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Inhibition of Virulence Gene Expression in Staphylococcus aureus by Novel Depsipeptides from a Marine Photobacterium
Center for Microbial Biotechnology, Department of Systems Biology, Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark
Department of Veterinary Disease Biology, Faculty of Life Sciences, University of Copenhagen, DK-1870 Frederiksberg C, Denmark
Department of Chemistry, Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark
National Food Institute, Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark
* Author to whom correspondence should be addressed.
Received: 22 September 2011; in revised form: 22 November 2011 / Accepted: 30 November 2011 / Published: 7 December 2011
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.
Keywords: Photobacterium; Vibrionaceae; antivirulence; quorum sensing inhibition; agr
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Mansson, M.; Nielsen, A.; Kjærulff, L.; Gotfredsen, C.H.; Wietz, M.; Ingmer, H.; Gram, L.; Larsen, T.O. Inhibition of Virulence Gene Expression in Staphylococcus aureus by Novel Depsipeptides from a Marine Photobacterium. Mar. Drugs 2011, 9, 2537-2552.
Mansson M, Nielsen A, Kjærulff L, Gotfredsen CH, Wietz M, Ingmer H, Gram L, Larsen TO. Inhibition of Virulence Gene Expression in Staphylococcus aureus by Novel Depsipeptides from a Marine Photobacterium. Marine Drugs. 2011; 9(12):2537-2552.
Mansson, Maria; Nielsen, Anita; Kjærulff, Louise; Gotfredsen, Charlotte H.; Wietz, Matthias; Ingmer, Hanne; Gram, Lone; Larsen, Thomas O. 2011. "Inhibition of Virulence Gene Expression in Staphylococcus aureus by Novel Depsipeptides from a Marine Photobacterium." Mar. Drugs 9, no. 12: 2537-2552.