A bacteriophage encoding a pathogenicity island, a type-IV pilus and a phage receptor in cholera bacteria

The virulence properties of many pathogenic bacteria are due to proteins encoded by large gene clusters called pathogenicity islands1,2, which are found in a variety of human pathogens including Escherichia coli, Salmonella, Shigella, Yersinia, Helicobacter pylori, Vibrio cholerae, and animal and plant pathogens such as Dichelobacter nodosus and Pseudomonas syringae1,2,3. Although the presence of pathogenicity islands is a prerequisite for many bacterial diseases, little is known about their origins or mechanism of transfer into the bacterium. The bacterial agent of epidemic cholera, Vibrio cholerae , contains a bacteriophage known as cholera-toxin phage (CTXφ)4, which encodes the cholera toxin, and a large pathogenicity island called the VPI (for V. cholerae pathogenicity island)5 which itself encodes a toxin-coregulated pilus that functions as a colonization factor6 and as a CTXφ receptor4. We have now identified the VPI pathogenicity island as the genome of another filamentous bacteriophage, VPIφ. We show that VPIφ is transferred between V. cholerae strains and provide evidence that the TcpA subunit of the toxin-coregulated type IV pilus is in fact a coat protein of VPIφ. Our results are the first description of a phage that encodes a receptor for another phage and of a virus–virus interaction that is necessary for bacterial pathogenicity.