Related Experiment Video

Updated: Jun 19, 2026

Whole Genome Sequencing of Candida glabrata for Detection of Markers of Antifungal Drug Resistance
08:45

Whole Genome Sequencing of Candida glabrata for Detection of Markers of Antifungal Drug Resistance

Published on: December 28, 2017

13.9K

Zap1 is required for Candida glabrata response to fluconazole

A Gaspar-Cordeiro1, G Afonso1, C Amaral1

  • 1Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. República, 2780-157 Oeiras, Portugal.

FEMS Yeast Research
|January 18, 2022
PubMed

Insights

Zap1 regulates fluconazole resistance in Candida glabrata by affecting drug accumulation and membrane composition. Deleting Zap1 increases fluconazole sensitivity due to lower ergosterol and altered phospholipids.

Area of Science:

  • Mycology
  • Molecular Biology
  • Antifungal Resistance

Background:

  • Fluconazole resistance in Candida species is a growing clinical challenge.
  • Understanding fungal responses to antifungals is crucial for developing new therapies.

Purpose of the Study:

  • To investigate the role of Zap1 in Candida glabrata's response to fluconazole.
  • To elucidate the mechanisms underlying Zap1-mediated fluconazole resistance.

Main Methods:

  • Gene deletion studies (CgΔzap1 mutant).
  • Measurement of intracellular fluconazole accumulation.
  • Analysis of ergosterol and membrane phospholipid composition.
  • Gene expression analysis of drug efflux transporters (CDR1) and regulators (PDR1).

Main Results:

  • Candida glabrata cells lacking Zap1 (CgΔzap1) accumulate higher levels of fluconazole.
  • Zap1 deletion correlates with reduced ergosterol levels and altered membrane phospholipid composition.
  • Zap1 acts as a negative regulator of the drug efflux transporter gene CDR1 and its regulator PDR1.
  • Impaired membrane function in Zap1-depleted cells likely contributes to increased fluconazole sensitivity.

Conclusions:

  • Zap1 plays a significant role in Candida glabrata's response to fluconazole, extending beyond zinc homeostasis.
  • Zap1 influences drug accumulation and membrane integrity, impacting fluconazole efficacy.
  • Targeting Zap1 or its associated pathways could offer novel strategies to combat fluconazole-resistant Candida infections.
Keywords:
Cdr1Pdr1Zap1drug effluxfluconazoleyeast

More Related Videos

Small-Scale Plasma Membrane Preparation for the Analysis of Candida albicans Cdr1-mGFPHis09:44

Small-Scale Plasma Membrane Preparation for the Analysis of Candida albicans Cdr1-mGFPHis

Published on: June 13, 2021

2.8K
Author Spotlight: Photodynamic Therapy as a Novel Approach to Induce Petite Colonies in Drug-Resistant Candida for Antifungal Research09:06

Author Spotlight: Photodynamic Therapy as a Novel Approach to Induce Petite Colonies in Drug-Resistant Candida for Antifungal Research

Published on: March 29, 2024

831

Related Concept Videos

Cryptococcal Meningitis01:27

Cryptococcal Meningitis

Cryptococcal meningitis is a life-threatening opportunistic infection predominantly associated with HIV/AIDS, accounting for over 100,000 deaths annually worldwide. However, it also affects individuals with other forms of immunosuppression, including those undergoing immunosuppressive therapy, organ transplant recipients, patients with innate immunodeficiencies, and individuals with hematological disorders. The infection is caused mainly by Cryptococcus neoformans and Cryptococcus gattii,...
Candidiasis01:20

Candidiasis

Candidiasis is a fungal infection caused by opportunistic species of Candida. It can affect various anatomical sites, including the skin, oral cavity, nails, and genitourinary tract. Among its forms, vaginal candidiasis is the most common type of mucosal infection. It typically results from the overgrowth of Candida albicans in the vaginal mucosa. Under normal conditions, C. albicans exists as a commensal organism within the vaginal microbiota, regulated by the dominance of lactobacilli, which...
Antifungal Agents01:15

Antifungal Agents

Amphotericin B is a broad-spectrum antifungal agent that exploits structural differences between fungal and mammalian cell membranes. Its amphipathic structure—featuring a hydrophobic polyene-lactone ring and a hydrophilic region containing mycosamine and carboxylic acid groups—enables selective binding to ergosterol, a sterol predominantly found in fungal plasma membranes. This selective interaction underlies the drug’s antifungal activity, although weak binding to cholesterol contributes to...