Vibrio cholerae evolved a multifaceted adaptive strategy in response to predation by a novel ICP1 bacteriophage in a cholera-endemic region of the Democratic Republic of the Congo

Cholera remains a major global cause of morbidity and mortality. Bacteriophage predation of toxigenic Vibrio cholerae O1 (the causative agent of cholera) has been linked with seasonal patterns of disease and with clinical response to infection in humans 1-4. However, we still lack a clear demonstration of how the interplay between bacteria and bacteriophage can influence long-term shifts in strain populations. We report here use of Bayesian phylogeography to initially characterize toxigenic V. cholerae O1 isolated from patients in the Great Lakes region of the Democratic Republic of the Congo (DRC). Two major epidemic clades were identified, with the most recent correlating to ST515, a previously cholera population found in the Lake Kivu and expanding northward5; all strains were derived from the East Africa T10 introduction6, consistent with establishment of a regional endemic focus. In assessing evolutionary drivers for this strain population, we identified a novel ICP1 bacteriophage, genetically distinct from previous ICP1 isolates detected in Asia 7,8, from stool samples of cholera patients. Phylogenomic analyses indicate that this V. cholerae population evolved a multifaceted adaptive strategy to resist phage predation. Furthermore, we describe two genes that appear to work as an on/off switch to resistance provided by an heterogenous genetic landscape. Our data highlight the complex co-evolution of bacteriophage and bacteria occurring in this setting.