We investigated the prevalence and the antimicrobial resistance genes pool in ESBL-producing E. coli from pig farms in Vietnam. From 116 pig farms, we collected 116 composite pig fecal samples and 94 individual fecal samples from pig farm workers. Indicator E. coli and ESBL-producing E. coli were isolated on MacConkey agar plates with and without cefotaxim (2 mg/l). Antimicrobial resistance was tested to 12 antimicrobials by disk diffusion. Resistance to colistin was tested by micro-broth dilution and double disk synergy test was done to confirm ESBL. ESBL-producing E. coli were isolated 43/58 (74%) and 78/87 (90%) fecal samples from workers and pigs, respectively. Whole genome sequencing was performed to analyze the genomes of 74 ESBL-producing E. coli isolated from pigs and farm workers. The ESBL genes detected were blaCTX-M-55, blaCTX-M-27, blaCTX-M-15, blaCTX-M-14, blaCTX-M-3, blaCTX-M-65, blaCTX-M-24, blaOXA-10, blaCARB2 and two AmpC genes blaDHA-1 and blaCMY2. Eighteen of the 43 ESBL E. coli from pigs carried colistin resistance (mcr-1, mcr-3) and quinolone resistance (both plasmid-mediated and chromosomal mutations) genes. Four of the 31 ESBL isolates from humans harbored resistance genes for colistin and quinolone. Resistance to aminoglycosides, sulfonamides, trimethoprim, tetracycline, chloramphenicol, fosfomycin and rifampicin was present in most of the ESBL isolates. The virulence genes profile of the sequenced ESBL isolates revealed that they were mostly commensal E. coli. This is substantiated by a high heterogeneity among the ESBL-producing E. coli from pigs and workers belonging to unrelated phylogroups, serogroups, and sequence types and the strains did not show any pattern of similarity according to the farms with no evidence of transfer between pigs and humans. The phylogenetic tree revealed three distinct clades with more than 1000 SNPs between isolates in each clade. The occurrence of ESBL/AmpC genes along with colistin and quinolone resistance genes of various plasmids..? in varying commensal E. coli in pig farms constitute a potential health risk as they could be horizontally transferred to bacterial pathogens
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