Rationale design of quorum-quenching peptides that target the VirSR system of Clostridium perfringens
Rationale design of quorum-quenching peptides that target the VirSR system of Clostridium perfringens
复制标题
针对产气荚膜梭菌 VirSR 系统的群体淬灭肽的设计原理
DOI：
10.1093/femsle/fnv188
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发表时间：
2015
影响因子：
2.1
通讯作者：
Nakayama
中科院分区：
文献类型：
--
作者：
Singh RP;Okubo K;Ohtani K;Adachi K;Sonomoto K;Nakayama
在产气荚膜梭菌中，5元硫代内酯多肽作为自身诱导肽(AIPCP)激活VirSR二组分信号转导系统，进而控制编码多种毒素的基因的表达，包括α，θ和κ。开发针对强毒C株的抗病原剂。根据AIPCp上的构效关系(SAR)数据，合理设计了产气孔菌、群体猝灭多肽。AIPCp的丙氨酸扫描研究表明，Trp3和Phe4分别参与受体的结合和激活。在此基础上，我们设计了两种不同作用模式的群体猝灭多肽：Z-AIPCp-L2A/T5A(部分激动剂)和Z-AIPCp-F4A/T5S(部分拮抗剂)。两种多肽均显著抑制θ毒素基因(PFOA)在OFC强毒株中的转录。其IC50分别为0.32和0.72μM。
InClostridium perfringens, a 5-membered thiolactone peptide acts as an autoinducing peptide (AIPCp) to activate the VirSR two-component signal transduction system, which in turn controls the expression of genes encoding multiple toxins, including α, θ and κ. To develop anti-pathogenic agents against virulentC. perfringens, quorum-quenching peptides were rationally designed based on the structure–activity relationship (SAR) data on AIPCp. Alanine scanning study of AIPCpsuggested that Trp3and Phe4are involved in receptor binding and activation, respectively. On the basis of the SAR, we designed two quorum-quenching peptides with different modes of action: Z-AIPCp-L2A/T5A (partial agonist) and Z-AIPCp-F4A/T5S (partial antagonist). Both peptides significantly attenuated transcription of θ toxin gene (pfoA) in a virulent strain ofC. perfringenswith IC50= 0.32 and 0.72 μM, respectively.