Analysis of the Impact of Rosuvastatin on Bacterial Mevalonate Production Using a UPLC-Mass Spectrometry Approach

Nolan, J. A. and Kinsella, M. and Hill, C. and Joyce, S. A. and Gahan, C. G.M. (2016) Analysis of the Impact of Rosuvastatin on Bacterial Mevalonate Production Using a UPLC-Mass Spectrometry Approach. Current Microbiology, 73 (1). pp. 1-8. ISSN 0343-8651

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Statins are widely prescribed cholesterol-lowering medications and act through inhibition of the human enzyme 3-methylglutaryl coenzyme A reductase (HMG-R) which produces mevalonate (MVAL), a key substrate for cholesterol biosynthesis. Some important microbial species also express an isoform of HMG-R; 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 dose-dependent inhibition of growth in the HMG-R+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 ultra-performance liquid chromatography mass spectrometry protocol. This work therefore outlines a refined protocol for the analysis of MVAL in microbial cultures and provides evidence for statin-mediated inhibition of bacterial HMG-R. Furthermore, we show that MVAL is readily transported and secreted from bacterial cells into the growth media.

Item Type: Article
Additional Information: Funding Information: J.A.N. 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 co-funded 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. Publisher Copyright: © 2016, Springer Science+Business Media New York.
Uncontrolled Keywords: /dk/atira/pure/subjectarea/asjc/2400/2404
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Depositing User: Admin SSL
Date Deposited: 19 Oct 2022 23:01
Last Modified: 07 Jun 2023 18:41

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