Related Experiment Video
Updated: Jun 5, 2025
Small-Scale Plasma Membrane Preparation for the Analysis of Candida albicans Cdr1-mGFPHis
Published on: June 13, 2021
Identification of ABC transporter Cdr1 inhibitors of Candida glabrata
Mohd Waseem1, Shubhashis Das2, Debarati Mondal3
1School of Computational and Integrative Sciences, Jawaharlal Nehru University, New Delhi, 110067, India; Plant Transcription Regulation Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, 110067, India.
Abstract:
Candida glabrata is one of the most common causes of invasive candidiasis. Rising treatment failures from resistance to current antifungal drugs highlight the need for new antifungals. Overexpression of efflux pump transporter genes is significantly associated with the development of multidrug resistance. In this study, we have identified novel and potential inhibitors of ABC transporter Cdr1 of Candida glabrata (CgCdr1) by employing high throughput virtual screening of large chemical datasets from five different chemical libraries (ZINC, DrugBank, ChemDiv antifungal, ChemDiv Kinases, and ChEMBL bioassay). As a result many molecules were predicted to have higher binding affinity toward the CgCdr1, in which a naturally occurring compound, pentagalloyl glucose, was identified to significantly reduce the growth of Candida glabrata with an IC50 value of 16.97 ± 2.1 μM. Molecular dynamics studies showed stable binding of pentagalloyl glucose with CgCdr1 protein. In summary, our research identifies pentagalloyl glucose as a novel antifungal compound that has the potential to be used for inhibiting the growth of Candida glabrata.
Insights
A natural compound, pentagalloyl glucose, effectively inhibits Candida glabrata growth by targeting the CgCdr1 efflux pump. This discovery offers a promising new avenue for developing antifungal treatments against drug-resistant infections.
Area of Science:
- Mycology
- Biochemistry
- Pharmacology
Background:
- Invasive candidiasis, often caused by Candida glabrata, is a growing concern due to increasing antifungal resistance.
- Multidrug resistance in Candida glabrata is frequently linked to the overexpression of efflux pump transporter genes, such as ABC transporter Cdr1.
- The urgent need for novel antifungal agents necessitates the identification of new therapeutic targets and inhibitors.
Purpose of the Study:
- To identify novel inhibitors of the ABC transporter CgCdr1 in Candida glabrata.
- To screen large chemical libraries for compounds with high binding affinity to CgCdr1.
- To evaluate the antifungal potential of identified compounds against Candida glabrata.
Main Methods:
- High throughput virtual screening of five diverse chemical libraries (ZINC, DrugBank, ChemDiv antifungal, ChemDiv Kinases, ChEMBL bioassay).
- In silico prediction of binding affinity to the CgCdr1 transporter.
- In vitro assessment of growth inhibition using IC50 values.
- Molecular dynamics simulations to analyze compound-protein interactions.
Main Results:
- Several molecules showed predicted high binding affinity to CgCdr1.
- Pentagalloyl glucose, a natural compound, demonstrated significant inhibition of Candida glabrata growth with an IC50 of 16.97 ± 2.1 μM.
- Molecular dynamics confirmed stable binding of pentagalloyl glucose to the CgCdr1 protein.
Conclusions:
- Pentagalloyl glucose is identified as a novel inhibitor of CgCdr1.
- This natural compound shows significant potential as an antifungal agent against Candida glabrata.
- Further development of pentagalloyl glucose could lead to new treatments for invasive candidiasis.
