Identification of a Vibrio cholerae RTX toxin gene cluster that is tightlylinked to the cholera toxin prophage

We identify and characterize a gene cluster in Fl Tor Vibrio cholerae that encodes a cytotoxic activity for HEp-2 cells in vitro, This gene cluster co ntains four genes and is physically linked to the cholera toxin (CTX) eleme nt in the V. cholerae genome. We demonstrate by using insertional mutagenes is that this gene cluster is required for the cytotoxic activity, The toxin , RtxA, resembles members of the RTX (repeats in toxin) toxin family in tha t it contains a GD-rich repeated motif, Like other RTX toxins, its activity depends on an activator, RtxC, and an associated ABC transporter system, R txB and RtxD, In V. cholerae strains of the classical biotype, a deletion w ithin the gene cluster removes rtxC and eliminates cytotoxic activity. Othe r strains, including those of the current cholera pandemic, contain a funct ional gene cluster and display cytotoxic activity. Thus, the RTX gene clust er in Fl Tor O1 and O139 strains might have contributed significantly to th eir emergence. Furthermore, the RTX toxin of V. cholerae may be associated with residual adverse properties displayed by certain live, attenuated chol era vaccines.