All about CDR transporters: Past, present, and future

Area of Science:

• Mycology
• Molecular Biology
• Antimicrobial Resistance

Background:

• Human pathogenic Candida species exhibit evolving drug resistance mechanisms.
• These fungi employ diverse strategies to overcome antifungal drugs, posing significant health threats.
• Established resistance includes target alteration and overexpression; novel mechanisms involve altered drug permeability.

Purpose of the Study:

• To review the evolving drug resistance mechanisms in Candida species.
• To emphasize the role of drug efflux transporters in conferring multidrug resistance.
• To discuss the impact of these findings on antifungal research and susceptibility determination.

Main Methods:

• Literature review of studies on Candida drug resistance.
• Analysis of genetic and molecular mechanisms of drug efflux.
• Examination of the role of specific genes like CDR1 in resistance.

Main Results:

• Candida species utilize permeability constraints, particularly increased drug efflux, to resist antifungals.
• Candida drug resistance genes encode membrane efflux transporters that expel drugs.
• Reduced azole permeability due to efflux is a key factor in antifungal susceptibility.

Conclusions:

• Drug efflux transporters are critical determinants of antifungal resistance in Candida.
• The discovery of efflux genes has reshaped antifungal research paradigms.
• Understanding these mechanisms is vital for developing effective antifungal therapies.