Induction kinetics of the Staphylococcus aureus cell wall stress stimulon in response to different cell wall active antibiotics.

Induction kinetics of the Staphylococcus aureus cell wall stress stimulon in response to different cell wall active antibiotics.
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DOI:
10.1186/1471-2180-11-16
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发表时间:
2011-01-20
期刊:
影响因子:
4.2
通讯作者:
McCallum N
McCallum N
中科院分区:
生物学3区
文献类型:
--
作者:
Dengler V;Meier PS;Heusser R;Berger-Bächi B;McCallum N

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金黄色葡萄球菌激活保护性细胞壁应激刺激子(CWSS),以响应由几种结构和功能不同的抗生素引起的细胞壁合成抑制或细胞包膜损伤。CWSS诱导由VraSR双组分系统协调,该系统感测由不同细胞壁活性剂触发的未知信号。我们构建了一个高灵敏度的荧光素酶报告基因系统。aureus N315),其检测到非常细微的表达差异以及测量CWSS活性的> 4对数倍变化,以比较具有不同细胞包膜靶标的抗生素的CWSS诱导动力学的浓度依赖性。我们比较了磷霉素、D-环丝氨酸、衣霉素、杆菌肽、黄霉素、万古霉素、替考拉宁、苯唑西林、溶葡萄球菌酶和达托霉素的亚抑制浓度和超抑制浓度的作用。诱导动力学都强烈抗生素和浓度依赖性。大多数抗生素引发了立即的反应,诱导开始在10分钟内,除了衣霉素,D-环丝氨酸和磷霉素,其表现出滞后多达一代诱导开始之前。诱导特性,如CWSS诱导率一旦启动和最大诱导达到,强烈抗生素依赖性。我们观察到特定抗生素浓度对生长的抑制作用与CWSS诱导动力学的相应增加之间存在明确的相关性。VraR的失活使对测试的抗生素的敏感性增加了2至16倍,除了苯唑西林和D-环丝氨酸,在甲氧西林敏感的S.金黄色葡萄球菌菌株背景分析。各种抗生素的诱导能力和CWSS对相应耐药表型的相对重要性之间没有明显的相关性。CWSS诱导曲线对于每种抗生素是独特的。在设计和解释CWSS诱导研究时,应确定并考虑特定抗生素最佳诱导条件中观察到的差异。
Staphylococcus aureus activates a protective cell wall stress stimulon (CWSS) in response to the inhibition of cell wall synthesis or cell envelope damage caused by several structurally and functionally different antibiotics. CWSS induction is coordinated by the VraSR two-component system, which senses an unknown signal triggered by diverse cell wall active agents. We have constructed a highly sensitive luciferase reporter gene system, using the promoter of sas016 (S. aureus N315), which detects very subtle differences in expression as well as measuring > 4 log-fold changes in CWSS activity, to compare the concentration dependence of CWSS induction kinetics of antibiotics with different cell envelope targets. We compared the effects of subinhibitory up to suprainhibitory concentrations of fosfomycin, D-cycloserine, tunicamycin, bacitracin, flavomycin, vancomycin, teicoplanin, oxacillin, lysostaphin and daptomycin. Induction kinetics were both strongly antibiotic- and concentration-dependent. Most antibiotics triggered an immediate response with induction beginning within 10 min, except for tunicamycin, D-cycloserine and fosfomycin which showed lags of up to one generation before induction commenced. Induction characteristics, such as the rate of CWSS induction once initiated and maximal induction reached, were strongly antibiotic dependent. We observed a clear correlation between the inhibitory effects of specific antibiotic concentrations on growth and corresponding increases in CWSS induction kinetics. Inactivation of VraR increased susceptibility to the antibiotics tested from 2- to 16-fold, with the exceptions of oxacillin and D-cycloserine, where no differences were detected in the methicillin susceptible S. aureus strain background analysed. There was no apparent correlation between the induction capacity of the various antibiotics and the relative importance of the CWSS for the corresponding resistance phenotypes. CWSS induction profiles were unique for each antibiotic. Differences observed in optimal induction conditions for specific antibiotics should be determined and taken into account when designing and interpreting CWSS induction studies.
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