真菌耐药机制中的染色体非整倍体现象研究进展OA

Fungal drug-resistance poses a serious threat to global public health,with mechanisms encompassing genetic mutations,epigenetic regulation,and genomic instability.Chromosomal aneuploidy has recently emerged as a critical driver of resistance.This review comprehensively summarizes the molecular mechanisms by which aneuploidy mediates resistance in pathogenic fungi,including gene dosage effects,transcriptional dysregulation,and metabolic pathway interference.Key findings reveal that Candida albicans upregulates efflux pump genes(CDR1/2)through chromosomal duplication,while Aspergillus fumigatus reduces azole susceptibility via cyp51A copy number amplification.In Cryptococcus neoformans,stress-induced aneuploidy exhibits dynamic plasticity,rapidly emerging under drug pressure and reverting upon withdrawal.Technologies such as whole genome sequencing(WGS)and qPCR have proven pivotal to be for clinical resistance prediction and therapeutic monitoring,yet cost and technical barriers hinder their widespread implementation.Future research should focus on deciphering the interplay between aneuploidy,epigenetic modifications,and mutational accumulation,alongside developing therapeutic strategies to correct aneuploidy and optimize rapid diagnostics for precision of medicine application.By synthesizing cross-species evidence,this review advances our understanding of fungal resistance mechanisms and informs the development of novel interventions.