Antimicrobial Peptides Activate the Rcs Regulon through the Outer Membrane Lipoprotein RcsF

Antimicrobial Peptides Activate the Rcs Regulon through the Outer Membrane Lipoprotein RcsF
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DOI:
10.1128/jb.00505-10
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发表时间:
2010-10-01
影响因子:
3.2
通讯作者:
Miller, Samuel I.
Miller, Samuel I.
中科院分区:
生物学3区
文献类型:
--
作者:
Farris, Carol;Sanowar, Sarah;Miller, Samuel I.

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肠道沙门氏菌因其环境和传染性生活方式而面临包膜压力。此类应激包括两亲性阳离子抗菌肽 (CAMP),对这些肽的抗性是动物微生物毒力的重要特性。用于感知和响应 CAMP 诱导的包膜应激的细菌机制包括 RcsFCDB 磷酸继电器,它有助于在多粘菌素 B 暴露下存活。 Rcs 磷酸中继包括两种内膜 (IM) 蛋白:RcsC 和 RcsD;响应调节器RcsB;辅助核心调节器 RcsA;和外膜结合脂蛋白,RcsF。 Rcs 调节子的转录激活发生在暴露于 CAMP 的几分钟内以及 CAMP 诱导的膜紊乱的第一个可检测迹象期间。 CAMP 的 Rcs 转录激活需要 RcsF 并保留其两个内部二硫键。 RcsF 重新路由至内膜或其合成为非锚定周质蛋白导致 Rcs 调节子的组成型激活和 RcsCD 依赖性磷酸化。这些发现表明,CAMP 诱导的膜紊乱引起的 RcsFCDB 激活是 Rcs 磷酸继电器的 IM 信号成分的结构或可用性发生变化的结果。
Salmonella enterica species are exposed to envelope stresses due to their environmental and infectious lifestyles. Such stresses include amphipathic cationic antimicrobial peptides (CAMPs), and resistance to these peptides is an important property for microbial virulence for animals. Bacterial mechanisms used to sense and respond to CAMP-induced envelope stress include the RcsFCDB phosphorelay, which contributes to survival from polymyxin B exposure. The Rcs phosphorelay includes two inner membrane (IM) proteins, RcsC and RcsD; the response regulator RcsB; the accessory coregulator RcsA; and an outer membrane bound lipoprotein, RcsF. Transcriptional activation of the Rcs regulon occurred within minutes of exposure to CAMP and during the first detectable signs of CAMP-induced membrane disorder. Rcs transcriptional activation by CAMPs required RcsF and preservation of its two internal disulfide linkages. The rerouting of RcsF to the inner membrane or its synthesis as an unanchored periplasmic protein resulted in constitutive activation of the Rcs regulon and RcsCD-dependent phosphorylation. These findings suggest that RcsFCDB activation in response to CAMP-induced membrane disorder is a result of a change in structure or availability of RcsF to the IM signaling constituents of the Rcs phosphorelay.