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

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

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Main Authors: Ko, H., Lareu, R., Dix, B., Hughes, Jeff
Format: Journal Article
Published: Springer 2018
Online Access:http://hdl.handle.net/20.500.11937/66945
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author Ko, H.
Lareu, R.
Dix, B.
Hughes, Jeff
author_facet Ko, H.
Lareu, R.
Dix, B.
Hughes, Jeff
author_sort Ko, H.
building Curtin Institutional Repository
collection Online Access
description © 2018 Springer-Verlag GmbH Germany, part of Springer Nature 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.
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spelling curtin-20.500.11937-669452018-05-18T08:07:11Z In vitro antibacterial effects of statins against bacterial pathogens causing skin infections Ko, H. Lareu, R. Dix, B. Hughes, Jeff © 2018 Springer-Verlag GmbH Germany, part of Springer Nature 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. 2018 Journal Article http://hdl.handle.net/20.500.11937/66945 10.1007/s10096-018-3227-5 Springer restricted
spellingShingle Ko, H.
Lareu, R.
Dix, B.
Hughes, Jeff
In vitro antibacterial effects of statins against bacterial pathogens causing skin infections
title In vitro antibacterial effects of statins against bacterial pathogens causing skin infections
title_full In vitro antibacterial effects of statins against bacterial pathogens causing skin infections
title_fullStr In vitro antibacterial effects of statins against bacterial pathogens causing skin infections
title_full_unstemmed In vitro antibacterial effects of statins against bacterial pathogens causing skin infections
title_short In vitro antibacterial effects of statins against bacterial pathogens causing skin infections
title_sort in vitro antibacterial effects of statins against bacterial pathogens causing skin infections
url http://hdl.handle.net/20.500.11937/66945