Experimental and in-host evolution of triazole resistance in human pathogenic fungi

The leading fungal pathogens causing systemic infections in humans are Candida spp., Aspergillus fumigatus , and Cryptococcus neoformans . major class of antifungals used to treat such the triazoles, which target cytochrome P450 lanosterol 14-α-demethylase, encoded by ERG11 (yeasts)/ cyp51A (molds) genes, catalyzing a key step ergosterol biosynthetic pathway. Triazole resistance clinical fungi is rising concern worldwide, increasing mortality immunocompromised patients. This review describes use serial isolates in-vitro evolution toward understanding mechanisms triazole resistance. We outline, compare, discuss how these approaches have helped identify evolutionary pathways taken pathogenic acquire While they all share core mechanism (mutation overexpression ERG11/cyp51A efflux transporters), their timing differs: spp. exhibit resistance-conferring aneuploidies copy number variants not seen A. proclivity develop undergoing mutations transcription factors ( TAC1, MRR1, PDR5 ) that increase expression transporters. especially prone accumulate early during Recently, examination experimental lab-evolved triazole-resistant strains using modern omics gene editing tools has begun realize full potential approaches. As result, triazole-resistance can now be analyzed at increasingly finer resolutions. newfound knowledge will instrumental formulating new molecular fight rapidly emerging epidemic antifungal resistant fungi.