PQS quorum sensing communication system
Development of molecules that interfere with the PQS quorum sensing communication system in Pseudomonas aeruginosa
The department is working on the development of compounds interfering with the PQS quorum sensing cell-to-cell-communication system in Pseudomonas aeruginosa. Lung infections resulting from this opportunistic ESKAPE pathogen are regarded as one of the major causes of morbidity and mortality in patients with cystic fibrosis. Resistance to generally applied antibiotics is often associated with biofilm formation.
Both the formation of biofilms as well as the production of virulence factors is regulated by a complex quorum sensing communication network. Within this network, bacteria coordinate population-wide behaviours in a cell-density-dependent manner. In addition to the quorum sensing networks LasR and RhlR, which are present in numerous bacteria, P. aeruginosa uses a third communication system. This system is regulated by PQS (Pseudomonas Quinoline Signal, 2-heptyl-3-hydroxy-4-quinolone) as an intercellular signalling molecule.
The overall aim of the project is to discover and advance compounds for the treatment of P. aeruginosa infections. These anti-infective agents interfere with PQS quorum sensing communication in order to prevent biofilm formation and to reduce the production of multiple quorum sensing-regulated virulence factors without affecting bacterial viability. This novel anti-infective strategy circumvents usual resistance mechanisms and could lead to low rates of resistance development, while the pathogen-specific mode-of-action preserves the commensal (beneficial) microbiota.
- Drug Design and Optimization- Prof. Dr. Anna K. H. Hirsch
Martin Empting und Rolf Müller