Cyclodepsipeptides produced by actinomycetes inhibit cyclic-peptide-mediated quorum sensing in Gram-positive bacteria

被引:35
作者
Desouky, Said E. [1 ,2 ]
Shojima, Akane [1 ]
Singh, Ravindra Pal [1 ]
Matsufuji, Takahisa [1 ]
Igarashi, Yasuhiro [3 ]
Suzuki, Takashi [4 ]
Yamagaki, Tohru [5 ]
Okubo, Ken-ichi [1 ]
Ohtani, Kaori [6 ]
Sonomoto, Kenji [1 ,7 ]
Nakayama, Jiro [1 ]
机构
[1] Kyushu Univ, Lab Microbial Technol, Div Appl Mol Microbiol & Biomass Chem, Dept Biosci & Biotechnol,Fac Agr,Grad Sch,Higashi, Fukuoka 8128581, Japan
[2] Al Azhar Univ, Dept Bot & Microbiol, Fac Sci, Cairo 11884, Egypt
[3] Toyama Prefectural Univ, Biotechnol Res Ctr, Imizu, Toyama 9390398, Japan
[4] Ehime Univ, Dept Ophthalmol, Grad Sch Med, Toon, Ehime 7910295, Japan
[5] Suntory Fdn Life Sci, Bioorgan Res Inst, Shimamoto, Osaka 6188503, Japan
[6] Kanazawa Univ, Dept Bacteriol, Kanazawa, Ishikawa 9208203, Japan
[7] Kyushu Univ, Lab Funct Food Design, Dept Funct Metab Design, Bioarchitecture Ctr,Higashi Ku, Fukuoka 8128581, Japan
基金
日本学术振兴会;
关键词
quorum sensing inhibitor; cyclodepsipeptide; agr system; fsr system; Enterococcus faecalis; Staphylococcus aureus; BIOSYNTHESIS-ACTIVATING PHEROMONE; STAPHYLOCOCCUS-AUREUS VIRULENCE; TO-CELL COMMUNICATION; ENDOTHELIN ANTAGONISTS; TOXIN PRODUCTION; GENE-EXPRESSION; MICROBISPORA SP; AGR; COCHINMICINS; INTERFERENCE;
D O I
10.1093/femsle/fnv109
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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.
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页数:9
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