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Deciphering the possible role of ctxb7 allele on higher production of cholera toxin by haitian variant vibrio cholerae o1

Naha, A and Mandal, RS and Samanta, P and Saha, RN and Shaw, S and Ghosh, A and Chatterjee, NS and Dutta, P and Okamoto, K and Dutta, S and Mukhopadhyayid, AK (2020) Deciphering the possible role of ctxb7 allele on higher production of cholera toxin by haitian variant vibrio cholerae o1. In: PLoS Neglected Tropical Diseases, 14 (4). pp. 1-24.

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Official URL: https://doi.org/10.1371/journal.pntd.0008128


Cholera continues to be an important public health concern in developing countries where proper hygiene and sanitation are compromised. This severe diarrheal disease is caused by the Gram-negative pathogen Vibrio cholerae belonging to serogroups O1 and O139. Cholera toxin (CT) is the prime virulence factor and is directly responsible for the disease mani-festation. The ctxB gene encodes cholera toxin B subunit (CTB) whereas the A subunit (CTA) is the product of ctxA gene. Enzymatic action of CT depends on binding of B penta-mers to the lipid-based receptor ganglioside GM1. In recent years, emergence of V. cholerae Haitian variant strains with ctxB7 allele and their rapid spread throughout the globe has been linked to various cholera outbreaks in Africa and Asia. These strains produce classical type (WT) CTB except for an additional mutation in the signal sequence region where an asparagine (N) residue replaces a histidine (H) at the 20th amino acid position (H20N) of CTB precursor (pre-CTB). Here we report that Haitian variant V. cholerae O1 strains isolated in Kolkata produced higher amount of CT compared to contemporary O1 El Tor variant strains under in vitro virulence inducing conditions. We observed that the ctxB7 allele, itself plays a pivotal role in higher CT production. Based on our in silico analysis, we hypothesized that higher accumulation of toxin subunits from ctxB7 allele might be attributed to the structural alteration at the CTB signal peptide region of pre-H20N CTB. Overall, this study provides plausible explanation regarding the hypertoxigenic phenotype of the Haitian variant strains which have spread globally, possibly through positive selection for increased patho-genic traits. © 2020 Naha et al.

Item Type: Journal Article
Publication: PLoS Neglected Tropical Diseases
Publisher: Public Library of Science
Additional Information: The copyright for this article belongs to the Authors.
Keywords: arabinose; cholera toxin; restriction endonuclease; RNA 16S; bacterial RNA; cholera toxin; virulence factor, allele; Article; bacterial gene; bacterial virulence; bacterium culture; bioinformatics; controlled study; enzyme linked immunosorbent assay; Escherichia coli; gene expression; gene function; gene identification; gene mutation; Haitian; molecular cloning; molecular model; nonhuman; nucleotide sequence; phenotype; phenotypic variation; plasmid; protein structure; reverse transcription polymerase chain reaction; RNA isolation; toxin synthesis; upregulation; Vibrio cholerae O1; Western blotting; bacterial gene; bacterium identification; chemistry; cholera; epidemic; gene expression regulation; genetics; Haiti; human; metabolism; microbiology; serotype; Vibrio cholerae O1; virulence, Alleles; Bacterial Typing Techniques; Cholera; Cholera Toxin; Disease Outbreaks; Escherichia coli; Gene Expression Regulation, Bacterial; Genes, Bacterial; Haiti; Humans; RNA, Bacterial; Serogroup; Vibrio cholerae O1; Virulence; Virulence Factors
Department/Centre: Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited: 24 Jan 2023 05:12
Last Modified: 24 Jan 2023 05:12
URI: https://eprints.iisc.ac.in/id/eprint/79382

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