title: Cyclodepsipeptides produced by actinomycetes inhibit cyclic-peptide-mediated quorum sensing in Gram-positive bacteria.
abstract: 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.
authors.affiliation: Laboratory of Microbial Technology, Division of Applied Molecular Microbiology and Biomass Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan Department of Botany and Microbiology, Faculty of Science, Al-azhar University, 11884 Nasr, Cairo, Egypt.
authors.forename: Said E
authors.initials: SE
authors.lastname: Desouky
authors.affiliation: Laboratory of Microbial Technology, Division of Applied Molecular Microbiology and Biomass Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan.
authors.forename: Akane
authors.initials: A
authors.lastname: Shojima
authors.affiliation: Laboratory of Microbial Technology, Division of Applied Molecular Microbiology and Biomass Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan.
authors.forename: Ravindra Pal
authors.initials: RP
authors.lastname: Singh
authors.affiliation: Laboratory of Microbial Technology, Division of Applied Molecular Microbiology and Biomass Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan.
authors.forename: Takahisa
authors.initials: T
authors.lastname: Matsufuji
authors.affiliation: Biotechnology Research Center, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Igarashi
authors.affiliation: Department of Ophthalmology, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791-0295, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Suntory Foundation for Life Sciences, Bioorganic Research Institute, 1-1-1 Wakayamadai, Shimamoto-cho, Mishima-gun, Osaka 618-8503, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Yamagaki
authors.affiliation: Laboratory of Microbial Technology, Division of Applied Molecular Microbiology and Biomass Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan.
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Okubo
authors.affiliation: Department of Bacteriology, University of Kanazawa, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8203, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Ohtani
authors.affiliation: Laboratory of Microbial Technology, Division of Applied Molecular Microbiology and Biomass Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan Laboratory of Functional Food Design, Department of Functional Metabolic Design, Bio-Architecture Center, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sonomoto
authors.affiliation: Laboratory of Microbial Technology, Division of Applied Molecular Microbiology and Biomass Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan nakayama@agr.kyushu-u.ac.jp.
authors.forename: Jiro
authors.initials: J
authors.lastname: Nakayama
mesh_terms: D039903:Actinobacteria / Q000737:chemistry / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics; D001427:Bacterial Toxins / Q000235:genetics; D002461:Cell Line, Transformed; D003016:Clostridium perfringens / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D003315:Cornea / Q000166:cytology / Q000382:microbiology; D047630:Depsipeptides / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D013293:Enterococcus faecalis / Q000187:drug effects / Q000502:physiology; D006094:Gram-Positive Bacteria / Q000187:drug effects* / Q000502:physiology; D006460:Hemolysin Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007783:Lactones / Q000302:isolation & purification / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D053038:Quorum Sensing / Q000187:drug effects*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000472:pathogenicity / Q000502:physiology; D014774:Virulence / Q000187:drug effects
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D047630:Depsipeptides; D006460:Hemolysin Proteins; D007783:Lactones; D010456:Peptides, Cyclic; C076469:WS 9326A; C078835:cochinmicin II; C020452:Clostridium perfringens theta-toxin
keywords: Enterococcus faecalis; Staphylococcus aureus; agr system; cyclodepsipeptide; fsr system; quorum sensing inhibitor