Infection and Immunity Program, Monash Biomedicine Discovery Institute and Department of Microbiology, Monash University, Clayton, Victoria, Australia.
Department of Microbiology and Immunology, The University of Melbourne at The Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
Antimicrob Agents Chemother. 2019 Feb 26;63(3). doi: 10.1128/AAC.01926-18. Print 2019 Mar.
Coagulase-negative staphylococci (CoNS) represent one of the major causes of health care- and medical device-associated infections. Emerging antimicrobial resistance has complicated the treatment of systemic infections caused by CoNS. Here, we describe the prevalence of antimicrobial resistance in clinical CoNS strains from a tertiary care hospital over a 4-year period, and we observed a significant increase in resistance to daptomycin. Notably, accounted for the majority of these daptomycin-resistant (DAP-R) CoNS. To further investigate the mechanisms of daptomycin resistance in CoNS, daptomycin-susceptible clinical strains of and underwent daptomycin exposure to generate DAP-R CoNS mutants. Unlike that seen with , alteration of cell surface charge was not observed in the DAP-R CoNS strains, but biofilm formation was compromised. Whole-genome sequencing analysis of the DAP-R CoNS strains identified single nucleotide polymorphisms (SNPs) in , the essential two-component regulatory system controlling cell wall biogenesis. PCR and sequencing of and from 17 DAP-R CoNS clinical isolates identified seven nonsynonymous mutations. The results were confirmed by the recreation of the SNP in , which resulted in reduced susceptibility to daptomycin and vancomycin. This study highlights the significance of CoNS in evolving daptomycin resistance and showed that is shared among the staphylococcal species and is involved in antibiotic resistance development. Notably, we did not observe mutations in genes responsible for phospholipid biosynthesis or an altered cell surface charge, suggesting that reduced daptomycin susceptibility in CoNS may emerge in a fashion distinct from that in .
凝固酶阴性葡萄球菌（CoNS）是引起医疗保健和医疗器械相关感染的主要原因之一。新兴的抗生素耐药性使 CoNS 引起的全身感染的治疗变得复杂。在这里，我们描述了一家三级医院在 4 年内临床 CoNS 菌株对抗生素耐药性的流行情况，并且观察到对达托霉素的耐药性显著增加。值得注意的是，在这些达托霉素耐药（DAP-R）CoNS 中，占了绝大多数。为了进一步研究 CoNS 对达托霉素耐药的机制，对达托霉素敏感的临床 和 菌株进行了 达托霉素暴露，以产生 DAP-R CoNS 突变体。与 不同，DAP-R CoNS 菌株中未观察到细胞表面电荷的改变，但生物膜形成受到损害。对 DAP-R CoNS 菌株的全基因组测序分析确定了 中控制细胞壁生物合成的必需双组分调节系统的单核苷酸多态性（SNP）。从 17 株 DAP-R CoNS 临床分离株中 和 的 PCR 和测序鉴定出 7 个非同义突变。通过在 中重现 SNP 的结果得到了证实，这导致对达托霉素和万古霉素的敏感性降低。这项研究强调了 CoNS 在产生达托霉素耐药性方面的重要性，并表明 在葡萄球菌种间共享，并参与抗生素耐药性的发展。值得注意的是，我们没有观察到负责磷脂生物合成的基因或细胞表面电荷改变的突变，这表明 CoNS 中达托霉素的低敏感性可能以与 不同的方式出现。
