Genomic plasticity associated with antimicrobial resistance in <i>Vibrio cholerae</i>

Abstract

The Bay of Bengal is known as the epicenter for seeding several devastating cholera outbreaks across the globe. <i>Vibrio cholerae</i>, the etiological agent of cholera, has extraordinary competency to acquire exogenous DNA by horizontal gene transfer (HGT) and adapt them into its genome for structuring metabolic processes, developing drug resistance, and colonizing the human intestine. Antimicrobial resistance (AMR) in <i>V. cholerae</i> has become a global concern. However, little is known about the identity of the resistance traits, source of AMR genes, acquisition process, and stability of the genetic elements linked with resistance genes in <i>V. cholerae</i> Here we present details of AMR profiles of 443 <i>V. cholerae</i> strains isolated from the stool samples of diarrheal patients from two regions of India. We sequenced the whole genome of multidrug-resistant (MDR) and extensively drug-resistant (XDR) <i>V. cholerae</i> to identify AMR genes and genomic elements that harbor the resistance traits. Our genomic findings were further confirmed by proteome analysis. We also engineered the genome of <i>V. cholerae</i> to monitor the importance of the autonomously replicating plasmid and core genome in the resistance profile. Our findings provided insights into the genomes of recent cholera isolates and identified several acquired traits including plasmids, transposons, integrative conjugative elements (ICEs), pathogenicity islands (PIs), prophages, and gene cassettes that confer fitness to the pathogen. The knowledge generated from this study would help in better understanding of <i>V. cholerae</i> evolution and management of cholera disease by providing clinical guidance on preferred treatment regimens.