Understanding adaptation to fluconazole: comparative insights into tolerance and resistance in and .

Introduction: Antifungal resistance and tolerance are distinct responses exhibited by fungi when exposed to drugs. While considerable research has focused on azole tolerance in the human pathogen , studies in other fungal species remain limited.

Objective: This study aims to conduct a comparative investigation of the adaptation of the model organism and to fluconazole .

Methods: We performed experiments using laboratory strains of and to evaluate their fluconazole tolerance and resistance under varying temperature conditions. High concentrations of fluconazole were administered, and subsequent changes in fungal phenotypes were analyzed through techniques such as transcriptome analysis and monitoring of petite formation.

Results: Our results revealed that fluconazole tolerance is present in wild-type strains of and is influenced by temperature, albeit in a manner opposite to that observed in . Importantly, when subjected to high concentrations of fluconazole, strains developed resistance without displaying tolerance; all resistant adaptors identified were petites. Chemical induction of petite formation led to an increase in resistance accompanied by a decrease in tolerance.

Conclusion: Transcriptome analysis indicated that petites up-regulated efflux mechanisms while down-regulating most genes. This suggests that, unlike petite-negative , petite-positive swiftly transitions to a petite phenotype upon exposure to fluconazole, resulting in enhanced resistance but diminished tolerance. This evolutionary divergence emphasizes the need for additional studies on fluconazole tolerance in other pathogenic fungi.