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.
Highlights
Microorganisms are an attractive source of new natural products with antimicrobial properties [1,2], and the marine environment constitutes a prolific resource of bioactive microorganisms [3,4,5]
In an initial search for antimicrobial compounds we isolated strain S2753 related to Photobacterium halotolerans [29]
Virulence of S. aureus involves a complex set of proteins, with the agr quorum sensing (QS) system controlling expression of several of the virulence genes
Summary
Microorganisms are an attractive source of new natural products with antimicrobial properties [1,2], and the marine environment constitutes a prolific resource of bioactive microorganisms [3,4,5]. Many marine microenvironments stimulate the production of specific metabolites as a response to environmental factors [6]. The search for new avenues in microbial control has been extended from traditional bacteriostatic or bacteriolytic compounds to compounds that target, for example, quorum sensing (QS) pathways [9,10,11]. Quorum sensing inhibitors (QSI) do not necessarily kill or inhibit the growth of a pathogen but rather modulate microbial phenotypes, for example by attenuating virulence [12,13]. In vivo studies with QS inhibitory compounds demonstrated how these can be used to slow the spread of infection [14] or enhance the clearance of pathogens from infected tissue [10]
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