Dominant Vibrio cholerae phage exhibits lysis inhibition sensitive to disruption by a defensive phage satellite

Bacteriophages and their bacterial hosts are locked in a dynamic evolutionary arms race. Phage satellites, selfish genomic islands which exploit both host bacterium and target phage, further complicate the evolutionary fray. One such tripartite system involves the etiological agent of the diarrheal disease cholera, Vibrio cholerae, the predominant phage isolated from cholera patients, ICP1, and a phage satellite, PLE. When ICP1 infects V. cholerae harboring the integrated PLE genome, PLE accelerates host lysis, spreading the PLE while completely blocking phage production protecting V. cholerae at the population level. Here we identify a single PLE gene, lidI, sufficient to mediate accelerated lysis during ICP1 infection and demonstrate that LidI functions through disrupting lysis inhibition, an understudied outcome of phage infection when phages vastly outnumber their hosts. This work identifies ICP1-encoded holin and antiholin genes teaA and arrA respectively, that mediate this first example of lysis inhibition outside the T-even coliphages. Through lysis inhibition disruption, LidI is sufficient to limit the number of progeny phage produced from an infection. Consequently, this disruption bottlenecks ICP1 evolution as probed by recombination and CRISPR-Cas targeting assays. These studies link novel characterization of the classic phenomenon of lysis inhibition with a conserved protein in a dominant phage satellite, highlighting the importance of lysis timing during infection and parasitization, as well as providing insight into the populations, relationships, and evolution of bacteria, phages, and phage satellites in nature.