title: Analysis of the Impact of Rosuvastatin on Bacterial Mevalonate Production Using a UPLC-Mass Spectrometry Approach.
abstract: 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.
authors.affiliation: APC Microbiome Institute, University College Cork, Cork, Ireland.|School of Microbiology, University College Cork, Cork, Ireland.
authors.forename: J A
authors.initials: JA
authors.lastname: Nolan
authors.affiliation: School of Food and Nutritional Sciences, University College Cork, Cork, Ireland.|Department of Science, School of Science & Computing, Waterford Institute of Technology, Waterford, Ireland.
authors.forename: M
authors.initials: M
authors.lastname: Kinsella
authors.affiliation: APC Microbiome Institute, University College Cork, Cork, Ireland.|School of Microbiology, University College Cork, Cork, Ireland.
authors.forename: C
authors.initials: C
authors.lastname: Hill
authors.affiliation: APC Microbiome Institute, University College Cork, Cork, Ireland. s.joyce@ucc.ie.|School of Biochemistry & Cell Biology, University College Cork, Cork, Ireland. s.joyce@ucc.ie.
authors.forename: S A
authors.initials: SA
authors.lastname: Joyce
authors.affiliation: APC Microbiome Institute, University College Cork, Cork, Ireland. c.gahan@ucc.ie.|School of Microbiology, University College Cork, Cork, Ireland. c.gahan@ucc.ie.|School of Pharmacy, University College Cork, Cork, Ireland. c.gahan@ucc.ie.
authors.forename: C G M
authors.initials: CG
authors.lastname: Gahan
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D016984:Enterococcus faecium / Q000737:chemistry / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D008089:Listeria monocytogenes / Q000737:chemistry / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D013058:Mass Spectrometry / Q000379:methods*; D008798:Mevalonic Acid / Q000378:metabolism*; D000068718:Rosuvastatin Calcium / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000737:chemistry / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism
chemical_list: D000068718:Rosuvastatin Calcium; D008798:Mevalonic Acid