Impact of daptomycin resistance on Staphylococcus aureus virulence
Impact of daptomycin resistance on Staphylococcus aureus virulence
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DOI：
10.1080/21505594.2015.1011532
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发表时间：
2015-02-01
期刊：
影响因子：
5.2
通讯作者：
Peleg, Anton Y.
中科院分区：
文献类型：
--
作者：
Cameron, David R.;Mortin, Lawrence I.;Peleg, Anton Y.
金黄色葡萄球菌的达托霉素耐药性（DAP（R））与葡萄球菌致病相关的基因突变有关。使用实验室衍生的一系列DAP暴露菌株，我们显示了在大蜡螟感染模型中增加DAP MIC和降低毒力之间的关系。walK和rpoC的点突变导致毒力的累积降低和DAP MIC的同时增加。mprF的点突变不影响金黄色葡萄球菌的毒力;然而mprF的缺失导致毒力减弱和对DAP的超敏感性。为了验证我们在G.在Mellonella中，我们使用鼠败血症模型证实了从实验室衍生系列中选择的分离株的减毒力。作为一个推论，我们发现临床来源的DAP（R）分离株与其同基因的DAP敏感祖细胞（DAP（S））相比，毒力显著降低。有趣的是，每种临床分离的DAP（R）在体内都是持久的。综合起来，似乎S.金黄色葡萄球菌也改变致病性。
Daptomycin resistance (DAP(R)) in Staphylococcus aureus is associated with mutations in genes that are also implicated in staphylococcal pathogenesis. Using a laboratory-derived series of DAP exposed strains, we showed a relationship between increasing DAP MIC and reduced virulence in a Galleria mellonella infection model. Point mutations in walK and rpoC led to cumulative reductions in virulence and simultaneous increases in DAP MIC. A point mutation to mprF did not impact on S.aureus virulence; however deletion of mprF led to virulence attenuation and hyper-susceptibility to DAP. To validate our findings in G. mellonella, we confirmed the attenuated virulence of select isolates from the laboratory-derived series using a murine septicaemia model. As a corollary, we showed significant virulence reductions for clinically-derived DAP(R) isolates compared to their isogenic, DAP-susceptible progenitors (DAP(S)). Intriguingly, each clinical DAP(R) isolate was persistent in vivo. Taken together, it appears the genetic correlates underlying daptomycin resistance in S. aureus also alter pathogenicity.