Cyclodepsipeptides produced by actinomycetes inhibit cyclic-peptide-mediated quorum sensing in Gram-positive bacteria
Cyclodepsipeptides produced by actinomycetes inhibit cyclic-peptide-mediated quorum sensing in Gram-positive bacteria
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DOI：
10.1093/femsle/fnv109
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发表时间：
2015-07-01
影响因子：
2.1
通讯作者：
Nakayama, Jiro
中科院分区：
文献类型：
--
作者：
Desouky, Said E.;Shojima, Akane;Nakayama, Jiro
环肽通常用作革兰氏阳性厚壁菌门细菌中的群体感应自诱导剂。这种分子的充分研究的例子是硫内酯和内酯，用于调节一系列的毒力基因的表达，分别在金黄色葡萄球菌的agr系统和粪肠球菌的fsr系统。通过对放线菌培养物提取物的agr/fsr系统活性筛选，鉴定出3种环缩酚肽WS 9326 A、WS 9326 B和Cochinmicin II/III。这些分子已经被称为受体拮抗剂，前两种是速激肽，最后一种是内皮素。WS 9326 A还抑制产气荚膜梭菌中由VirSR双组分系统调节的pfoA的转录。使用荧光标记的自诱导剂（FITC-GBAP）的受体结合试验表明，WS 9326 A和WS 9326 B在该系统中作为受体拮抗剂。此外，离体试验表明，WS 9326 B显著减弱了S.人角膜上皮细胞的金黄色葡萄球菌。这些结果表明，这三种天然环缩肽具有靶向革兰氏阳性病原体的环肽介导的群体感应的治疗潜力。
Cyclic peptides are commonly used as quorum-sensing autoinducers in Gram-positive Firmicutes bacteria. Well-studied examples of such molecules are thiolactone and lactone, used to regulate the expression of a series of virulence genes in the agr system of Staphylococcus aureus and the fsr system of Enterococcus faecalis, respectively. Three cyclodepsipeptides-WS9326A, WS9326B and cochinmicin II/III were identified as a result of screening actinomycetes culture extracts for activity against the agr/fsr system. These molecules are already known as receptor antagonists, the first two for tachykinin and the last one for endothelin. WS9326A also inhibited the transcription of pfoA regulated by the VirSR two-component system in Clostridium perfringens. Receptor-binding assays using a fluorescence-labeled autoinducer (FITC-GBAP) showed that WS9326A and WS9326B act as receptor antagonists in this system. In addition, an ex vivo assay showed that WS9326B substantially attenuated the toxicity of S. aureus for human corneal epithelial cells. These results suggest that these three natural cyclodepsipeptides have therapeutic potential for targeting the cyclic peptide-mediated quorum sensing of Gram-positive pathogens.