EMERGENCE OF A NEW CHOLERA PANDEMIC - MOLECULAR ANALYSIS OF VIRULENCE DETERMINANTS IN VIBRIO-CHOLERAE O139 AND DEVELOPMENT OF A LIVE VACCINE PROTOTYPE

In October 1992, a non-O1 strain of Vibrio cholerae emerged as a cause of epidemic cholera in India and Bangladesh. This antigenically novel clone has been designated serogroup O139 synonym Bengal. Since its emergence, V. cholerae O139 has caused a massive cholera epidemic throughout and beyond the Indian subcontinent. Molecular analysis of virulence determinants in clinical isolates suggests that O139 strains are highly related to El Tor O1 strains. Unlike other non-O1 strains, O139 strains carry multiple copies of the cholera toxin genetic element and also genes for the toxin-coregulated pilus. These results guided construction of a live V. cholerae O139 vaccine prototype through deletion of genes for at least four specific virulence determinants (ctxA, ace, tot, and cep) as well as other factors involved in site-specific and homologous recombination (RS1, attRS1, and recA). It is hoped that this attenuated live vaccine will help control the pandemic spread of V. cholerae O139.