Abstract

Polybacterial infections of the lung are the foremost cause of morbidity and mortality in cystic fibrosis (CF) patients. There is an increasing appreciation for the important role that interspecies interactions play during infection in influencing both pathogenesis and response to therapy. The CF airway is often co-infected with Pseudomonas aeruginosa and other pathogens including Burkholderia cenocepacia and Stenotrophomonas maltophilia. These latter pathogens produce signal molecules of the diffusible signal family, which are cis-2-unsaturated fatty acids. Recently, we have shown by various in vitro and in vivo studies that DSF leads to altered biofilm formation and increased resistance to antibiotics by P. aeruginosa. The response of P. aeruginosa to this class of signal molecule requires the sensor kinase PA1396. Furthermore, we have also established that these signal molecules are present in the airways of CF patients and that they influence P. aeruginosa during infection. Given the role that DSF signalling appears to play in virulence and biofilm development in P. aeruginosa, we have begun to investigate the use of various DSF analogues as a route towards interference with this signalling system in order to enhance frontline antibiotics to eliminate P. aeruginosa. The combination of various antibiotics with DSF analogues reduced established biofilm biomass and viable bacteria. Neither antibiotics nor analogues of DSF alone had such a marked effect. Taken together, our data provides substantial evidence that interspecies DSF-mediated bacterial interactions occur in the CF airway and may influence the efficacy of antibiotic treatment. Additionally, it appears that interference with DSF signalling may provide a route for therapeutic intervention for many infections characterised by antibiotic-resistant P. aeruginosa.

Biography

Dr Robert Ryan is recently appointed Wellcome Trust Senior Investigator in the Divison of Molecular Microbiology. In 2004, he gained a PhD in Molecular Microbiology from Trinity College Dublin. Subsequent years under the auspicious of EMBO, HFSP, SFI and Royal Irish Academy fellowships he worked in the laboratories in the Karolinska Institute, Universidade de São Paulo, University of Copenhagen and Dartmouth Medical School. Most recently he was awarded the Lister Institute Research Prize Fellowship award, which seeks to help support and nurture future leaders in biosciences and genetics. His current work centers around understanding the role that interspecies signalling plays in influencing both bacterial virulence and response to therapy in various polymicrobial infections.