In vitro antibacterial effects of statins against bacterial pathogens causing skin infections
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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.
KeywordsDrug repurposing Mechanism of action Paradoxical growth effect Skin infections Statins Topical antibiotics
The authors would like to acknowledge the kind contributions of the Australian Government Research Training Program Scholarship, the Curtin Health Innovation Research Institute (CHIRI) Biosciences Research Precinct Core Facility, and the School of Pharmacy and Biomedical Sciences (Curtin University) in supporting this research.
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Conflict of interest
The authors declare that they have no conflict of interest.
- 1.Tognetti L, Martinelli C, Berti S, Hercogova J, Lotti T, Leoncini F, Moretti S (2012) Bacterial skin and soft tissue infections: review of the epidemiology, microbiology, aetiopathogenesis and treatment: a collaboration between dermatologists and infectivologists. J Eur Acad Dermatol Venereol 26(8):931–941CrossRefPubMedGoogle Scholar
- 6.Collins R, Reith C, Emberson J, Armitage J, Baigent C, Blackwell L, Blumenthal R, Danesh J, Smith GD, DeMets D, Evans S, Law M, MacMahon S, Martin S, Neal B, Poulter N, Preiss D, Ridker P, Roberts I, Rodgers A, Sandercock P, Schulz K, Sever P, Simes J, Smeeth L, Wald N, Yusuf S, Peto R (2016) Interpretation of the evidence for the efficacy and safety of statin therapy. Lancet 388(10059):2532–2561CrossRefPubMedGoogle Scholar
- 13.Clinical and Laboratory Standards Institute (2012) Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard-ninth edition. CLSI document M07-A9. Wayne, Pennsylvania, USA: Clinical and Laboratory Standards Institute.Google Scholar
- 28.Duimel-Peeters I, Houwing R, Teunissen C, Berger M, Snoeckx L, Halfens R (2003) A systematic review of the efficacy of topical skin application of dimethyl sulfoxide on wound healing and as an anti-inflammatory. Wounds 15:316–370Google Scholar
- 32.Holm SE, Tornqvist IO, Cars O (1991) Paradoxical effects of antibiotics. Scand J Infect Dis 22(Suppl.74):113–117Google Scholar
- 37.Chen KX, Njoroge FG (2011) NS3 protease covalent inhibitors. In: Tan SL, He Y (eds) Hepatitis C: antiviral drug discovery and development. Caister Academic Press, United Kingdom, pp 169–192Google Scholar