PHYLOGENOMIC AND STRUCTURAL ANALYSES OF VIBRIO CHOLERAE POPULATIONS AND ENDEMIC CHOLERA

Abstract

Cholera is a serious public health problem because of the high burden of morbidity. Recurrent pandemic cholera is sustained by an endemic epicenter in the Bay of Bengal region but the mechanism of endemism is not clearly understood. Recent information showing that the dynamics and seasonality of endemic cholera are linked with environmental parameters led to the hypothesis that the population dynamics of V. cholerae, the causative agent of cholera indigenous in natural aquatic environments, is the link causing variation in endemic cholera. To substantiate this hypothesis, the structure and dynamics of V. cholerae populations in the aquatic environments were investigated, employing three approaches. First, the phylogeny of the family Vibrionaceae was analyzed to determine the phylogenetic boundary of V. cholerae. Phylogeny analysis using comparative genomics revealed that the species, V. cholerae, is a direct descendant of a common ancestor of the genus, with at least 25% of its genome subject to horizontal gene transfer from other vibrios. The second approach was analysis of the population structure of V. cholerae using genomic fingerprinting, with the conclusion that there is a multilayered clonality and paraphyla within the species, with a subvar branch, V. mimicus. It was also concluded that all of the epidemic lineages of V. cholerae are highly clonal, forming a tight phylogenetic compartment. The nonpathogenic clones were found to be highly diverse and some showed significant association with fluctuations observed in the potential-host crustacean zooplankton compositions. Finally, analyses of both the dynamics and compartmentalization of V. cholerae populations during endemic cholera outbreaks yielded a compartmentalized understanding of the mechanism of endemic cholera, namely that there are bodies of water in a cholera endemic area that serve as a reservoir of the bacterium and, therefore, a point source for the seasonal spread of cholera bacteria. The nature of a universal seasonal forcing that repeats the spread of the cholera bacterium from the point source each cholera season is not clear. Further study is recommended to identify those factors that determine both the point source reservoir and the mode of transportation resulting in spread of contaminated water from the reservoir.