). The mammalian intestinal tract is protected by a mucus layer, which contains heavily glycosylated mucin proteins that comprise up to 85% carbohydrate (5, 6). Sialic acids, which can be used as an energy source by a variety of microbial pathogens and commensals, are found at the distal ends of the mucin carbohydrate chains (7,8). Because the most abundant sialic acid is N-acetylneuraminic acid (Neu5Ac) (7-9), intestinal commensal and pathogenic bacteria have most likely evolved elaborate systems for the catabolic utilization of this substrate.Escherichia coli, Vibrio cholerae, Vibrio vulnificus, and Staphylococcus aureus can grow by using Neu5Ac as a sole carbon source (10-13), and the N-acetylneuraminate (nan) genes responsible for Neu5Ac utilization are up-regulated during their growth on mucus or in the mammalian intestine (3,14). The colonization and pathogenic activities of these bacteria are affected severely by mutations in the nan genes (3, 12, 15). This phenotype suggests that the correct expression and function of the proteins responsible for Neu5Ac catabolism are essential for the growth and survival of enteric bacteria, although onl...

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“…The nanA gene is carried on a pathogenicity island (VPI-2) present in toxigenic strains of V. cholerae (20,21), which also encodes a secreted sialidase, that presumably releases the substrate (the common sialic acid N-acetylneuraminic acid) for use by the cell, while at the same time revealing binding sites for the cholera toxin (22). How sialic acid is taken into the cell has not been formally demonstrated, but it is likely to be through a TRAP transporter (VC1777-1779) encoded in the VPI-2, which is orthologous to HiSiaPQM (15, 19 -21, 23, 24).…”

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confidence: 99%

The Membrane Proteins SiaQ and SiaM Form an Essential Stoichiometric Complex in the Sialic Acid Tripartite ATP-independent Periplasmic (TRAP) Transporter SiaPQM (VC1777–1779) from Vibrio cholerae

Mulligan

Leech

Kelly

et al. 2012

Journal of Biological Chemistry

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Background: Vibrio cholerae has a need for sialic acid transport and catabolism for colonization. Results: The VC1777-1779 genes encode a functional tripartite ATP-independent periplasmic (TRAP) transporter for sialic acid in which the membrane subunits form a tight complex. Conclusion: Vibrio cholerae encodes a functional sialic acid TRAP transporter. Significance: This study reveals the route of sialic acid acquisition by an important human pathogen.

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Characterization of a novel Vibrio pathogenicity island (VPI-2) encoding neuraminidase (nanH) among toxigenic Vibrio cholerae isolates

Cited by 161 publications

References 41 publications

Comparative genomics of clinical and environmental Vibrio mimicus

Comparative genomics of clinical and environmental Vibrio mimicus

Structural insights into the regulation of sialic acid catabolism by the Vibrio vulnificus transcriptional repressor NanR

The Membrane Proteins SiaQ and SiaM Form an Essential Stoichiometric Complex in the Sialic Acid Tripartite ATP-independent Periplasmic (TRAP) Transporter SiaPQM (VC1777–1779) from Vibrio cholerae

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