Title:Anti-virulence therapy against Staphylococcus aureus: Possibilities and challenges
Presenter: Prof. Hanne Ingmer
University: Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen
Time: 10:00-11:30, May 8, 2013
Venue: Room A203, Institute of Microbiology, Chinese Academy of Sciences
Abstract: Methicillin-resistant Staphylococcus aureus (MRSA) continues to be a serious human pathogen. Particularly the spread of community associated (CA)-MRSA strains such as USA300 is concerning, as these strains can cause severe infections in otherwise healthy adults. As antibiotic resistance is a widespread problem for S. aureus alternative therapeutic approaches are being sought. Among these is anti-virulence therapy where virulence rather than growth is inhibited. To identify putative anti-virulence compounds we have search fungi and the marine environments for compounds that interfere with the agr quorum sensing system in control of virulence gene expression in S. aureus. The agr locus comprises agrC encoding the sensor histidine kinase, agrA encoding the response regulator as well as RNAIII, the effector molecule. Quorum sensing is mediated via expression of an autoinducing peptide that is sensed in a concentration dependent manner by AgrC. Surprisingly both fungi and marine microorganisms yielded multiple candidate compounds that reduced agr activity and we have pursued characterization of a cyclodepsipeptide termed Solonamide B isolated from the marine bacterium, Photobacterium halotolerans and norlichexanthone isolated from the fungus Penicillium algidum. While the norlichexanthoe seems to interfere with signaling through the Sae two component system, the solonamide B competitively interferes with AgrC and represses expression of both RNAIII and AgrA the agr response regulator. In consequence expression of both -henolysin and the phenol soluble modulins is strongly reduced. Our data suggest that compounds are readily isolated from various environmental habitats that interfere with agr and we speculate that the agr system may wider communication abilities than previously anticipated.