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Over the last 120 years or so there have been seven cholera pandemics. Vaccines from killed bacteria do not give lasting immunity and therefore present research is concentrated on live vaccines. A new discovery at Harvard (Matthew K Waldor and John J Mekalanos, Science 1996;272:1910-4) has important implications for vaccine development as well as for bacterial science (Nigel Williams, Science1996;272:1869-70). Most cholera bacteria are benign but virulent strains can transmit the capacity for toxin production horizontally to other strains. and Waldor and Mekalanos have shown that this transmission is accomplished by a filamentous bacteriophage. A section of DNA within the bacterial chromosome, known as the CTX element, contains at least six genes including the toxin gene and it is this CTX segment which is transmitted by the phage. Toxin production and the formation of bacterial cell surface pili, which are responsible for gut wall adherence, are both regulated by a single bacterial gene, toxR. The CTX-containing phage gains entry to the bacterial cell via the pili which act as receptors; cells without pili are resistant to the phage. Clearly the potential for horizontal transmission of toxin production is very worrying to vaccine developers but non-pili expressing strains may be safer. (The El Tor strain is less liable to produce pili than are classical strains). Other organisms such as salmonella or yersinia could possibly acquire virulence factors in a similar way. The genetic coregulation of toxin production and pili formation points to the evolutionary interdependence of phage and bacterium working to preserve phage DNA.
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