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The gene encoding the cholera toxin was introduced into V. cholerae by horizontal gene transfer. Virulent strains of V. cholerae (the O1 and O139 Serogroups) hold a genes from a virus known as a CTXφ Bacteriophage (or RS1). The integrated CTXφ gene contains many of the genes of RS1, including elements for replication (RstA), integration (RstB), and regulation of gene expression (RstR), as well as genes coding for proteins needed for phage packaging and secretion (Psh, Cep, OrfU, Ace and Zot)

The sequences at the 5′ ends of integrated CTXφ and RS1 are essentially identical. They encode proteins used by both elements for replication (RstA), integration (RstB), and regulation of gene expression (RstR; Figure 1) [11]. The remaining genes of CTXφ encode proteins needed for phage packaging and secretion (Psh, Cep, OrfU, Ace and Zot), as well as CT, which does not contribute to virion formation. RS1 lacks these additional genes; however, since RS1 transmission is mediated by CTXφ-encoded proteins, it is believed that the two phages have essentially identical packaging, secretion, and infection processes 9.••, 12.. Instead of the phage morphogenesis proteins, RS1 encodes a novel protein, RstC, that was recently shown to be an antirepressor [9••].