Although cholera is an ancient disease that first arose at least half a millennium ago, it remains a major health threat globally. Its pandemic form is caused by strains from a single lineage of the bacterium Vibrio cholerae. The ancestor of this lineage harbored several distinctive characteristics, the most notable being the O1 antigen polysaccharide. This lineage generated two biotypes, first Classical, responsible for six pandemics, and later El Tor, responsible for the seventh and ongoing pandemic. Just as El Tor replaced Classical as the main cause of outbreaks in the last fifty years, several variants of El Tor have evolved and displaced their predecessors worldwide. Understanding the ecology, evolution and dispersal of pandemic V. cholerae is central to studying this complex disease with environmental reservoirs. Here, we present recent advancements of our knowledge on the emergence and spread of the pandemic generating lineage of V. cholerae in the light of established eco-evolutionary observations. Specific ecological interactions shape seasonal cholera, playing a role in the abundance and distribution of its causative agent. Both species-specific and lineage-specific genetic determinants play a role in the ability of V. cholerae strains to cause pandemics with seasonal outbreaks, having evolved gradually over centuries. On the basis of the current understanding, we outline future threats and changes in biogeographical and genomic-based investigation strategies to combat this global problem.

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