Clonal relatedness is a predictor of spontaneous multidrug efflux pump gene overexpression in Staphylococcus aureus.
Clonal relatedness is a predictor of spontaneous multidrug efflux pump gene overexpression in Staphylococcus aureus.
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DOI：
10.1016/j.ijantimicag.2014.11.007
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发表时间：
2015-05
影响因子：
10.8
通讯作者：
B. Schindler;P. Jacinto;J. A. Buensalido;S. M. Seo;G. Kaatz
中科院分区：
文献类型：
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作者：
B. Schindler;P. Jacinto;J. A. Buensalido;S. M. Seo;G. Kaatz
编码多药耐药外排泵(MDR-EPs)的基因表达增加与金黄色葡萄球菌的抗菌剂和杀菌剂耐药性有关。先前已发现nAoverase表达与Spat型t002甲氧西林耐药之间的关联。金黄色葡萄球菌(MRSA)，以及mepA过度表达与t008型甲氧西林敏感性之间类似但较弱的关联。临床分离株中的金黄色葡萄球菌(MSSA)提示克隆性传播。相关菌株也可能容易发生突变，导致特定的MDR-EP基因过度表达。将非MDR-EP高表达的临床分离株暴露于杀菌剂和染料可以选择MDR-EP高表达的突变株。spattype t002和t008分离株分别以多位点测序分型序列类型(STS)5和8为主。在这项研究中，代表ST5和ST8的非MDR-EP基因过表达的临床分离株(MRSA和MSSA)被单次暴露于溴化乙锭(EtBR)，以筛选EtBR抗性突变株。突变体之间的活性EtBR转运的测量被用来证明外排熟练的表型。应用定量逆转录聚合酶链式反应发现，无论对甲氧西林敏感与否，ST5和ST8亲本菌株的EtBR抗性突变株分别高表达mepA(100%)和mdeA(83%)。克隆性谱系和MDR-EP基因过度表达之间的关系与先前观察到的不同，表明后者是由于外排熟练的菌株的克隆性传播所致。体外选择的相关菌株的突变体倾向于过度表达相同的MDR-EP基因，这表明存在一致的突变过程。
Increased expression of genes encoding multidrug resistance efflux pumps (MDR-EPs) contributes to antimicrobial agent and biocide resistance inStaphylococcus aureus. Previously identified associations betweennorAoverexpression andspatype t002 meticillin-resistantS. aureus(MRSA), and a similar yet weaker association betweenmepAoverexpression and type t008 meticillin-susceptibleS. aureus(MSSA), in clinical isolates are suggestive of clonal dissemination. It is also possible that related strains are prone to mutations resulting in overexpression of specific MDR-EP genes. Exposure of non-MDR-EP-overexpressing clinical isolates to biocides and dyes can select for MDR-EP-overexpressing mutants.spatypes t002 and t008 isolates are predominated by multilocus sequencing typing sequence types (STs) 5 and 8, respectively. In this study, non-MDR-EP gene-overexpressing clinical isolates (MRSA and MSSA) representing ST5 and ST8 were subjected to single exposures of ethidium bromide (EtBr) to select for EtBr-resistant mutants. Measurements of active EtBr transport among mutants were used to demonstrate an efflux-proficient phenotype. Using quantitative reverse-transcription PCR, it was found that EtBr-resistant mutants of ST5 and ST8 parental strains predominantly overexpressedmepA(100%) andmdeA(83%), respectively, regardless of meticillin sensitivity. Associations between clonal lineage and MDR-EP gene overexpression differed from those previously observed and suggest the latter is due to clonal spread of efflux-proficient strains. The predilection of in vitro-selected mutants of related strains to overexpress the same MDR-EP gene indicates the presence of a consistent mutational process.