Methicillin-resistant <i>Staphylococcus aureus</i> in China: a multicentre longitudinal study and whole-genome sequencing

The aim of this study was to investigate the genomic epidemiology of MRSA in China to identify predominant lineages and their associated genomic and phenotypic characteristics. In this study, we conducted whole-genome sequencing on 565 MRSA isolates from 7 provinces and municipalities of China between 2014 and 2020. MRSA isolates were subjected to MLST, <i>spa</i> typing, SCC<i>mec</i> typing, analysis of virulence determinants and antimicrobial susceptibility testing. Among 565 MRSA isolates tested, clonal complex (CC) 59 (31.2%), CC5 (23.4%) and CC8 (13.63%) were the major lineages, and the clonal structure was dominated by ST59-t437-IV (14.9%), ST239-t030-III (6.4%) and ST5-t2460-II (6.0%), respectively. Of note, CC8, the predominant lineage in 2014–2015, was replaced by CC59 after 2016. Interestingly, the extension and unstable structure of the CC5 population was observed, with ST5-t311-II, ST764-t1084-II, ST5-t2460-II and ST764-t002-II existing complex competition. Further analysis revealed that virulence determinant profiles and antibiograms were closely associated with the clonal lineage. The CC59 MRSA was less resistant to most tested antimicrobials and carried fewer resistance determinants. But rifampicin resistance and mupirocin resistance were closely linked with CC8 and CC5, respectively. MRSA isolates conservatively carried multiple virulence genes involved in various functions. PVL encoding genes were more common in ST338, CC30, CC398, ST8 and CC22, while <i>tsst</i>-1 was associated with ST5. In conclusion, the community-associated CC59-ST59-t437-IV lineage was predominant in China, with diverse clonal isolates alternately circulating in various geographical locations. Our study highlights the need for MRSA surveillance in China to monitor changes in MRSA epidemiology.

本研究旨在探究中国耐甲氧西林金黄色葡萄球菌（Methicillin-resistant Staphylococcus aureus, MRSA）的基因组流行病学特征，以明确其优势克隆谱系及其相关基因组与表型特性。本研究对2014年至2020年间采集自中国7个省份及直辖市的565株MRSA分离株完成了全基因组测序。对所有受试MRSA分离株依次开展了多位点序列分型（Multilocus Sequence Typing, MLST）、spa分型、葡萄球菌染色体盒式mec元素（Staphylococcal Cassette Chromosome mec, SCCmec）分型、毒力决定因子分析以及抗菌药物敏感性试验。

在565株受试MRSA分离株中，克隆复合群（Clonal Complex, CC）59（31.2%）、CC5（23.4%）与CC8（13.63%）为主要流行谱系，克隆结构以ST59-t437-IV（14.9%）、ST239-t030-III（6.4%）及ST5-t2460-II（6.0%）为主导。值得注意的是，作为2014-2015年的优势谱系，CC8在2016年后被CC59取代。有趣的是，研究观察到CC5种群呈现扩增且结构不稳定的特征，ST5-t311-II、ST764-t1084-II、ST5-t2460-II与ST764-t002-II之间存在复杂的竞争关系。

进一步分析显示，毒力决定因子谱与抗菌药物耐药谱均与克隆谱系密切相关。CC59型MRSA对多数受试抗菌药物的耐药性更低，且携带的耐药决定因子更少。不过，利福平耐药与莫匹罗星耐药分别与CC8和CC5紧密关联。MRSA分离株普遍携带多种参与不同生理功能的毒力基因。杀白细胞毒素（Panton-Valentine Leukocidin, PVL）编码基因在ST338、CC30、CC398、ST8及CC22中更为常见，而毒性休克综合征毒素-1（tsst-1）则与ST5相关。

综上，社区获得性CC59-ST59-t437-IV谱系是中国地区的优势MRSA克隆谱系，多样的克隆分离株在不同地理区域交替流行。本研究强调，中国需加强MRSA监测工作，以持续追踪MRSA流行病学的变化态势。