title: Origins of the current seventh cholera pandemic.
abstract: Vibrio cholerae has caused seven cholera pandemics since 1817, imposing terror on much of the world, but bacterial strains are currently only available for the sixth and seventh pandemics. The El Tor biotype seventh pandemic began in 1961 in Indonesia, but did not originate directly from the classical biotype sixth-pandemic strain. Previous studies focused mainly on the spread of the seventh pandemic after 1970. Here, we analyze in unprecedented detail the origin, evolution, and transition to pandemicity of the seventh-pandemic strain. We used high-resolution comparative genomic analysis of strains collected from 1930 to 1964, covering the evolution from the first available El Tor biotype strain to the start of the seventh pandemic. We define six stages leading to the pandemic strain and reveal all key events. The seventh pandemic originated from a nonpathogenic strain in the Middle East, first observed in 1897. It subsequently underwent explosive diversification, including the spawning of the pandemic lineage. This rapid diversification suggests that, when first observed, the strain had only recently arrived in the Middle East, possibly from the Asian homeland of cholera. The lineage migrated to Makassar, Indonesia, where it gained the important virulence-associated elements Vibrio seventh pandemic island I (VSP-I), VSP-II, and El Tor type cholera toxin prophage by 1954, and it then became pandemic in 1961 after only 12 additional mutations. Our data indicate that specific niches in the Middle East and Makassar were important in generating the pandemic strain by providing gene sources and the driving forces for genetic events.
authors.affiliation: TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin Economic-Technological Development Area, Tianjin 300457, People's Republic of China.|The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Tianjin 300457, People's Republic of China.
authors.forename: Dalong
authors.initials: D
authors.lastname: Hu
authors.affiliation: TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin Economic-Technological Development Area, Tianjin 300457, People's Republic of China.|Tianjin Research Center for Functional Genomics and Biochip, Tianjin 300457, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin Economic-Technological Development Area, Tianjin 300457, People's Republic of China.|The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Tianjin 300457, People's Republic of China.|Tianjin Key Laboratory of Microbial Functional Genomics, Tianjin 300457, People's Republic of China.
authors.forename: Lu
authors.initials: L
authors.lastname: Feng
authors.affiliation: TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin Economic-Technological Development Area, Tianjin 300457, People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Ding
authors.affiliation: TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin Economic-Technological Development Area, Tianjin 300457, People's Republic of China.
authors.forename: Xi
authors.initials: X
authors.lastname: Guo
authors.affiliation: TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin Economic-Technological Development Area, Tianjin 300457, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin Economic-Technological Development Area, Tianjin 300457, People's Republic of China.|The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Tianjin 300457, People's Republic of China.|Tianjin Key Laboratory of Microbial Functional Genomics, Tianjin 300457, People's Republic of China.
authors.forename: Boyang
authors.initials: B
authors.lastname: Cao
authors.affiliation: School of Life and Environmental Sciences, University of Sydney, Sydney, NSW 2006, Australia; wanglei@nankai.edu.cn peter.reeves@sydney.edu.au.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Reeves
authors.affiliation: TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin Economic-Technological Development Area, Tianjin 300457, People's Republic of China; wanglei@nankai.edu.cn peter.reeves@sydney.edu.au.|The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Tianjin 300457, People's Republic of China.|Tianjin Key Laboratory of Microbial Functional Genomics, Tianjin 300457, People's Republic of China.|State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
mesh_terms: D002771:Cholera / Q000453:epidemiology* / Q000382:microbiology; D019143:Evolution, Molecular; D016680:Genome, Bacterial; D006801:Humans; D058977:Molecular Sequence Annotation; D058873:Pandemics; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D014734:Vibrio cholerae / Q000235:genetics*
keywords: Vibrio cholerae; comparative genomics; evolution; pandemic