期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2016
卷号：113
期号：48
页码：E7730-E7739
DOI：10.1073/pnas.1608732113
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceCholera, a major disease in human history, has terrorized the world through seven pandemics. The seventh pandemic started in Indonesia in 1961 and spread globally, currently infecting 3-5 million people annually. By combining all available historical records and genomic analysis of available preseventh pandemic and some early pandemic strains, we revealed the complex six-step evolution of the pandemic strain from its probable origin in South Asia to its nonpathogenic form in the Middle East in [~]1900 to Indonesia in [~]1925, where it evolved into a pandemic strain before becoming widespread in 1961. This pathway relates to human traffic routes, including the annual Hajj pilgrimage, and involved novel niches that provided gene sources and the driving forces for stepwise evolution. 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.
