title: IncA/C Conjugative Plasmids Mobilize a New Family of Multidrug Resistance Islands in Clinical Vibrio cholerae Non-O1/Non-O139 Isolates from Haiti.
abstract: 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. 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.
  
  
  
  Vibrio cholerae, the causative agent of cholera, remains a global public health threat. Seventh-pandemic V. cholerae acquired multidrug resistance genes primarily through circulation of SXT/R391 integrative and conjugative elements. IncA/C conjugative plasmids have sporadically been reported to mediate antimicrobial resistance in environmental and clinical V. cholerae isolates. Our results showed that while IncA/C plasmids are rare in V. cholerae populations, they play an important yet insidious role by specifically propagating a new family of genomic islands conferring resistance to multiple antibiotics. These results suggest that nonepidemic V. cholerae non-O1/non-O139 strains bearing these genomic islands constitute a reservoir of transmissible resistance genes that can be propagated by IncA/C plasmids to V. cholerae populations in epidemic geographical areas as well to pathogenic species of Enterobacteriaceae We recommend future epidemiological surveys take into account the circulation of these genomic islands.
authors.affiliation: Laboratory of Bacterial Molecular Genetics, Département de Biologie, Faculté des Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada Nicolas.Carraro@USherbrooke.ca Vincent.Burrus@USherbrooke.ca.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Carraro
authors.affiliation: Laboratory of Bacterial Molecular Genetics, Département de Biologie, Faculté des Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Rivard
authors.affiliation: Central Veterinary Institute of Wageningen UR, Lelystad, The Netherlands Maryland Pathogen Research Institute, University of Maryland, College Park, Maryland, USA.
authors.forename: Daniela
authors.initials: D
authors.lastname: Ceccarelli
authors.affiliation: Maryland Pathogen Research Institute, University of Maryland, College Park, Maryland, USA Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA Center for Bioinformatics and Computational Biology, University of Maryland Institute for Advanced Computer Studies (UMIACS), University of Maryland, College Park, Maryland, USA.
authors.forename: Rita R
authors.initials: RR
authors.lastname: Colwell
authors.affiliation: Laboratory of Bacterial Molecular Genetics, Département de Biologie, Faculté des Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada Nicolas.Carraro@USherbrooke.ca Vincent.Burrus@USherbrooke.ca.
authors.forename: Vincent
authors.initials: V
authors.lastname: Burrus
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002771:Cholera / Q000382:microbiology; D003227:Conjugation, Genetic; D004251:DNA Transposable Elements; D024901:Drug Resistance, Multiple, Bacterial; D022761:Gene Transfer, Horizontal; D044404:Genomic Islands; D006205:Haiti; D006801:Humans; D032023:Integrons; D010957:Plasmids; D044163:Vibrio cholerae non-O1 / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification
chemical_list: D000900:Anti-Bacterial Agents; D004251:DNA Transposable Elements