Modulating Pseudomonas aeruginosa virulence by the anti-cholesterol drugs Atorvastatin and Rosuvastatin

Background Study of the Pseudomonas aeruginosa resistance has become an urgent topic since antibiotic resistance has escalated exceedingly. Even with the intense interest, development of new antibiotics and other therapeutic strategies for P. aeruginosa infections is at a painstakingly slow pace due to the complexity of drug resistance, as well as the lack of a deep understanding of the pathogenic mechanisms for P. aeruginosa . Repurposing of the already FDA-approved drugs is one of the promising strategies in combating Pseudomonas resistance or virulence. Results In this study we tested the anti-virulence effect of sub-minimum inhibitory concentration (MIC) of atorvastatin and rosuvastatin against P. aeruginosa. The assessed virulence factors include: biofilm formation and production of pyocyanin, protease, hemolysin and rhamnolipids. Significantly, atorvastatin and rosuvastatin decreased the production of bacterial biofilm and reduced other virulence factors. Moreover, the anti-quorum sensing (QS) activity of atorvastatin and rosuvastatin was assessed using qRT-PCR. the expression of QS genes was reduced using atorvastatin and rosuvastatin. Furthermore, in-vivo capability of statins to protect mice against P. aeruginosa was assessed, both drugs protected mice from P. aeruginosa and enhanced their survival. In addition, molecular docking was used to evaluate binding between statin and QS-receptors, rosuvastatin showed better interaction with QS-receptors than atorvastatin, as rosuvastatin has higher binding scores with LasR, RhlR, and LasB, while atorvastatin showed higher binding with the PqsR. Conclusion statins attenuated the pathogenicity of P. aeruginosa , locating it as a plausible potential therapeutic agent for the treatment of its infections.