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

Arindam Naha, Rahul Shubhra Mandal, Prosenjit Samanta, Rudra Narayan Saha, Sreeja Shaw, Amit Ghosh, Nabendu Sekhar Chatterjee, Pujarini Dutta, Keinosuke Okamoto, Shanta Dutta, Asish Kumar Mukhopadhyayid

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article numbere0008128
Pages (from-to)1-24
Number of pages24
JournalPLoS neglected tropical diseases
Volume14
Issue number4
DOIs
Publication statusPublished - Apr 2020

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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    Naha, A., Mandal, R. S., Samanta, P., Saha, R. N., Shaw, S., Ghosh, A., Chatterjee, N. S., Dutta, P., Okamoto, K., Dutta, S., & Mukhopadhyayid, A. K. (2020). Deciphering the possible role of ctxb7 allele on higher production of cholera toxin by haitian variant vibrio cholerae o1. PLoS neglected tropical diseases, 14(4), 1-24. [e0008128]. https://doi.org/10.1371/journal.pntd.0008128