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

  • Humphrey H. T. Ko
  • Ricky R. Lareu
  • Brett R. Dix
  • Jeffery D. Hughes
Original Article

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.

Keywords

Drug repurposing Mechanism of action Paradoxical growth effect Skin infections Statins Topical antibiotics 

Notes

Acknowledgements

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.

Compliance with ethical standards

Ethical approval

Not applicable.

Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent

Not applicable.

Supplementary material

10096_2018_3227_MOESM1_ESM.docx (974 kb)
ESM 1 (DOCX 974 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Humphrey H. T. Ko
    • 1
    • 2
  • Ricky R. Lareu
    • 1
    • 2
  • Brett R. Dix
    • 1
  • Jeffery D. Hughes
    • 1
  1. 1.School of Pharmacy and Biomedical Sciences, Faculty of Health SciencesCurtin UniversityPerthAustralia
  2. 2.Curtin Health Innovation Research Institute (CHIRI) Biosciences Research PrecinctCurtin UniversityPerthAustralia

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