Abstract

ABSTRACTMobile genetic elements play a pivotal role in the adaptation of bacterial populations, allowing them to rapidly cope with hostile conditions, including the presence of antimicrobial compounds. IncA/C conjugative plasmids (ACPs) are efficient vehicles for dissemination of multidrug resistance genes in a broad range of pathogenic species of Enterobacteriaceae. ACPs have sporadically been reported in Vibrio cholerae, the infectious agent of the diarrheal disease cholera. The regulatory network that controls ACP mobility ultimately depends on the transcriptional activation of multiple ACP-borne operons by the master activator AcaCD. Beyond ACP conjugation, AcaCD has also recently been shown to activate the expression of genes located in the Salmonella genomic island 1 (SGI1). Here, we describe MGIVchHai6, a novel and unrelated mobilizable genomic island (MGI) integrated into the 3′ end of trmE in chromosome I of V. cholerae HC-36A1, a non-O1/non-O139 multidrug-resistant clinical isolate recovered from Haiti in 2010. MGIVchHai6 contains a mercury resistance transposon and an integron In104-like multidrug resistance element similar to the one of SGI1. We show that MGIVchHai6 excises from the chromosome in an AcaCD-dependent manner and is mobilized by ACPs. Acquisition of MGIVchHai6 confers resistance to β-lactams, sulfamethoxazole, tetracycline, chloramphenicol, trimethoprim, and streptomycin/spectinomycin. In silico analyses revealed that MGIVchHai6-like elements are carried by several environmental and clinical V. cholerae strains recovered from the Indian subcontinent, as well as from North and South America, including all non-O1/non-O139 clinical isolates from Haiti.

Highlights

  • Mobile genetic elements play a pivotal role in the adaptation of bacterial populations, allowing them to rapidly cope with hostile conditions, including the presence of antimicrobial compounds

  • Previous studies pointed out the major role of mobile genetic elements in propagation of multidrug resistance (MDR), notably conjugative elements such as conjugative plasmids and integrative and conjugative elements (ICEs) [5, 45,46,47]

  • Recent progress in deciphering the biology of SXT/R391 ICEs and antimicrobial compounds. IncA/C conjugative plasmids (ACPs) has refined our understanding of the biology of these major drivers of the distribution of MDR among the Gammaproteobacteria [7, 11, 21, 41, 48,49,50]

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Summary

Introduction

Mobile genetic elements play a pivotal role in the adaptation of bacterial populations, allowing them to rapidly cope with hostile conditions, including the presence of antimicrobial compounds. While the role of SXT/R391 ICEs has been extensively studied over the last two decades, recent studies have highlighted the sporadic involvement of conjugative plasmids of the IncA/C group (ACPs) in genome plasticity and multidrug resistance (MDR) acquisition in V. cholerae [12,13,14,15,16,17,18]. Several reports have associated ACPs with resistance to penicillins, cephalosporins, and carbapenems, conferred by allelic variants of the blaNDM gene [25,26,27,28] These plasmids are frequently detected in food products, foodproducing animals, and environmental samples that likely constitute a large reservoir for their subsequent dissemination to human pathogens [19]. AcaCD was shown to trans-activate excision and dissemination of MDR-conferring Salmonella genomic island 1 (SGI1) and unrelated MGIVmi of Vibrio mimicus (Fig. 1) [20, 21, 29]

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