Remodeling of pSK1 Family Plasmids and Enhanced Chlorhexidine Tolerance in a Dominant Hospital Lineage of Methicillin-Resistant Staphylococcus aureus
Remodeling of pSK1 Family Plasmids and Enhanced Chlorhexidine Tolerance in a Dominant Hospital Lineage of Methicillin-Resistant Staphylococcus aureus
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DOI：
10.1128/aac.02356-18
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发表时间：
2019-05-01
影响因子：
4.9
通讯作者：
Stinear, Timothy P.
中科院分区：
文献类型：
--
作者：
Baines, Sarah L.;Jensen, Slade O.;Stinear, Timothy P.
金黄色葡萄球菌是一种重要的人类病原体，其进化和适应部分受到移动遗传元件（MGE）的影响，促进了广泛的抗菌药物耐药性在全球的传播。然而，我们对 MGE 进化动态的理解，特别是多药耐药 (MDR) 质粒结构的变化如何影响重要的葡萄球菌表型，尚不完整。在这里，我们对 32 年来收集的 212 个耐甲氧西林金黄色葡萄球菌 (MRSA) 序列类型 239 (ST239) 分离株进行了群体和功能基因组学研究，以探索 MDR 质粒 pSK1 家族的进化，说明这些质粒如何与这种持久性 MRSA 谱系共同进化并对其成功适应作出贡献。利用完整的基因组和时间系统基因组学，我们重建了 pSK1 家族谱系自 20 世纪 70 年代末出现以来的进化过程，发现出现了多种结构变异。质粒的维持和稳定性与 IS256 和 IS257 介导的染色体整合和质粒复制机制的破坏有关。将基因组比较与庆大霉素、甲氧苄啶和氯己定的表型敏感性数据相叠加，发现 pSK1 通过两种机制增强 ST239 MRSA 分离株的耐药性：(i) 获得质粒传播的耐药机制，增加庆大霉素耐药率并降低氯己定敏感性；(ii) 耐药性的变化 质粒构型与氯己定耐受性的进一步增强有关。虽然增强耐受性的确切机制仍然难以捉摸，但这项研究发现了 ST239 MRSA 对杀菌剂的潜在进化反应，其中之一可能有助于该谱系在医疗保健机构内的持续存在和适应。
Staphylococcus aureus is a significant human pathogen whose evolution and adaptation have been shaped in part by mobile genetic elements (MGEs), facilitating the global spread of extensive antimicrobial resistance. However, our understanding of the evolutionary dynamics surrounding MGEs, in particular, how changes in the structure of multidrug resistance (MDR) plasmids may influence important staphylococcal phenotypes, is incomplete. Here, we undertook a population and functional genomics study of 212 methicillin-resistant S. aureus (MRSA) sequence type 239 (ST239) isolates collected over 32 years to explore the evolution of the pSK1 family of MDR plasmids, illustrating how these plasmids have coevolved with and contributed to the successful adaptation of this persistent MRSA lineage. Using complete genomes and temporal phylogenomics, we reconstructed the evolution of the pSK1 family lineage from its emergence in the late 1970s and found that multiple structural variants have arisen. Plasmid maintenance and stability were linked to IS256-and IS257-mediated chromosomal integration and disruption of the plasmid replication machinery. Overlaying genomic comparisons with phenotypic susceptibility data for gentamicin, trimethoprim, and chlorhexidine, it appeared that pSK1 has contributed to enhanced resistance in ST239 MRSA isolates through two mechanisms: (i) acquisition of plasmid-borne resistance mechanisms increasing the rates of gentamicin resistance and reduced chlorhexidine susceptibility and (ii) changes in the plasmid configuration linked with further enhancement of chlorhexidine tolerance. While the exact mechanism of enhanced tolerance remains elusive, this research has uncovered a potential evolutionary response of ST239 MRSA to biocides, one of which may contribute to the ongoing persistence and adaptation of this lineage within health care institutions.