Revisiting the Genomic Epidemiology of Distinct Phage-Type Vibrio cholerae Strains Reveals Restricted Spatiotemporal Dissemination During an Epidemic

The El Tor biotype of <i>Vibrio cholerae</i> caused the seventh cholera pandemic (7CP). Although <i>V. cholerae</i> variants of this biotype frequently emerge, studies on their microevolution and spatiotemporal transmission in epidemics caused by a single clone are limited. During the cholera outbreak in Sichuan Province, China, in the 1990s, strains belonging to phage type 6 (PT6) but resistant to typing phage VP5 due to a deletion mutation in <i>ompW</i>, which is the gene associated with the VP5 receptor were identified. In this study, we analyzed PT6 strains using genome sequencing to reveal the genomic and transmission characteristics of such a transient phage type in China's cholera epidemic history. The findings revealed that the PT6 strains formed an independent clone during the four-year epidemic and emerged in wave 2. Most of them carried multiple CTX^classΦ genome copies on chromosome 2 (Chr. 2) and two copies each of RS1^ET and RS1-4** on chromosome 1 (Chr. 1). Frequent cross-regional transmission and local outbreaks within Sichuan Province, China, were revealed for this clone. A variety of spontaneous mutations in the <i>ompW</i> gene, conferring resistance to the VP5 phage, were observed under VP5 infection pressure, showing the incident mutation of OmpW for the survival adaptation of <i>V. cholerae</i> to phage pressure. Therefore, this genomic epidemiological revisit of these distinct phage-resistant phenotype strains reveals their clonal genetic structure, improves our understanding of the spread of <i>V. cholerae</i> by tracking their variation, and assists in epidemic source tracing and disease control.