Origin and relationships of the current Cholera El Tor pandemic Clone. Vibrio cholerae

Vibrio cholera is one of the most important human pathogens globally, giving rise to seven cholera pandemics since 1817. The 5th and 6th pandemics were caused by the classical biotype, while the on-going 7th pandemic, starting in 1961, is caused by an El Tor biotype clone. The recent 7th pandemic outbreak in Haiti infected over 380,000 people and caused over 5,800 deaths.It has been shown that the 6th and 7th pandemic clones arose independently from a common lineage, and about 30% of the genome underwent recombination during divergence. Despite much research, it is still not clear how the 7th pandemic originated.Several El Tor isolates from 1910 to 1959 are related to the 7th pandemic clone. Here we present new genome sequences of pre-pandemic isolates, including from the last pre-pandemic outbreak, and three early 7th pandemic isolates. Genome comparisons show that transition from pre-pandemic to 7th pandemic involved very little genetic change, although patterns of evolutionary change before and after the transition are also very different. For instance, recombination is frequent in the pre-pandemic period, but very low in the 7th pandemic, implying a change in its niche. We also present a map of the migration from Middle East via Makassar in Indonesia to a global pandemic, and long distance transmission from the Middle East to the USA and from Makassar to Australia. Our work fills a critical gap in knowledge of V. cholerae evolution from the appearance of the El Tor clone to emergence of the 7th pandemic.