Identifying biofilm regulators as novel targets for antimicrobial drug design

Abstract

Antibiotic treatment regularly fails to cure patients suffering from infections caused by adaptively resistant microbial communities, referred to as biofilms. Even though at least two thirds of all clinical infections are associated with biofilms, there are no biofilm-specific therapies on the market or in clinical trials. Pseudomonas aeruginosa is a remarkably antibiotic resistant, nosocomial pathogen and biofilm-former that causes morbidity and mortality especially in cystic fibrosis and immunocompromised patients. This project aims to identify regulatory genes associated with drug resistance in P. aeruginosa biofilms to provide novel biofilm-specific targets for the design of potent drugs. A genome-wide screen of P. aeruginosa burn wound isolate UCBPP-PA14 identified 362 genes involved in biofilm formation, including dozens of regulatory and hypothetical genes. I will discuss regulatory as well as metabolic genes corresponding to the known resistome of antimicrobials.