Cdr1 in focus: a personal reflection on multidrug transporter research.

Drug resistance mechanisms in human pathogenic Candida species are constantly evolving. Over time, these species have developed diverse strategies to counter the effects of various drug classes, making them a significant threat to human health. In addition to well-known mechanisms such as drug target modification, overexpression, and chromosome duplication, Candida species have also developed permeability barriers to antifungal drugs through reduced drug import or increased efflux. The genomes of Candida species contain a multitude of drug resistance genes, many of which encode membrane efflux transporters that actively expel drugs, preventing their toxic accumulation inside the cells and contributing to multidrug resistance. This brief personal retrospective piece for the "Thematic Issue on Celebrating 30 Years of Cdr1 Research: new trends in antifungal therapy and drug resistance" looks back as to how antifungal research has shifted focus since the identification of the first multidrug transporter gene, CDR1 (Candida Drug Resistance 1), leading to new insights into how reduced azole permeability across Candida cell membranes influences antifungal susceptibility.