Sialic Acid Catabolism Confers a Competitive Advantage to Pathogenic
            <i>Vibrio cholerae</i>
            in the Mouse Intestine

Almagro‐Moreno, Salvador; Boyd, E. Fidelma

doi:10.1128/iai.00279-09

Cited by 168 publications

(198 citation statements)

References 82 publications

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“…The type III secretion systems most frequently found in V. cholerae serogroups non-O1/non-O139 induce severe diarrhea in cholera infection models (29), and this secretion system has been reported in V. cholerae strains that encode and express the O1-antigen (15). Our results are consistent with previous studies that showed VPI-2 to be highly heterogeneous in clinical and environmental strains (15,28).…”

supporting

confidence: 83%

“…That is, the VPI-2 locus in non-O1/O139 strains lack most of the VPI-2 ORFs, including the type 1 restriction modification system and mu-like phage regions (Table S3). Interestingly, the sialidase has been shown to unmask the GM1 gangliosides of human intestinal epithelial cells, thus making them more available to CT (28). However, because many of these strains do not encode CT, the high level of conservation of sialidase among these strains suggests an additional role for sialidase in the life cycle of Vibrio.…”

mentioning

confidence: 99%

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Genomic diversity of 2010 Haitian cholera outbreak strains

Hasan

Choi

Eppinger

et al. 2012

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

173

212

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The millions of deaths from cholera during the past 200 y, coupled with the morbidity and mortality of cholera in Haiti since October 2010, are grim reminders that Vibrio cholerae , the etiologic agent of cholera, remains a scourge. We report the isolation of both V . cholerae O1 and non-O1/O139 early in the Haiti cholera epidemic from samples collected from victims in 18 towns across eight Arrondissements of Haiti. The results showed two distinct populations of V. cholerae coexisted in Haiti early in the epidemic. As non-O1/O139 V . cholerae was the sole pathogen isolated from 21% of the clinical specimens, its role in this epidemic, either alone or in concert with V . cholerae O1, cannot be dismissed. A genomic approach was used to examine similarities and differences among the Haitian V . cholerae O1 and V . cholerae non-O1/O139 strains. A total of 47 V . cholerae O1 and 29 V . cholerae non-O1/O139 isolates from patients and the environment were sequenced. Comparative genome analyses of the 76 genomes and eight reference strains of V . cholerae isolated in concurrent epidemics outside Haiti and 27 V . cholerae genomes available in the public database demonstrated substantial diversity of V. cholerae and ongoing flux within its genome.

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supporting

confidence: 83%

mentioning

confidence: 99%

Genomic diversity of 2010 Haitian cholera outbreak strains

Hasan

Choi

Eppinger

et al. 2012

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

173

212

View full text Add to dashboard Cite

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“…The ripR gene (the gene encoding for ribose phosphate isomerase regulator) in this cluster has been predicted to encode a repressive regulator (11). The V. cholerae (O1 biovar El Tor strain N16961) ripR protein shares 79% identity with V. vulnificus NanR (SI Appendix, Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Escherichia coli, Vibrio cholerae, Vibrio vulnificus, and Staphylococcus aureus can grow by using Neu5Ac as a sole carbon source (10)(11)(12)(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).…”

mentioning

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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“…Sialic acid is ubiquitously found in mucus-rich areas of gut and lung and it can be utilized as a sole carbon and energy source by pathogenic and commensal bacteria (Severi et al, 2007;Almagro-Moreno & Boyd, 2009). A cluster of genes involved in scavenging, transport and catabolism of sialic acid have been identified in V. cholerae; one of the genes of this cluster encodes neuraminidase (NanH), which plays an important role in making sialic acid available to bacteria as a carbon source and in binding of cholera toxin to sialogangliosides (Galen et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

Functional characterization of VC1929 of Vibrio cholerae El Tor: role in mannose-sensitive haemagglutination, virulence and utilization of sialic acid

et al. 2011

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The nonadhesive mutant CD11 of Vibrio cholerae El Tor, defective in expression of mannosesensitive haemagglutinin, lacks a protein when compared with its parent strain. Determination of the amino acid sequence revealed the identity of the protein as the product of VC1929, which is annotated to encode a protein, DctP, involved in the transport of C 4 -dicarboxylates. We cloned the dctP gene in pUC19 vector and expressed it in mutant CD11. Expression of DctP in the resulting complemented strain restored virulence, adhesive and colonizing capabilities, mannosesensitive haemagglutination (MSHA) and ability to grow in medium containing sialic acid as a sole carbon source. The mutation in CD11 was caused by insertion of an adenine nucleotide in the reading frame of dctP. Recombinant purified DctP protein showed MSHA of human red blood cells, and protected rabbits against infection by V. cholerae. The protein was localized in membrane and cell wall fractions. The mutant, recombinant CD11 expressing DctP and parent strains were grown in M9 minimal medium in the presence of various carbohydrates (glucose, malate, fumarate, succinate or N-acetylneuraminic acid). The mutant was unable to grow in minimal medium containing N-acetylneuraminic acid (sialic acid) as the sole carbon source whereas the recombinant and parent strains utilized all the sugars tested. It is concluded that DctP is a mannose-sensitive haemagglutinin and a virulence factor and is involved in the utilization of sialic acid.

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Sialic Acid Catabolism Confers a Competitive Advantage to Pathogenic Vibrio cholerae in the Mouse Intestine

Cited by 168 publications

References 82 publications

Genomic diversity of 2010 Haitian cholera outbreak strains

Genomic diversity of 2010 Haitian cholera outbreak strains

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

Functional characterization of VC1929 of Vibrio cholerae El Tor: role in mannose-sensitive haemagglutination, virulence and utilization of sialic acid

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