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

Abstract

<title>Abstract</title> Background Study of the <italic>Pseudomonas aeruginosa</italic> 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 <italic>P. aeruginosa</italic> 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 <italic>P. aeruginosa</italic>. Repurposing of the already FDA-approved drugs is one of the promising strategies in combating <italic>Pseudomonas</italic> resistance or virulence. Results In this study we tested the anti-virulence effect of sub-minimum inhibitory concentration (MIC) of atorvastatin and rosuvastatin against <italic>P. aeruginosa.</italic> 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, <italic>in-vivo</italic> capability of statins to protect mice against <italic>P. aeruginosa</italic> was assessed, both drugs protected mice from <italic>P. aeruginosa</italic> 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 <italic>P. aeruginosa</italic>, locating it as a plausible potential therapeutic agent for the treatment of its infections.