Carraro Nicolas, Rivard Nicolas, Ceccarelli Daniela, Colwell Rita R, Burrus Vincent
Laboratory of Bacterial Molecular Genetics, Département de Biologie, Faculté des Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada
Laboratory of Bacterial Molecular Genetics, Département de Biologie, Faculté des Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
mBio. 2016 Jul 19;7(4):e00509-16. doi: 10.1128/mBio.00509-16.
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.
移动遗传元件在细菌群体的适应性中起关键作用，使它们能够迅速应对恶劣条件，包括抗菌化合物的存在。IncA/C接合质粒（ACPs）是在多种致病性肠杆菌科物种中传播多药耐药基因的有效载体。在霍乱弧菌（腹泻病霍乱的病原体）中偶尔有关于ACPs的报道。控制ACP移动性的调控网络最终取决于主激活因子AcaCD对多个ACP携带的操纵子的转录激活。除了ACP接合作用外，最近还发现AcaCD可激活位于沙门氏菌基因组岛1（SGI1）中的基因的表达。在此，我们描述了MGIVchHai6，这是一个新的且不相关的可移动基因组岛（MGI），整合到霍乱弧菌HC - 36A1染色体I中trmE的3'末端，该菌株是2010年从海地分离出的一株非O1/非O139多药耐药临床菌株。MGIVchHai6包含一个汞抗性转座子和一个与SGI1中的整合子In104样多药耐药元件相似的元件。我们表明MGIVchHai6以AcaCD依赖的方式从染色体上切除，并由ACPs进行转移。获得MGIVchHai6会赋予对β - 内酰胺类、磺胺甲恶唑、四环素、氯霉素、甲氧苄啶以及链霉素/壮观霉素的抗性。计算机分析表明，MGIVchHai6样元件存在于从印度次大陆以及北美洲和南美洲分离出的几种环境和临床霍乱弧菌菌株中，包括来自海地的所有非O1/非O139临床分离株。
霍乱弧菌作为霍乱的病原体，仍然是全球公共卫生威胁。第七次霍乱大流行的霍乱弧菌主要通过SXT/R391整合和接合元件的传播获得多药耐药基因。偶尔有报道称IncA/C接合质粒在环境和临床霍乱弧菌分离株中介导抗菌抗性。我们的结果表明，虽然IncA/C质粒在霍乱弧菌群体中很少见，但它们通过特异性传播一个赋予多种抗生素抗性的新基因组岛家族发挥着重要但隐蔽的作用。这些结果表明，携带这些基因组岛的非流行霍乱弧菌非O1/非O139菌株构成了一个可传播抗性基因的储存库，这些基因可通过IncA/C质粒传播到流行地理区域的霍乱弧菌群体以及肠杆菌科的致病物种中。我们建议未来的流行病学调查考虑这些基因组岛的传播情况。
