Origins of the current seventh cholera pandemic

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.

自1817年以来，Vibrio Cholerae造成了七个霍乱大流行，对世界上的大部分地区都施加了恐怖，但细菌菌株目前仅适用于第六和第七大流行。 El tor Biotype第七型大流行始于1961年在印度尼西亚，但并非直接源自经典的生物型第六大流血菌株。先前的研究主要集中于1970年以后第七次大流行的传播。在这里，我们以前所未有的细节分析了第七大菌株的大流行性的起源，进化和过渡。我们对从1930年至1964年收集的菌株进行了高分辨率比较基因组分析，涵盖了从第一个可用的El Tor Biotype菌株到第七大流行的开始。我们定义导致大流行菌株的六个阶段，并揭示所有关键事件。第七次大流行起源于中东的非人病菌株，于1897年首次观察到。随后进行了爆炸性多样化，包括大流行谱系的产卵。这种快速的多元化表明，当第一次观察到这种菌株直到最近才到达中东，可能是从霍乱的亚洲祖国到达。该血统迁移到印度尼西亚的Makassar，在那里获得了重要的毒力相关元素颤音第七群岛I（VSP-I），VSP-II和El Tor Type Cholera Type Type Cholera Toxin Toxin Prophage，然后仅在12个额外的突变之后才在1961年大流行。我们的数据表明，中东和Makassar的特定生态位对于通过提供基因来源和遗传事件的驱动力来产生大流行菌株很重要。