Kappa Prophage Impacts Vibrio cholerae Fitness and is Restricted by BREX Phage Defense System

Abstract

Vibrio cholerae's pathogenicity largely stems from the acquisition of cholera toxin genes via lysogenic conversion mediated by the CTX prophage. However, the strong association of other prophages with epidemic strains has not been linked to lysogenic conversion. During the first wave of the seventh cholera pandemic, the Kappa prophage was commonly found in clinical isolates and was later shown to confer a competitive fitness advantage in the environment and to accelerate evolution by stimulating horizontal gene transfer; however, its role in virulence remains unknown. Here, we report that the Kappa prophage confers a competitive fitness advantage in vitro and during intestinal tract infection in both Wave 1 and Wave 3 strains. This competitive fitness advantage is due to phage predation on neighboring cells, and not to lysogenic conversion. Furthermore, we show that loss of Kappa coincides with the acquisition of novel phage defense systems from SXT ICEs VchBan9 and VchInd5. Phage defense systems BREX and AbiC inhibited Kappa predation and restricted horizontal gene transfer, thereby reducing Kappas competitive fitness advantage.