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Updated: Feb 27, 2026
Bio-energetics Investigation of Candida albicans Using Real-time Extracellular Flux Analysis
Published on: March 19, 2019
Functional analysis of selected deletion mutants in Candida glabrata under hypoxia
Payal Gupta1, Ramesh Chand Meena2, Navin Kumar3
1Department of Biotechnology, Graphic Era University, 566/6, Bell Road, Clement Town, Dehradun, Uttarakhand, 248002, India.
Abstract:
Increased drug resistance in Candida glabrata (a model non-albicans Candida) calls for the identification of potential molecular targets for the development of effective drugs. Hypoxia (a state of low oxygen) is an important host factor, which affects the virulence of the pathogen and efficacy of drugs. In the present study, in vitro characterization of 13 null mutants of C. glabrata were done under hypoxic condition (1% O2). These mutants have a major role to play in cellular pathways, viability and pathogenesis (cell wall biosynthesis, ergosterol synthesis, calcium-calcineurin, etc.). The in vitro growth, biofilm formation and susceptibility of biofilm to antifungal drugs of these mutants were compared with the control. Hypoxia reduced the susceptibility of planktonic cells to fluconazole. The mutants ecm33Δ, kre1Δ, rox1Δ, and kre2Δ showed maximum reductions in their biofilm activities (>20%). The selected mutants (upc2BΔ, kre2 Δ, ecm7Δ, rox1 Δ, mid1Δ, ecm33Δ, cch1Δ, kre1Δ) showed reduced biofilm activities (>30%) in the presence of 16 μg ml-1 fluconazole under hypoxia. Functional analysis revealed that Kre1, Ecm33, Upc2B, Kre2, Ecm7, Cch1, Mid1 and Rox1 can be explored as a potential drug target for developing novel antifungal drugs.
Insights
Drug resistance in Candida glabrata is a growing concern. Researchers identified key molecular targets, including Kre1 and Ecm33, that could lead to new antifungal drugs effective even under low-oxygen conditions.
Area of Science:
- Medical Mycology
- Molecular Biology
- Drug Discovery
Background:
- Candida glabrata exhibits increasing drug resistance, necessitating new therapeutic targets.
- Hypoxia, a low-oxygen environment, influences pathogen virulence and drug effectiveness.
- Understanding C. glabrata's response to hypoxia is crucial for developing novel antifungal strategies.
Purpose of the Study:
- To investigate the role of specific C. glabrata mutants in virulence and drug susceptibility under hypoxic conditions.
- To identify potential molecular targets for new antifungal drug development.
Main Methods:
- In vitro characterization of 13 null mutants of C. glabrata under 1% oxygen (hypoxia).
- Assessment of in vitro growth, biofilm formation, and antifungal susceptibility of mutants compared to controls.
- Evaluation of mutant biofilm activity in the presence of fluconazole under hypoxia.
Main Results:
- Hypoxia decreased planktonic cell susceptibility to fluconazole.
- Mutants ecm33Δ, kre1Δ, rox1Δ, and kre2Δ showed significant reductions in biofilm formation (>20%).
- Several mutants (upc2BΔ, kre2Δ, ecm7Δ, rox1Δ, mid1Δ, ecm33Δ, cch1Δ, kre1Δ) exhibited reduced biofilm activity (>30%) with fluconazole under hypoxia.
Conclusions:
- Proteins Kre1, Ecm33, Upc2B, Kre2, Ecm7, Cch1, Mid1, and Rox1 are potential drug targets.
- These targets may be crucial for C. glabrata pathogenesis and biofilm formation under hypoxic conditions.
- Targeting these pathways could lead to the development of novel antifungal therapies against drug-resistant strains.
