Origins of Pandemic Cholera from Environmental Gene Pools (and its Fate within Patients)

Some microbes can transition from an environmental lifestyle to a pathogenic one. This ecological switch typically occurs through the acquisition of horizontally acquired virulence genes. However, the genomic features that must be present in a population prior to the acquisition of virulence genes and emergence of pathogenic clones remain unknown. We hypothesized that virulence adaptive polymorphisms (VAPs) circulate in environmental populations and are required for this transition. We developed a comparative genomic framework for identifying VAPs, using Vibrio cholerae as a model. We then characterized several environmental VAP alleles to show that, while some of them reduced the ability of clinical strains to colonize a mammalian host, other alleles conferred efficient host colonization. These results show that VAPs are present in environmental bacterial populations prior to the emergence of virulent clones. We propose a scenario in which VAPs circulate in the environment, they become selected and enriched under certain ecological conditions, and finally a genomic background containing several VAPs acquires virulence factors that allows for its emergence as a pathogenic clone.