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.

Structural and functional comparison of Saccharomonospora azurea strains in terms of primycin producing ability

“…Genes corresponding to Lrp/AsnC family transcriptional regulators were found substantially up-regulated in high-primycin producer strains. Present findings were in agreement with previously reported facts that, genes encoding the Lrp/AsnC family transcriptional regulators (SCO2140 and SCO3361) act as positive regulators of antibiotic production in S. coelicolor (Liu et al 2017 ; Yu et al 2016 ).…”

Biofilm Formation of Staphylococcus aureus under Food Heat Processing Conditions: First Report on CML Production within Biofilm

“…To date, evidences of ica -independent pathways for biofilm forming have been confirmed 63 , and this phenomenon was observed frequently under various conditions 64,65 . In ica -independent pattern, extracellular matrix such as Spa and Bap act as compensatory substances for PIA in S. aureus biofilm 25 .…”

“…For CML level in S. aureus biofilm, according to our previous study, active metabolism was conducted inside the biofilm for colony proliferation, eDNA and EPS synthesis, as well as their secretion in maturation stage 65 , which may lead a dramatic increasement of CML level. However, there’s no evidences indicating that the accumulation of CML was accompanied by the metabolic activity of S. aureus biofilm.…”

Effects of Enterobacter cloacae HG-1 on the Nitrogen-Fixing Community Structure of Wheat Rhizosphere Soil and on Salt Tolerance

“…The IAA concentration in crops was significantly reduced after salt stress; for instance, the IAA concentration was decreased by approximately 75% in tomato plants ( Dunlap and Binzel, 1996 ). Furthermore, when the isolates of salt-tolerant IAA strains B. endophyticus , B. tequilensis , and Planococcus were re-inoculated into salt-tolerant grass, the germination rate of grass increased by 7%–11%, the shoot length increased by 13%–22%, the root length increased by 44%–57%, and the FW increased by 21%–54% compared with uninoculated plants ( Zhao et al., 2016 ). Gibberellin (GA) is involved in several stages of plant growth and development, including seed germination, leaf growth, photolithogenesis, shoot elongation, flower organ development, and fruit maturation.…”