RESUMEN
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.
Asunto(s)
Cólera/microbiología , Farmacorresistencia Bacteriana Múltiple/genética , Transferencia de Gen Horizontal , Genoma Bacteriano/genética , Vibrio cholerae/genética , Antibacterianos/farmacología , Conjugación Genética/genética , Elementos Transponibles de ADN/genética , Diarrea/microbiología , Evolución Molecular , Heces/microbiología , Variación Genética , Islas Genómicas/genética , Humanos , Imipenem/farmacología , India , Secuencias Repetitivas Esparcidas/genética , Fenotipo , Plásmidos/genética , Profagos/genética , Proteoma , Vibrio cholerae/efectos de los fármacos , Vibrio cholerae/aislamiento & purificación , Vibrio cholerae/patogenicidad , Vibrio cholerae O1/genética , Vibrio cholerae O1/aislamiento & purificación , Vibrio cholerae O1/patogenicidad , Secuenciación Completa del GenomaRESUMEN
Emergence of antimicrobial resistant Gram-negative bacteria has created a serious global health crisis and threatens the effectiveness of most, if not all, antibiotics commonly used to prevent and treat bacterial infections. There is a dearth of detailed studies on the prevalence of antimicrobial resistance (AMR) patterns in India. Here, we have isolated and examined AMR patterns of 654 enteric pathogens and investigated complete genome sequences of isolates from six representative genera, which in aggregate encode resistance against 22 antibiotics representing nine distinct drug classes. This study revealed that ~97% isolates are resistant against ≥2 antibiotics, ~24% isolates are resistant against ≥10 antibiotics and ~3% isolates are resistant against ≥15 antibiotics. Analyses of whole genome sequences of six extensive drug resistant enteric pathogens revealed presence of multiple mobile genetic elements, which are physically linked with resistance traits. These elements are therefore appearing to be responsible for disseminating drug resistance among bacteria through horizontal gene transfer. The present study provides insights into the linkages between the resistance patterns to certain antibiotics and their usage in India. The findings would be useful to understand the genetics of resistance traits and severity of and difficulty in tackling AMR enteric pathogens.
