Engineering of N-Acyl Homoserine Lactone (AHL) genes in the quorum-sensing of Pseudomonas

Hundreds of millions of patients every year acquire an infection from their healthcare setting, according to the World Health Organisation. Treating these nosocomial infections is complicated by antibiotic resistance; there has been a rapid increase of multidrug resistance (MDR) bacteria, including strains of the gram-negative genera, Pseudomonas and Escherichia. Opportunistic Pseudomonas are responsible for 10% of all global hospital acquired infections which cause disease in immuno-deficient individuals. In cystic fibrosis, Pseudomonas aeruginosa is estimated to colonise the lungs of 50-90% of patients. A major contributor to bacterial antibiotic resistance is the aggregation of bacteria to form biofilms. Bacteria within biofilms communicate with each other through the release of chemicals, such as N-Acyl homoserine lactones (AHL), these quorum-sensing molecules are essential to biofilm formation. This project will aim to develop strategies to inhibit biofilm formation by targeting the specific genes responsible for AHL regulation; ppuR, ppuA, ppuI and RsaL in Pseudomonas putida. This project has a vast range of potential therapeutic applications such as development of biocontainment devices against MDR bacteria. This project will provide a fundamental contribution to understanding and combating antibiotic resistance with applications for treating nosocomical infections