Identification of a vibrio cholerae RTX toxin gene cluster that is tightly linked to the cholera toxin prophage

Wei Lin, Karla Jean Fullner, Rebecca Clayton, Jessica A. Sexton, Marc B. Rogers, Kerstin E. Calia, Stephen B. Calderwood, Claire Fraser, John J. Mekalanos*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

231 Scopus citations

Abstract

We identify and characterize a gene cluster in El Tor Vibrio cholerae that encodes a cytotoxic activity for HEp-2 cells in vitro. This gene cluster contains four genes and is physically linked to the cholera toxin (CTX) element in the V. cholerae genome. We demonstrate by using insertional mutagenesis that this gene cluster is required for the cytotoxic activity. The toxin, RtxA, resembles members of the RTX (repeats in toxin) toxin family in that it contains a GD-rich repeated motif. Like other RTX toxins, its activity depends on an activator, RtxC, and an associated ABC transporter system, RtxB and RtxD. In V. cholerae strains of the classical biotype, a deletion within the gene cluster removes rtxC and eliminates cytotoxic activity. Other strains, including those of the current cholera pandemic, contain a functional gene cluster and display cytotoxic activity. Thus, the RTX gene cluster in El Tor O1 and O139 strains might have contributed significantly to their emergence. Furthermore, the RTX toxin of V. cholerae may be associated with residual adverse properties displayed by certain live, attenuated cholera vaccines.

Original languageEnglish (US)
Pages (from-to)1071-1076
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number3
DOIs
StatePublished - Feb 2 1999

ASJC Scopus subject areas

  • General

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