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. 2011 Dec;9(12):2537-2552.
doi: 10.3390/md9122537. Epub 2011 Dec 7.

Inhibition of virulence gene expression in Staphylococcus aureus by novel depsipeptides from a marine photobacterium

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Inhibition of virulence gene expression in Staphylococcus aureus by novel depsipeptides from a marine photobacterium

Maria Mansson et al. Mar Drugs. 2011 Dec.

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; agr; antivirulence; quorum sensing inhibition.

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Figures

Figure 1
Figure 1
Effect of solonamides (A and B) on hla, rnaIII and spa expression. Solonamides (5 mg mL−1) were added to wells in TSA plates containing the 8325-4 derived lacZ reporter strains PC322 (hla::lacZ), SH101F7 (rnaIII::lacZ), or PC203 (spa::lacZ). Incubation time was 15 h for plate I and II, and 35 h for plate III (plate numbering indicated with white letters). Solonamide B tested in two wells.
Figure 2
Figure 2
Structures of solonamides A and B produced by Photobacterium sp. strain S2753 and structure of natural group I AIP [21].
Figure 3
Figure 3
Distribution of the Δδ values (ppm) calculated for the (a) 3-hydroxyhexanoic acid (Hha) and (b) 3-hydroxyoctanoic acid (Hoa) in the (R)- and (S)-Mosher’s esters.
Figure 4
Figure 4
Effect of solonamide A and B on virulence gene expression in S. aureus strain 8325-4 [18] and USA300 [55] examined by Northern blot analysis. Solonamides were added to exponentially growing cultures at OD600 = 0.4, and RNA was purified at OD600 = 0.7 and 1.7. The RNA was reacted with probes recognizing hla, rnaIII, and spa, respectively. Solonamide B tested in duplicates. DMSO was used as negative control.

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