Genomic insights into epidemic plasmids carrying bla (CTX-M) and mcr-1 genes in Escherichia coli from Lebanese broiler production

对黎巴嫩肉鸡生产中大肠杆菌携带 bla (CTX-M) 和 mcr-1 基因的流行质粒的基因组学研究

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Abstract

BACKGROUND: In a previous nationwide survey in the Lebanese broiler production, multidrug-resistant CTX-M-producing E. coli were found to carry the mobile colistin resistance gene mcr-1. OBJECTIVES: To investigate the mobile genetic supports responsible for the spread of these resistance genes among E. coli in healthy broilers in Lebanon. METHODS: Thirty-three bla (CTX-M) and mcr-1 positive E. coli of various sequence types from 17 broilers farms were subjected to conjugation assays. Long-read sequencing (Oxford Nanopore Technologies) and hybrid assembly were performed to determine complete plasmid sequences and their phylogenetic diversity. RESULTS: Twenty-nine conjugative IncFII plasmids harboured the extended-spectrum β-lactamase genes bla (CTX-M-3) (n = 25) or bla (CTX-M-55) (n = 4). Highly related IncF2:A-:B-/bla (CTX-M-3) plasmids differing only through IS-mediated genetic rearrangements in antibiotic resistance gene clusters were found in genetically diverse E. coli strains isolated from distant farms. The mobile colistin resistance genes mcr-1.1 and mcr-1.26 were carried by IncX4 and IncI2 plasmids. Worryingly, in one isolate, the ISEcp1-bla (CTX-M-55) transposable unit was found integrated in a mcr-1.26-carrying IncX4 plasmid. Beside expanded cephalosporins and colistin resistances, all E. coli isolates were multidrug-resistant with different additional resistances against aminoglycosides, (fluoro)quinolones, fosfomycin, phenicols, sulphonamides, tetracycline and trimethoprim. CONCLUSIONS: Closely related blaCTX-M-3/55-borne IncF2:A-:B- plasmids harbouring variable MDR regions and mcr-1 carrying IncX4 plasmids are widely disseminated in the E. coli population of healthy broilers in Lebanon. Further surveillance programmes of antimicrobial resistance and interventions to reduce the abusive use of medically important antibiotics are necessary to limit the spread of resistances in food-producing animals in Lebanon.

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