Simões Patrícia Martins, Lemriss Hajar, Dumont Yann, Lemriss Sanâa, Rasigade Jean-Philippe, Assant-Trouillet Sophie, Ibrahimi Azeddine, El Kabbaj Saâd, Butin Marine, Laurent Frédéric
Department of Clinical Microbiology, Northern Hospital Group, Hospices Civils de LyonLyon, France; International Centre for Research in Infectious Diseases, Institut National de la Santé et de la Recherche Médicale U1111, University of LyonLyon, France; National Reference Center for Staphylococci, Hospices Civils de LyonLyon, France.
Biotechnology Laboratory (Medbiotech), Medical and Pharmacy School, University Mohammed V de Rabat Rabat, Morocco.
Front Microbiol. 2016 Dec 15;7:1991. doi: 10.3389/fmicb.2016.01991. eCollection 2016.
The multi-resistant clone NRCS-A has recently been described as a major pathogen causing nosocomial, late-onset sepsis (LOS) in preterm neonates worldwide. NRCS-A representatives exhibit an atypical antibiotic resistance profile. Here, the complete closed genome (chromosomal and plasmid sequences) of NRCS-A prototype strain CR01 and the draft genomes of three other clinical NRCS-A strains from Australia, Belgium and the United Kingdom are annotated and compared to available non-NRCS-A genomes. Our goal was to delineate the uniqueness of the NRCS-A clone with respect to antibiotic resistance, virulence factors and mobile genetic elements. We identified 6 antimicrobial resistance genes, all carried by mobile genetic elements. Previously described virulence genes present in the NRCS-A genomes are shared with the six non-NRCS-A genomes. Overall, 63 genes are specific to the NRCS-A lineage, including 28 genes located in the methicillin-resistance cassette SCC. Among the 35 remaining genes, 25 are of unknown function, and 9 correspond to an additional type I restriction modification system ( = 3), a cytosine methylation operon ( = 2), and a cluster of genes related to the biosynthesis of teichoic acids ( = 4). Interestingly, a tenth gene corresponds to a resistance determinant for nisin ( gene), a bacteriocin secreted by potential NRCS-A strain niche competitors in the gut microbiota. The genomic characteristics presented here emphasize the contribution of mobile genetic elements to the emergence of multidrug resistance in the NRCS-A clone. No NRCS-A-specific known virulence determinant was detected, which does not support a role for virulence as a driving force of NRCS-A emergence in NICUs worldwide. However, the presence of a nisin resistance determinant on the NRCS-A chromosome, but not in other strains and most coagulase-negative representatives, might confer a competitive advantage to NRCS-A strains during the early steps of gut colonization in neonates. This suggests that the striking adaptation of NRCS-A to the NICU environment might be related to its specific antimicrobial resistance and also to a possible enhanced ability to challenge competing bacteria in its ecological niche.
多重耐药克隆NRCS-A最近被描述为一种主要病原体，可在全球范围内导致早产儿医院获得性迟发性败血症（LOS）。NRCS-A代表菌株呈现出非典型的抗生素耐药谱。在此，对NRCS-A原型菌株CR01的完整闭合基因组（染色体和质粒序列）以及来自澳大利亚、比利时和英国的其他三株临床NRCS-A菌株的草图基因组进行注释，并与现有的非NRCS-A基因组进行比较。我们的目标是描绘NRCS-A克隆在抗生素耐药性、毒力因子和可移动遗传元件方面的独特性。我们鉴定出6个抗菌耐药基因，均由可移动遗传元件携带。NRCS-A基因组中先前描述的毒力基因与6个非NRCS-A基因组共有。总体而言，63个基因是NRCS-A谱系特有的，其中28个基因位于耐甲氧西林盒式结构SCC中。在其余35个基因中，25个功能未知，9个对应于另外一种I型限制修饰系统（=3）、一个胞嘧啶甲基化操纵子（=2）以及一组与磷壁酸生物合成相关的基因（=4）。有趣的是，第10个基因对应于乳链菌肽的耐药决定因子（nis基因），乳链菌肽是肠道微生物群中潜在的NRCS-A菌株生态位竞争者分泌的一种细菌素。此处呈现的基因组特征强调了可移动遗传元件对NRCS-A克隆中多药耐药性出现的作用。未检测到NRCS-A特异性的已知毒力决定因素，这并不支持毒力作为全球新生儿重症监护病房中NRCS-A出现的驱动力的作用。然而，NRCS-A染色体上存在乳链菌肽耐药决定因子，而其他菌株和大多数凝固酶阴性代表菌株中不存在，这可能在新生儿肠道定植的早期阶段赋予NRCS-A菌株竞争优势。这表明NRCS-A对新生儿重症监护病房环境的显著适应性可能与其特定的抗菌耐药性有关，也可能与其在生态位中挑战竞争细菌的能力增强有关。
