Genomic characteristics of recently recognized Vibrio cholerae El Tor lineages associated with cholera in Bangladesh, 1991-2017

Abstract

Comparative genomic analysis of Vibrio cholerae El Tor associated with endemic cholera in Asia revealed two distinct lineages, one dominant in Bangladesh and the other in India. An in depth whole genome study of V. cholerae El Tor clinical strains isolated during endemic cholera in Bangladesh (1991 – 2017) included reference genome sequence data obtained online. Core genome phylogeny established using single nucleotide polymorphisms (SNPs) showed V. cholerae El Tor strains comprised two lineages, BD-1 and BD-2, which, according to Bayesian phylodynamic analysis, originated from paraphyletic group BD-0 around 1981. BD-1 and BD-2 lineages overlapped temporally but were negatively associated as causative agents of cholera 2004-2017. Genome wide association study (GWAS) revealed 140 SNPs and 31 indels, resulting in gene alleles unique to BD-1 and BD-2. Regression analysis of root to tip distance and year of isolation indicated early BD-0 strains at the base, whereas BD-1 and BD-2 subsequently emerged and progressed by accumulating SNPs. Pangenome analysis provided evidence of gene acquisition by both BD-1 and BD-2, of which six crucial proteins of known function were predominant in BD-2. BD-1 and BD-2 diverged and have distinctively different genomic traits, namely heterogeneity in VSP-2, VPI-1, mobile elements, toxin encoding elements, and total gene abundance. In addition, the observed phage-inducible chromosomal island-like element (PLE1), and SXT ICE elements (ICETET) in BD-2 presumably provided a fitness advantage for the lineage to outcompete BD-1 as the etiological agent of the endemic cholera in Bangladesh, with implications for global cholera epidemiology.ImportanceCholera is a global disease with specific reference to the Bay of Bengal Ganges Delta where Vibrio cholerae O1 El Tor, causative agent of the disease showed two circulating lineages, one dominant in Bangladesh and the other in India. Results of in-depth genomic study of V. cholerae associated with endemic cholera during the past 27 years (1991 – 2017) indicate emergence and succession of the two lineages, BD-1 and BD-2, arising from a common ancestral paraphylatic group, BD-0, comprising the early strains and short-term evolution of the bacterium in Bangladesh. Among the two V. cholerae lineages, BD-2 supersedes BD-1 and is predominant in the most recent endemic cholera in Bangladesh. The BD-2 lineage contained significantly more SNPs and indels, and showed richness in gene abundance, including antimicrobial resistance genes, gene cassettes, and PLE to fight against bacteriophage infection, acquired over time. These findings have important epidemic implications at a global scale.

Genomic attributes of Vibrio cholerae responsible for a massive cholera outbreak in Bangladesh, 2022

“…Intense niche competition with BD-2 strains may account for this turn of events. In addition, the BD-1.2 strains proved to be genetically different from recently recognized transmission lineages T11-13 and LAT-3 12,15 and circulating lineages in Bangladesh 10 . They carried unique mutations in several genes playing a critical role in promoting growth, resistance to bile salt, cell wall organization, and toxigenicity, presumably selectively advantageous for this subclade.…”

“…In this study, we investigated genomic attributes of V. cholerae O1 El Tor associated with the 2022 massive cholera outbreak in Dhaka, Bangladesh. A genomic analysis of outbreak strains isolated from admitted patients at icddr,b hospital was done, including comparative genomic analysis of sequence data of earlier studies 8,10,12,15 in 88 countries from 1957 to 2022. The results provided evidence for 7 th pandemic El Tor wave-3 global clade strains forming a new subclade, designated BD-1.2, tracing to a most recent common ancestor, namely a globally distributed 7 th pandemic El Tor lineage predominantly associated with recent endemic cholera in India.…”

“…Both BD-1.1 and BD-1.2 comprise component of a global clade that includes strains associated with cholera world-wide, e.g., Haiti 13 and Yemen 14 . The Bangladesh BD-1.2 strains initiated a massive cholera outbreak in 2022 displacing BD-2 strains locally dominant at the time 10 . Intense niche competition with BD-2 strains may account for this turn of events.…”

“…The whole-genome sequence analysis of V. cholerae O1 El Tor strains associated with endemic cholera in Dhaka, Bangladesh, and Kolkata, India, showed two circulating lineages, one dominant in India and the other in Bangladesh 8 . To understand its evolutionary dynamics, a temporal genomic study of V. cholerae associated with endemic cholera in Dhaka, Bangladesh (1991 -2017) was undertaken 10 . Results revealed distinct genomic attributes for the two circulating lineages, BD-1 and BD-2 originating from a paraphyletic group BD-0.…”