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


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2016-03-10

AUTHORS

J. A. Nolan, M. Kinsella, C. Hill, S. A. Joyce, C. G. M. Gahan

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. More... »

PAGES

1-8

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00284-016-1014-z

DOI

http://dx.doi.org/10.1007/s00284-016-1014-z

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https://app.dimensions.ai/details/publication/pub.1046418218

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26960292


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217 grid-institutes:grid.24349.38 schema:alternateName Department of Science, School of Science & Computing, Waterford Institute of Technology, Waterford, Ireland
218 schema:name Department of Science, School of Science & Computing, Waterford Institute of Technology, Waterford, Ireland
219 School of Food and Nutritional Sciences, University College Cork, Cork, Ireland
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221 grid-institutes:grid.7872.a schema:alternateName School of Biochemistry & Cell Biology, University College Cork, Cork, Ireland
222 School of Microbiology, University College Cork, Cork, Ireland
223 School of Pharmacy, University College Cork, Cork, Ireland
224 schema:name APC Microbiome Institute, University College Cork, Cork, Ireland
225 School of Biochemistry & Cell Biology, University College Cork, Cork, Ireland
226 School of Microbiology, University College Cork, Cork, Ireland
227 School of Pharmacy, University College Cork, Cork, Ireland
228 rdf:type schema:Organization
 




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