In vitro antibacterial effects of statins against bacterial pathogens causing skin infections

Abstract

With financial considerations impeding research and development of new antibiotics, drug repurposing (finding new indications for old drugs) emerges as a feasible alternative. Statins are extensively prescribed around the world to lower cholesterol, but they also possess inherent antimicrobial properties. This study identifies statins with the greatest potential to be repurposed as topical antibiotics and postulates a mechanism of action for statins' antibacterial activity. Using broth microdilution, the direct antibacterial effects of all seven parent statins currently registered for human use and three selected statin metabolites were tested against bacterial skin pathogens Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Serratia marcescens. Simvastatin and pitavastatin lactone exerted the greatest antibacterial effects (minimum inhibitory concentrations of 64 and 128 μg/mL, respectively) against S. aureus. None of the statins tested were effective against E. coli, P. aeruginosa, or S. marcescens, but simvastatin hydroxy acid acid might be active against S. aureus, E. coli, and S. marcescens at drug concentrations > 256 μg/mL. It was found that S. aureus may exhibit a paradoxical growth effect when exposed to simvastatin; thus, treatment failure at high drug concentrations is theoretically probable. Through structure-activity relationship analysis, we postulate that statins' antibacterial action may involve disrupting the teichoic acid structures or decreasing the number of alanine residues present on Gram-positive bacterial cell surfaces, which could reduce biofilm formation, diminish bacterial adhesion to environmental surfaces, or impede S. aureus cell division.

Strategies to Combat Persistent Infectious Diseases

“…Taken together, these studies suggest a potential bactericidal activity of simvastatin alone or in combination with topical antimicrobials currently used to treat MRSA skin infections. One year ago, the antibacterial effects of statins in vitro were verified against skin pathogens as S. aureus, E. coli, P. aeruginosa and Serratia marcescens [85].…”

Strategies to Combat Multidrug-Resistant and Persistent Infectious Diseases

“…The in vitro antibacterial effects of statins against skin pathogens such as S. aureus, E. coli, P. aeruginosa, and Serratia marcescens were verified in a recent study [85].…”

<p>Effect of Statins on the Risk of Poststroke Pneumonia: National Population-Based Cohort Study</p>

“… 44 Furthermore, statins may exhibit antibacterial activity that interrupts bacterial cell functions via binding and disruption of cell-wall structures such as teichoic acids, lipoteichoic acids, LPSs, and surface proteins. 45 Modulation of gene expression in immune cells and cell-adhesion molecules by statins may reduce replication of viruses, including influenza. 46 By promotion of the host-defense mechanism and inhibition of pathological inflammation, statins may play a beneficial protective role against infectious diseases.…”