Drivers of methicillin-resistant Staphylococcus aureus (MRSA) lineage replacement in China.
Drivers of methicillin-resistant Staphylococcus aureus (MRSA) lineage replacement in China.
复制标题
DOI：
10.1186/s13073-021-00992-x
复制
发表时间：
2021-10-28
期刊：
影响因子：
12.3
通讯作者：
Balloux F
中科院分区：
文献类型：
--
作者：
Chen H;Yin Y;van Dorp L;Shaw LP;Gao H;Acman M;Yuan J;Chen F;Sun S;Wang X;Li S;Zhang Y;Farrer RA;Wang H;Balloux F
耐甲氧西林金黄色葡萄球菌（MRSA）是一种主要的医院病原体，分为谱系称为序列型（ST）。自20世纪50年代以来，ST的连续浪潮已经出现，并取代了以前占主导地位的血统。自2013年以来，中国一直发生这样的事件，包括ST 59在内的社区相关（CA-MRSA）菌株在很大程度上取代了之前占主导地位的医疗保健相关（HA-MRSA）ST 239。我们以前表明，ST 59菌株往往具有竞争优势，在生长实验对ST 239。然而，这种替换事件的潜在基因组和表型驱动因素尚不清楚。在这里，我们使用1994年至2016年期间在中国医院收集的204株ST 239和ST 59分离株的全基因组测序数据调查了ST 239的替代。我们重建了每个ST的进化历史，并考虑了ST 59取代ST 239的两个非互斥假设：抗菌素耐药性（AMR）特征和/或通过生物膜形成在环境中定植和持续存在的能力。我们还研究了ST之间与更高毒力相关的溶细胞活性的差异。我们进行了关联研究，使用的存在和不存在的辅助毒力基因。ST 59分离株携带的AMR基因比ST 239少，并且没有显示出向更高AMR进化的证据。总体而言，ST 59的生物膜产量略高，但这种影响在亚系中并不一致，因此不太可能是替代的唯一驱动因素。与先前在CA-MRSA ST中观察到的更高毒力一致，我们观察到ST 59分离株表现出比ST 239分离株显著更高的细胞溶解活性，尽管携带平均更少的推定毒力基因。我们的关联研究确定了趋化性抑制蛋白（chp）作为一个强有力的候选人参与增加的毒力潜力的ST 59。我们通过创建Δchp敲除突变体，实验验证了chp在增加ST 59毒力潜力中的作用，证实ST 59可以携带chp，而不会对适应性产生可测量的影响。我们的研究结果表明，在中国，ST 239正在被ST 59取代，这与较高的AMR携带率或生物膜产生无关。然而，ST 59流行率的增加令人担忧，因为它与更高的毒力潜力有关，并得到了chp基因携带的帮助。在线版本包含补充材料，可通过10.1186/s13073-021-00992-x获得。
Methicillin-resistant Staphylococcus aureus (MRSA) is a major nosocomial pathogen subdivided into lineages termed sequence types (STs). Since the 1950s, successive waves of STs have appeared and replaced previously dominant lineages. One such event has been occurring in China since 2013, with community-associated (CA-MRSA) strains including ST59 largely replacing the previously dominant healthcare-associated (HA-MRSA) ST239. We previously showed that ST59 isolates tend to have a competitive advantage in growth experiments against ST239. However, the underlying genomic and phenotypic drivers of this replacement event are unclear. Here, we investigated the replacement of ST239 using whole-genome sequencing data from 204 ST239 and ST59 isolates collected in Chinese hospitals between 1994 and 2016. We reconstructed the evolutionary history of each ST and considered two non-mutually exclusive hypotheses for ST59 replacing ST239: antimicrobial resistance (AMR) profile and/or ability to colonise and persist in the environment through biofilm formation. We also investigated the differences in cytolytic activity, linked to higher virulence, between STs. We performed an association study using the presence and absence of accessory virulence genes. ST59 isolates carried fewer AMR genes than ST239 and showed no evidence of evolving towards higher AMR. Biofilm production was marginally higher in ST59 overall, though this effect was not consistent across sub-lineages so is unlikely to be a sole driver of replacement. Consistent with previous observations of higher virulence in CA-MRSA STs, we observed that ST59 isolates exhibit significantly higher cytolytic activity than ST239 isolates, despite carrying on average fewer putative virulence genes. Our association study identified the chemotaxis inhibitory protein (chp) as a strong candidate for involvement in the increased virulence potential of ST59. We experimentally validated the role of chp in increasing the virulence potential of ST59 by creating Δchp knockout mutants, confirming that ST59 can carry chp without a measurable impact on fitness. Our results suggest that the ongoing replacement of ST239 by ST59 in China is not associated to higher AMR carriage or biofilm production. However, the increase in ST59 prevalence is concerning since it is linked to a higher potential for virulence, aided by the carriage of the chp gene. The online version contains supplementary material available at 10.1186/s13073-021-00992-x.
登录
查看更多内容
影响因子：
3.4
作者：
Bouckaert RR;Drummond AJ
通讯作者：
Drummond AJ
影响因子：
6.4
作者：
Chen, Hongbin;Yin, Yuyao;Wang, Hui
通讯作者：
Wang, Hui
DOI：
10.1007/s10096-016-2663-3
发表时间：
2016-08-01
影响因子：
4.5
作者：
Blomfeldt, A.;Aamot, H. V.;Bjornholt, J. V.
通讯作者：
Bjornholt, J. V.
影响因子：
6.4
作者：
Gill JL;Hedge J;Wilson DJ;MacLean RC
通讯作者：
MacLean RC
影响因子：
1.7
作者：
Bankevich, Anton;Nurk, Sergey;Pevzner, Pavel A.
通讯作者：
Pevzner, Pavel A.