Molecular Basis of the Toxigenic Vibrio cholerae O1 Serotype Switch from Ogawa to Inaba in Haiti.

Toxigenic Vibrio cholerae O1 serotype Ogawa was introduced involuntarily into Haiti in October 2010, and virtually all of the clinical strains isolated during the first 5 years of the epidemic were Ogawa. Inaba strains were identified intermittently prior to 2015, with diverse mutations resulting in a common phenotype. In 2015, the percentage of clinical infections due to the Inaba serotype began to rapidly increase, with Inaba supplanting Ogawa as the dominant serotype during the subsequent 4 years. We investigated the molecular basis of the serotype switch and confirmed that all Inaba strains had the same level of mRNA expression of the wbeT genes, as well as the same translation levels for the truncated WbeT proteins in the V. cholerae Inaba isolates. Neither wbeT gene expression levels, differential mutations, or truncation size of the WbeT proteins appeared to be responsible for the successful Inaba switch in 2015. Our phylodynamic analysis demonstrated that the V. cholerae Inaba strains in Haiti evolved directly from Ogawa strains and that a significant increase of diversifying selection at the population level occurred at the time of the Ogawa-Inaba switch. We conclude that the emergence of the Inaba serotype was driven by diversifying selection, independent of the mutational pattern in the wbeT gene. IMPORTANCE Our phylodynamic analysis demonstrated that Vibrio cholerae Inaba strains in Haiti evolved directly from Ogawa strains. Our results support the hypothesis that after an initial Ogawa-dominated epidemic wave, V. cholerae Inaba was able to become the dominant strain thanks to a selective advantage driven by ongoing diversifying selection, independently from the mutational pattern in the wbeT gene.