title: Ambuic acid inhibits the biosynthesis of cyclic peptide quormones in gram-positive bacteria.
abstract: Quorum sensing is a cell-density-dependent regulatory system in gram-positive bacteria and is often regulated by cyclic peptides called "quormones," which function as extracellular communication signals. With an aim to discover an antipathogenic agent targeting quorum sensing in gram-positive bacteria, we screened 153 samples of fungal butanol extracts with the guidance of the inhibition of quorum-sensing-mediated gelatinase production in Enterococcus faecalis. Following the screenings, we found that ambuic acid, a known secondary fungal metabolite, inhibited the quorum-sensing-mediated gelatinase production without influencing the growth of E. faecalis. We further demonstrated that ambuic acid targeted the biosynthesis of a cyclic peptide quormone called gelatinase biosynthesis-activating pheromone. Furthermore, ambuic acid also inhibited the biosynthesis of the cyclic peptide quormones of Staphylococcus aureus and Listeria innocua. These results suggest the potential use of ambuic acid as a lead compound of antipathogenic drugs that target the quorum-sensing-mediated virulence expression of gram-positive bacteria.
authors.affiliation: Department of Bioscience and Biotechnology, Graduate School, Kyushu University, Hakozaki, Higashi-ku, Fukuoka, Japan. nakayama@agr.kyushu-u.ac.jp
authors.forename: Jiro
authors.initials: J
authors.lastname: Nakayama
authors.forename: Yumi
authors.initials: Y
authors.lastname: Uemura
authors.forename: Kenzo
authors.initials: K
authors.lastname: Nishiguchi
authors.forename: Norito
authors.initials: N
authors.lastname: Yoshimura
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Igarashi
authors.forename: Kenji
authors.initials: K
authors.lastname: Sonomoto
mesh_terms: D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics; D002851:Chromatography, High Pressure Liquid; D003512:Cyclohexanones / Q000302:isolation & purification / Q000494:pharmacology*; D013293:Enterococcus faecalis / Q000187:drug effects / Q000378:metabolism; D018093:Gelatinases / Q000096:biosynthesis; D006094:Gram-Positive Bacteria / Q000187:drug effects* / Q000378:metabolism*; D006460:Hemolysin Proteins / Q000096:biosynthesis / Q000235:genetics; D007783:Lactones; D008087:Listeria / Q000187:drug effects / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010456:Peptides, Cyclic / Q000096:biosynthesis* / Q000235:genetics; D053038:Quorum Sensing / Q000187:drug effects*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000378:metabolism; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics
chemical_list: C095698:Agr protein, Staphylococcus aureus; D001426:Bacterial Proteins; D003512:Cyclohexanones; D006460:Hemolysin Proteins; D007783:Lactones; D010456:Peptides, Cyclic; D015534:Trans-Activators; C429363:ambuic acid; C438382:gelatinase biosynthesis-activating pheromone; D018093:Gelatinases