Effects of subinhibitory concentrations of antibiotics on virulence factor expression by community-acquired methicillin-resistant Staphylococcus aureus
Effects of subinhibitory concentrations of antibiotics on virulence factor expression by community-acquired methicillin-resistant Staphylococcus aureus
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DOI：
10.1093/jac/dkt073
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发表时间：
2013-07-01
影响因子：
5.2
通讯作者：
Dumitrescu, Oana
中科院分区：
文献类型：
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作者：
Otto, Marie Pierre;Martin, Emilie;Dumitrescu, Oana
检查亚抑制浓度的影响本研究旨在探讨抗葡萄球菌药物对社区获得性耐甲氧西林金黄色葡萄球菌（CA-MRSA）的PantonValentine杀白细胞素（PVL）、溶血素（Hla）和蛋白A（SpA）表达的影响。5种抗生素（克林霉素、达托霉素、利奈唑胺、替加环素和万古霉素）的1/8、1/4和1/2 MIC。孵育4和6小时后，将培养物沉淀用于相对定量RTPCR，使用pvl、hla、spa和gyrB特异性引物。使用特异性ELISA测量上清液（对于PVL和Hla）和细胞团（对于SpA）中的PVL、Hla和SpA浓度。对于所有测试的菌株，克林霉素和利奈唑胺显著降低PVL和SpA的mRNA水平。替加环素还分别降低了3/5和4/5测试菌株的PVL和SpA mRNA水平，而达托霉素和万古霉素没有显著影响。PVL和SpA定量证实了克林霉素对PVL和SpA产生的浓度依赖性抑制，利奈唑胺和替加环素的抑制程度较低。只有克林霉素降低Hla mRNA表达，而利奈唑胺，替加环素和达托霉素显示异质性菌株依赖性结果，万古霉素没有显着影响。Hla水平分析显示克林霉素对Hla释放的浓度依赖性抑制作用强于利奈唑胺。亚MIC对毒力表达的影响取决于抗生素和毒力因子。克林霉素和利奈唑胺一致抑制CA-MRSA不同毒力因子的表达，而替加环素特异性抑制PVL表达。达托霉素和万古霉素在这些浓度下似乎没有显著影响。
To examine the effect of subinhibitory concentrations (sub-MICs) of antistaphylococcal drugs on PantonValentine leucocidin (PVL), -haemolysin (Hla) and protein A (SpA) expression by community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA).Five clinical isolates representing the main worldwide CA-MRSA clones were grown with sub-MICs (1/8, 1/4 and 1/2 MIC) of five antibiotics (clindamycin, daptomycin, linezolid, tigecycline and vancomycin). After 4 and 6 h of incubation, culture pellets were used for relative quantitative RTPCR with primers specific for pvl, hla, spa and gyrB. The PVL, Hla and SpA concentrations were measured in the supernatant (for PVL and Hla) and in the cell pellet (for SpA) using specific ELISAs.For all strains tested, clindamycin and linezolid dramatically reduced mRNA levels of PVL and SpA. Tigecycline also decreased the PVL and SpA mRNA levels of 3/5 and 4/5 strains tested, respectively, whereas daptomycin and vancomycin had no significant effect. PVL and SpA quantification confirmed the concentration-dependent inhibition of PVL and SpA production by clindamycin and, to a lesser extent, by linezolid and tigecycline. Only clindamycin decreased Hla mRNA expression, whereas linezolid, tigecycline and daptomycin showed heterogeneous strain-dependent results, and vancomycin had no significant effect. Analysis of the Hla level revealed a stronger concentration-dependent inhibition of Hla release by clindamycin than by linezolid.The effect of sub-MICs on virulence expression depended on the antibiotic and the virulence factor. Clindamycin and linezolid consistently suppressed the expression of different virulence factors by CA-MRSA, whereas tigecycline specifically suppressed PVL expression. Daptomycin and vancomycin seem to have no significant effects at these concentrations.