Anti-quorum, anti biofilm activity of FDA approved drugs against P. aeruginosa: in silico and in vitro studies
摘要
P. aeruginosa is an opportunistic pathogen that causes various nosocomial infections. The ability of P. aeruginosa to form biofilms is one of the main factors contributing to its pathogenicity. Due to biofilm formation, bacteria get embedded in it and is able to withstand extreme environmental conditions like chemicals, UV, temperature, pH, salinity, and antibiotics. Biofilm formation is an important virulence factor associated with quorum sensing (QS), which is a cell-to-cell communication system that is influenced by cell density. P. aeruginosa is a notorious pathogen that is known to cause severe complications in patients suffering from cystic fibrosis and immuno-compromised individuals in hospital setting as a result of biofilm formation. We might limit P. aeruginosa infection pathogenesis and biofilm formation if we can disrupt the signalling molecules involved in QS. In this study, we suggested that already-approved medications by the FDA could be employed as anti-quorum and anti-biofilm agents and potentially be helpful in curing P. aeruginosa associated infections. The anti-quorum and anti-biofilm properties of FDA-approved medications have been investigated here. We have also performed RT-PCR analysis and molecular docking experiments to assess the mechanism of action of these drugs. We have found that all four drugs have anti QS activity. Out of these four drugs Flurbiprofen was found to be more effective. RT data confirms that these drugs have significantly downregulated all four QS gene and therefore are able to inhibit the P. aeruginosa virulence factors. This study significantly opens up the new horizons for the development of novel therapeutics against P. aeruginosa and infections associated with it.