Leveraging synthetic genetic array screening to identify therapeutic targets and inhibitors for combatting azole resistance in Candida glabrata

Abstract

Candida glabrata is a significant cause of life-threatening fungal infections, especially concerning due to its rapid development of resistance to commonly used antifungal drugs like azoles. The growing prevalence of multi-drug-resistant C. glabrata strains, coupled with their high mortality rate, underscores the urgency of identifying new treatment strategies. This study investigates the genetic mechanisms underlying drug resistance, specifically focusing on mutations in the CgPDR1 gene, which increase azole resistance. By leveraging a novel genetic screening method, this work identifies genes that interact with drug-resistant mutations, offering potential new therapeutic targets. Additionally, an inhibitor identified through in silico screening shows promise in delaying azole resistance when tested in vitro . The findings highlight the potential of multi-target therapies to combat drug resistance, paving the way for more effective treatment options for C. glabrata infections and addressing an urgent clinical need.