Oxidation-sensing Regulator AbfR Regulates Oxidative Stress Responses, Bacterial Aggregation, and Biofilm Formation in Staphylococcus epidermidis
Oxidation-sensing Regulator AbfR Regulates Oxidative Stress Responses, Bacterial Aggregation, and Biofilm Formation in Staphylococcus epidermidis
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氧化感应调节剂 AbfR 调节表皮葡萄球菌的氧化应激反应、细菌聚集和生物膜形成
DOI：
10.1074/jbc.m112.426205
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发表时间：
2013-02-08
影响因子：
4.8
通讯作者：
Yang, Cai-Guang
中科院分区：
文献类型：
--
作者：
Liu, Xing;Sun, Xiaoxu;Yang, Cai-Guang
表皮葡萄球菌是一种臭名昭著的人类病原体，是与植入式医疗器械相关的感染的主要原因。尽管涉及活性氧的氧化还原调节现在被认为是细菌信号和调节的关键组成部分，但表皮葡萄球菌感知和响应氧化应激的机制在很大程度上仍不清楚。在这里，我们报道了一种新的氧化敏感调节剂，AbfR(聚集和生物膜形成调节剂)。在过氧化氢或过氧化异丙苯介导的氧化应激环境下，abfR基因的表达显著上调。与铜绿假单胞菌OspR类似，AbfR是负自我调节的，在氧化剂存在的情况下与启动子DNA解离。体内和体外分析表明，Cys-13和Cys-116是AbfR氧化形成亚基间二硫键的关键功能残基。我们进一步表明，abfR的缺失会显著诱导过氧化氢或异丙苯氢过氧化氢的抗性，增强细菌聚集，减少生物膜的形成。这些作用是由同一操纵子中紧邻abfR基因下游的SERP2195和gpxA-2的去抑制所介导的。因此，氧化应激可能作为一种信号，通过AbfR调节表皮葡萄球菌的关键毒力特性。
Staphylococcus epidermidis is a notorious human pathogen that is the major cause of infections related to implanted medical devices. Although redox regulation involving reactive oxygen species is now recognized as a critical component of bacterial signaling and regulation, the mechanism by which S. epidermidis senses and responds to oxidative stress remains largely unknown. Here, we report a new oxidation-sensing regulator, AbfR (aggregation and biofilm formation regulator) in S. epidermidis. An environment of oxidative stress mediated by H2O2 or cumene hydroperoxide markedly up-regulates the expression of abfR gene. Similar to Pseudomonas aeruginosa OspR, AbfR is negatively autoregulated and dissociates from promoter DNA in the presence of oxidants. In vivo and in vitro analyses indicate that Cys-13 and Cys-116 are the key functional residues to form an intersubunit disulfide bond upon oxidation in AbfR. We further show that deletion of abfR leads to a significant induction in H2O2 or cumene hydroperoxide resistance, enhanced bacterial aggregation, and reduced biofilm formation. These effects are mediated by derepression of SERP2195 and gpxA-2 that lie immediately downstream of the abfR gene in the same operon. Thus, oxidative stress likely acts as a signal to modulate S. epidermidis key virulence properties through AbfR.