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Title of Journal: Curr Microbiol

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Abbravation: Current Microbiology

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Springer US

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DOI

10.1002/andp.18531650607

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1432-0991

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Analysis of the Impact of Rosuvastatin on Bacteria

Authors: J A Nolan M Kinsella C Hill S A Joyce C G M Gahan
Publish Date: 2016/03/10
Volume: 73, Issue: 1, Pages: 1-8
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Abstract

Statins are widely prescribed cholesterollowering medications and act through inhibition of the human enzyme 3methylglutaryl coenzyme A reductase HMGR which produces mevalonate MVAL a key substrate for cholesterol biosynthesis Some important microbial species also express an isoform of HMGR however the nature of the interaction between statins and bacteria is currently unclear and studies would benefit from protocols to quantify MVAL in complex microbial environments The objective of this study was to develop a protocol for the analytical quantification of MVAL in bacterial systems and to utilise this approach to analyse the effects of Rosuvastatin RSV on bacterial MVAL formation To determine the effective concentration range of RSV we examined the dosedependent inhibition of growth in the HMGR+ bacterial pathogens Listeria monocytogenes Staphylococcus aureus and Enterococcus faecium at various concentrations of pure RSV Growth inhibition generally correlated with a reduction in bacterial MVAL levels particularly in culture supernatants at high RSV concentrations as determined using our ultraperformance liquid chromatography mass spectrometry protocol This work therefore outlines a refined protocol for the analysis of MVAL in microbial cultures and provides evidence for statinmediated inhibition of bacterial HMGR Furthermore we show that MVAL is readily transported and secreted from bacterial cells into the growth mediaJAN was funded by an EMBARK postgraduate research scholarship from the Irish Research Council for Science Engineering and Technology IRCSET The mass spectrometry instrument and analysis was funded under the Higher Education Authority Programme for Research in Third Level Institutions PRTLI cycle 4 and cofunded under the European Regional Development Fund This publication has emanated from research conducted with the financial support of Science Foundation Ireland SFI under Grant Number SFI/12/RC/2273

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