title: Inhibition of virulence gene expression in Staphylococcus aureus by novel depsipeptides from a marine photobacterium.
abstract: During a global research expedition, more than five hundred marine bacterial strains capable of inhibiting the growth of pathogenic bacteria were collected. The purpose of the present study was to determine if these marine bacteria are also a source of compounds that interfere with the agr quorum sensing system that controls virulence gene expression in Staphylococcus aureus. Using a gene reporter fusion bioassay, we recorded agr interference as enhanced expression of spa, encoding Protein A, concomitantly with reduced expression of hla, encoding α-hemolysin, and rnaIII encoding RNAIII, the effector molecule of agr. A marine Photobacterium produced compounds interfering with agr in S. aureus strain 8325-4, and bioassay-guided fractionation of crude extracts led to the isolation of two novel cyclodepsipeptides, designated solonamide A and B. Northern blot analysis confirmed the agr interfering activity of pure solonamides in both S. aureus strain 8325-4 and the highly virulent, community-acquired strain USA300 (CA-MRSA). To our knowledge, this is the first report of inhibitors of the agr system by a marine bacterium.
authors.affiliation: Center for Microbial Biotechnology, Department of Systems Biology, Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark.
authors.forename: Maria
authors.initials: M
authors.lastname: Mansson
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Life Sciences, University of Copenhagen, DK-1870 Frederiksberg C, Denmark.
authors.forename: Anita
authors.initials: A
authors.lastname: Nielsen
authors.affiliation: Department of Chemistry, Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark.
authors.forename: Louise
authors.initials: L
authors.lastname: Kjærulff
authors.affiliation: Department of Chemistry, Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark.
authors.forename: Charlotte H
authors.initials: CH
authors.lastname: Gotfredsen
authors.affiliation: National Food Institute, Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark.
authors.forename: Matthias
authors.initials: M
authors.lastname: Wietz
authors.affiliation: Department of Veterinary Disease Biology, Faculty of Life Sciences, University of Copenhagen, DK-1870 Frederiksberg C, Denmark.
authors.forename: Hanne
authors.initials: H
authors.lastname: Ingmer
authors.affiliation: National Food Institute, Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark.
authors.forename: Lone
authors.initials: L
authors.lastname: Gram
authors.affiliation: Center for Microbial Biotechnology, Department of Systems Biology, Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark.
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Larsen
mesh_terms: D047630:Depsipeptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D010776:Photobacterium / Q000378:metabolism*; D053038:Quorum Sensing / Q000187:drug effects*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity; D014774:Virulence; D014871:Water Microbiology
chemical_list: D047630:Depsipeptides