1113. Real-Time Evolution of Extensively Drug-Resistant Vibrio cholerae

BACKGROUND: Bay of Bengal is known as the epicenter of a number of distinct waves of global transmission of cholera. Vibrio cholerae, the etiological agent of acute diarrhoeal disease cholera, has extraordinary competency to acquire exogenous DNA by horizontal gene transfer (HGT) and acclimatize them into their genome for structuring metabolic process, developing drug resistance and disease. Antimicrobial resistance (AMR) in V. cholerae is a global concern. However, little is known about the identity, source, acquisition process, and stability of the resistance traits in the genome of cholera pathogen. METHODS: Antibiotic susceptibility testing of V. cholerae isolated from different parts of India during 2001–2017 was performed using Discs and E-strips. Whole-genome sequencing of resistant (R), multidrug resistant (MDR), extensively drug resistant (XDR), and pandrug (PDR) resistant V. cholerae was done by next-generation DNA sequencing. Mobile genetic elements (MGEs) linked with AMR genes were tagged by allelic exchange methods. Whole-cell proteome analysis was done by iTRAQ analysis. RESULTS: Almost 99% of V. cholerae isolates (n = 438) are resistant against ≥2 antibiotics, 17.2% isolates (n = 76) are resistant against ≥10 antibiotics, and 7.5% isolates (n = 33) are resistant against ≥14 antibiotics. Highest resistance was detected against sulfamethaxozole (99.8%, n = 442). In addition, resistance to nalidixic acid (n = 429), trimethoprim (n = 421), and streptomycin (n = 409) are also very high. All the sequenced resistant isolates carrying multiple resistance genes and are linked with MGEs like integrating conjugative elements, transposons etc. Most of the resistance traits are functional and expressed even in the absence of antibiotics. CONCLUSION: Our comprehensive analysis of 443 clinical V. cholerae isolates show that the cholera pathogen is continuously evolving to counterbalance the antimicrobial effects of antibiotics. Several MGEs linked with AMR genes and other fitness factors potentially propagate to other bacterial species through HGTs. Knowledge of the present study would be useful to understand the evolution of cholera pathogens and management of cholera by helping selection of specific drug regimen against the pathogens. DISCLOSURES: All authors: No reported disclosures.