Structurally-guided identification of novel pharmacophores targeting Pseudomonas aeruginosa quorum sensing and biofilm formation

Principal Investigator: Dr Lidija Senerovic

Antibiotic resistance for both Gram-positive and Gram-negative pathogens is spreading worldwide at an increasing rate, presenting a challenging global health problem. The aim of this project is to discover and develop leads for new antimicrobial agents targeting bacterial biofilms, which are common sources of lower sensitivity or even resistance to antibiotics. Both historically and at the present time microbial natural products have been the major source of new drugs. Most clinical antibiotics are natural products or inspired by natural products. They usually came from screens of Actinomyces, soil-dwelling bacteria which are well-known for their production of valuable metabolites. During this project we will screen our untapped Streptomycetes culture collection accumulated for 20 years from variety of sources and ecological niches and search for the specific small molecules interfering with bacterial virulence rather than viability. Targeting bacterial virulence reduces selective pressure, which can decrease possibility to develop drug resistance and keeps the host endogenous microflora intact. Our screening will be based on bio-assays against P. aeruginosa quorum sensing-regulated biofilm formation.