Genome Dynamics of Vibrio cholerae Isolates Linked to Seasonal Outbreaks of Cholera in Dhaka, Bangladesh

Abstract

The temporal switching of serotypes from serotype Ogawa to Inaba and back to Ogawa was identified in <i>Vibrio cholerae</i> O1, which was responsible for seasonal outbreaks of cholera in Dhaka during the period 2015 to 2018. In order to delineate the factors responsible for this serotype transition, we performed whole-genome sequencing (WGS) of <i>V. cholerae</i> O1 multidrug-resistant strains belonging to both the serotypes that were isolated during this interval where the emergence and subsequent reduction of the Inaba serotype occurred. The whole-genome-based phylogenetic analysis revealed clonal expansion of the Inaba isolates mainly responsible for the peaks of infection during 2016 to 2017 and that they might have evolved from the prevailing Ogawa strains in 2015 which coclustered with them. Furthermore, the <i>wbeT</i> gene in these Inaba serotype isolates was inactivated due to insertion of a transposable element at the same position signifying the clonal expansion. Also, <i>V. cholerae</i> isolates in the Inaba serotype dominant clade mainly contained classical <i>ctxB</i> allele and revealed differences in the genetic composition of <i>Vibrio</i><u>s</u>eventh <u>p</u>andemic <u>i</u>sland II (VSP-II) and the SXT integrative and conjugative element (SXT-ICE) compared to those of Ogawa serotype strains which remerged in 2018. The variable presence of phage-inducible chromosomal island-like element 1 (PLE1) was also noted in the isolates of the Inaba serotype dominant clade. The detailed genomic characterization of the sequenced isolates has shed light on the forces which could be responsible for the periodic changes in serotypes of <i>V. cholerae</i> and has also highlighted the need to analyze the mobilome in greater detail to obtain insights into the mechanisms behind serotype switching.<b>IMPORTANCE</b> The switching of serotype from Ogawa to Inaba and back to Ogawa has been observed temporally in <i>Vibrio cholerae</i> O1, which is responsible for endemic cholera in Bangladesh. The serospecificity is key for effective intervention and for preventing cholera, a deadly disease that continues to cause significant morbidity and mortality worldwide. In the present study, WGS of <i>V. cholerae</i> allowed us to better understand the factors associated with the serotype switching events observed during 2015 to 2018. Genomic data analysis of strains isolated during this interval highlighted variations in the genes <i>ctxB</i>, <i>tcpA</i>, and <i>rtxA</i> and also identified significant differences in the genetic content of the mobilome, which included key elements such as SXT ICE, VSP-II, and PLE. Our results indicate that selective forces such as antibiotic resistance and phage resistance might contribute to the clonal expansion and predominance of a particular <i>V. cholerae</i> serotype responsible for an outbreak.