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Multidrug transporters of Candida species in clinical azole resistance

Rajendra Prasad1, Remya Nair1, Atanu Banerjee1

  • 1Amity Institute of Integrative Science and Health and Amity Institute of Biotechnology, Amity University Haryana, Gurgaon, Haryana, India.

Fungal Genetics and Biology : FG & B
|July 15, 2019
PubMed

Insights

Multidrug efflux pumps, like P-glycoprotein (P-gp), are key to antifungal resistance in Candida species. Overexpression of these transporters helps fungi survive azole treatments, posing challenges for immunocompromised patients.

Area of Science:

  • Mycology
  • Molecular Biology
  • Pharmacology

Background:

  • Multidrug resistance (MDR) is a significant challenge in treating opportunistic fungal infections, particularly in immunocompromised individuals.
  • Overexpression of efflux pumps, such as P-glycoprotein (P-gp), is a common mechanism for MDR in both cancer chemotherapy and antifungal treatments.
  • Candida species, including Candida albicans and non-albicans Candida (NAC) species, are leading causes of invasive fungal infections.

Purpose of the Study:

  • To summarize and discuss clinically relevant mechanisms of azole resistance in Candida species.
  • To highlight the critical role of multidrug efflux proteins in mediating antifungal resistance.
  • To provide insights into the challenges posed by azole-resistant fungal infections.

Main Methods:

  • Review of existing literature on azole resistance mechanisms in Candida species.
  • Focus on the role of efflux pump proteins belonging to the ABC and MFS superfamilies.
  • Analysis of clinical isolates exhibiting azole resistance.

Main Results:

  • Azole resistance in Candida species is significantly mediated by the overexpression of multidrug efflux pumps.
  • Efflux proteins from the ATP-binding cassette (ABC) and Major Facilitator Superfamily (MFS) are crucial for extruding azole drugs.
  • This efflux mechanism allows fungal cells to survive therapeutic azole concentrations.

Conclusions:

  • Multidrug efflux proteins are a primary mechanism of azole resistance in clinical isolates of Candida albicans and NAC species.
  • Understanding these efflux mechanisms is vital for developing strategies to overcome antifungal drug tolerance.
  • Targeting or circumventing these efflux pumps may improve the efficacy of azole-based therapies against Candida infections.
Keywords:
ABC superfamilyAzole resistanceCandida albicansMDR transportersMFS superfamilyNon-albicans Candida species

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