Exploration of efflux footprint of multidrug resistant Candida auris using a chemical biology approach.

K Miraz Rahman (primary)
Institute of Pharmaceutical Science
King's College London
Dr Barry Panaretou (secondary)
Institute of Pharmaceutical Science
King's College London

Abstract

One of the key elements in the resistance of Candida species and other fungi to anti-fungals, relates to efflux, a process which expels the drug from the fungus minimising the intracellular concentration and reducing efficacy. This is a common component of both intrinsic resistance to an antifungal and a necessary first step in adaptation to resistance to a new therapy. By improving our understanding of efflux in C.auris, a yeast with a battery of highly expressed drug pumps, we hope to be able to better understand its role in clinical resistance and design improved strategies for overcoming efflux-mediated resistance in new chemical series.


References

1. Chen Y, Hind C, Sutton M and Rahman K. M. (2020), New Efflux Resistant Antifungal Compounds, UK Patent Application No GB2001564

2. Chowdhary, A., Sharma, C. & Meis, J. F. (2017), Candida auris: a rapidly emerging cause of hospital-acquired multidrug-resistant fungal infections globally. PLoS pathogens 13, e1006290

3. Jamshidi, S., Sutton, J. M., and Rahman, K. M. (2018) Mapping the Dynamic Functions and Structural Features of AcrB Efflux Pump Transporter Using Accelerated Molecular Dynamics Simulations, Scientific Reports 8, 10470.

4. Zhai C, Li Y, Mascarenhas C, Lin Q, Li K, Vyrides I, Grant CM, Panaretou B. (2014)The function of ORAOV1/LTO1, a gene that is overexpressed frequently in cancer: essential roles in the function and biogenesis of the ribosome. Oncogene 33(4):484-94

5. Prescott T.A., Panaretou B, Veitch N.C., Simmonds M.S. (2014) A yeast chemical genetics approach identifies the compound 3,4,5-trimethoxybenzyl isothiocyanate as a calcineurin inhibitor. FEBS Letters 588(3):455-8


BBSRC Area
Plants, microbes, food and sustainability
Area of Biology
Chemical BiologyMicrobiology
Techniques & Approaches
BiochemistryBioinformaticsBiophysicsChemistryMolecular BiologySimulation / Modelling