Genomic plasticity associated with antimicrobial resistance in Vibrio cholerae

Abstract

Significance Emergence of multidrug-resistant (MDR) pathogens and decreasing effectiveness of antibiotics pose a global threat to public health. Horizontally acquired genetic elements are the major players in the antibiotic resistance crisis. The importance of horizontal gene transfer (HGT) in V. cholerae evolution has been well-accepted since the 1980s, when it was reported that intestinal colonization and regulation of cholera toxin production are due to horizontally acquired functions. We show that V. cholerae is evolving continuously by gaining fitness traits through HGT. Our results show that more than 99% of recent V. cholerae isolates are MDR and their genome is enriched with acquired genetic elements. We further find that the expression pattern of resistance genes does not change whether or not antibiotic is present in a growth medium. The Bay of Bengal is known as the epicenter for seeding several devastating cholera outbreaks across the globe. Vibrio cholerae, 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 V. cholerae 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 V. cholerae. Here we present details of AMR profiles of 443 V. cholerae 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) V. cholerae 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 V. cholerae 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 V. cholerae evolution and management of cholera disease by providing clinical guidance on preferred treatment regimens.