Statin resistance in Candida glabrata
Reduced efficacy of statins has been observed in people but the mechanism of this resistance is unclear and no statin-resistance mutations in the catalytic domain of HMGCR have been reported. The present study focused on looking for statin-resistance mutations and examining the mechanism of statin resistance using Candida glabrata as a model organism.
C. glabrata was cultured in media containing lovastatin, simvastatin or atorvastatin to obtain lovastatin-, simvastatin- and atorvastatin-resistant mutants. A single mutant from each was purified for further analysis. In each mutant, gene sequencing showed there were no changes in the catalytic domain of HMGCR. HMGCR was overexpressed in two resistant isolates suggesting that increased production of HMGCR can lead to resistance. In a third mutant, HMGCR activity was unaltered, suggesting a non-HMGCR related mechanism, such as increased drug efflux, could be operating.
Candida glabrata is a useful model organism for examining resistance to statins. Further studies are warranted to examine the precise molecular mechanisms of statin resistance.
KeywordsCandida glabrata Cholesterol HMG-CoA reductase Statin resistance Yeast
We thank HEC and Quaid-I-Azam University Pakistan and RMIT University for their generous support and providing opportunity for the collaboration.
This work was supported by the Higher Education commission of Pakistan [1-8/HEC/HRD/2015/3989 to M.S] under International support initiative programme [IRSIP GR 29 BMS 52].
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- de Keyser CE, Eijgelsheim M, Hofman A, Sijbrands EJG, Maitland-van der Zee AH, van Duijn CM, Uitterlinden AG, Witteman JCM, Ch Stricker BH (2011) Single nucleotide polymorphisms in genes that are associated with a modified response to statin therapy: the Rotterdam Study. Pharmacogenomics J 11:72–80CrossRefPubMedGoogle Scholar
- McKimm-Breschkin JL, Sahasrabudhe A, Blick TJ, McDonald M, Colman PM, Hart GJ, Bethell RC, Varghese JN (1998) Mutations in a conserved residue in the influenza virus neuraminidase active site decreases sensitivity to Neu5Ac2en-derived inhibitors. J Virol 72:2456–2462PubMedPubMedCentralGoogle Scholar
- Simon JA, Lin F, Hulley SB, BlanchePJ Waters D, Shiboski S, Rotter JI, Nickerson DA, Yang H, Saad M, Krauss RM (2006) Phenotypic predictors of response to simvastatin therapy among African-Americans and Caucasians: the cholesterol and pharmacogenetics (CAP) study. Am J Cardiol 97:843–850CrossRefPubMedGoogle Scholar