title: Coprinuslactone protects the edible mushroom Coprinus comatus against biofilm infections by blocking both quorum-sensing and MurA.
abstract: Pathogens embedded in biofilms are involved in many infections and are very difficult to treat with antibiotics because of higher resistance compared with planktonic cells. Therefore, new approaches for their control are urgently needed. One way to search for biofilm dispersing compounds is to look at defense strategies of organisms exposed to wet environments, which makes them prone to biofilm infections. It is reasonable to assume that mushrooms have developed mechanisms to control biofilms on their sporocarps (fruiting bodies). A preliminary screening for biofilms on sporocarps revealed several species with few or no bacteria on their sporocarps. From the edible mushroom Coprinus comatus where no bacteria on the sporocarp could be detected (3R,4S)-2-methylene-3,4-dihydroxypentanoic acid 1,4-lactone, named coprinuslactone, was isolated. Coprinuslactone interfered with quorum-sensing and dispersed biofilms of Pseudomonas aeruginosa, where it also reduced the formation of the pathogenicity factors pyocyanin and rhamnolipid B. Coprinuslactone also damaged Staphylococcus aureus cells in biofilms at subtoxic concentrations. Furthermore, it inhibited UDP-N-acetylglucosamine enolpyruvyl transferase (MurA), essential for bacterial cell wall synthesis. These two modes of action ensure the inhibition of a broad spectrum of pathogens on the fruiting body but may also be useful for future clinical applications.
authors.affiliation: Chemical Microbiology, Helmholtz Center for Infection Research, Braunschweig, 38124, Germany.
authors.forename: Maira P
authors.initials: MP
authors.lastname: de Carvalho
authors.affiliation: Microbial Interactions and Processes, Helmholtz Center for Infection Research, Braunschweig, 38124, Germany.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Gulotta
authors.affiliation: Chemical Microbiology, Helmholtz Center for Infection Research, Braunschweig, 38124, Germany.
authors.forename: Matheus W
authors.initials: MW
authors.lastname: do Amaral
authors.affiliation: Central Facility for Microscopy, Helmholtz Center for Infection Research, Braunschweig, 38124, Germany.
authors.forename: Heinrich
authors.initials: H
authors.lastname: Lünsdorf
authors.affiliation: Chemical Biology, Helmholtz Center for Infection Research, Braunschweig, 38124, Germany.
authors.forename: Florenz
authors.initials: F
authors.lastname: Sasse
authors.affiliation: Chemical Microbiology, Helmholtz Center for Infection Research, Braunschweig, 38124, Germany.
authors.forename: Wolf-Rainer
authors.initials: WR
authors.lastname: Abraham
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000235:genetics* / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D018441:Biofilms / Q000187:drug effects*; D003302:Coprinus / Q000737:chemistry* / Q000378:metabolism; D048690:Fruiting Bodies, Fungal / Q000737:chemistry / Q000378:metabolism; D006017:Glycolipids / Q000378:metabolism; D007783:Lactones / Q000378:metabolism / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D053038:Quorum Sensing / Q000187:drug effects*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D014675:Vegetables / Q000737:chemistry / Q000378:metabolism / Q000382:microbiology*
chemical_list: D001426:Bacterial Proteins; D006017:Glycolipids; D007783:Lactones; C418382:rhamnolipid; D019883:Alkyl and Aryl Transferases; C022566:UDP-N-acetylglucosamine 1-carboxyvinyltransferase