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Biotechnology Letters

, Volume 40, Issue 9–10, pp 1389–1394 | Cite as

Statin resistance in Candida glabrata

  • Mishal Subhan
  • Rani Faryal
  • Ian Macreadie
Original Research Paper

Abstract

Objectives

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.

Results

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.

Conclusions

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.

Keywords

Candida glabrata Cholesterol HMG-CoA reductase Statin resistance Yeast 

Notes

Acknowledgements

We thank HEC and Quaid-I-Azam University Pakistan and RMIT University for their generous support and providing opportunity for the collaboration.

Funding

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.

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Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  1. 1.School of ScienceRMIT UniversityBundooraAustralia
  2. 2.Department of Microbiology, Faculty of Biological SciencesQuaid-i-Azam UniversityIslamabadPakistan

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