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Review
. 2016 Aug 22;60(9):5111-21.
doi: 10.1128/AAC.00192-16. Print 2016 Sep.

Is There Potential for Repurposing Statins as Novel Antimicrobials?

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Free PMC article
Review

Is There Potential for Repurposing Statins as Novel Antimicrobials?

Emma Hennessy et al. Antimicrob Agents Chemother. .
Free PMC article

Abstract

Statins are members of a class of pharmaceutical widely used to reduce high levels of serum cholesterol. In addition, statins have so-called "pleiotropic effects," which include inflammation reduction, immunomodulation, and antimicrobial effects. An increasing number of studies are emerging which detail the attenuation of bacterial growth and in vitro and in vivo virulence by statin treatment. In this review, we describe the current information available concerning the effects of statins on bacterial infections and provide insight regarding the potential use of these compounds as antimicrobial therapeutic agents.

Figures

FIG 1
FIG 1
Chemical structures of statins. (A) Type 1 statins are characterized by a conserved lactone ring (blue), a decahydronaphthalene (Decalin) structure (black), and a butyryl side chain which is different in each statin (red). (B) Type 2 statins differ from type 1 statins due to the replacement of the butyryl side chain with a fluorophenyl group (green), and although the lactone ring structure is conserved in all statins, the decahydronaphthalene group of type 1 statins is replaced by a longer distinct side chain. Statins marked with an asterisk (*) are licensed for treatment of high cholesterol.
FIG 2
FIG 2
Statins modulate bacterial growth and virulence. (A) In vitro effects of statins on bacterial species. Statins reduce in vitro bacterial growth, motility, and attachment. (B) Key antivirulence mechanisms of statins. At physiological concentrations, statin treatment can reduce bacterial invasion and translocation in addition to inhibiting lipid raft production. The inhibition of Rho GTPase activity and cholesterol production by statins contributes to reduced bacterial virulence, decreased toxicity, and impaired intracellular survival. (C) At physiological concentrations, statin treatment can reduce bacterial load and dissemination and increase bacterial clearance in mouse models of infection.

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