Long-noncoding RNAafu-182- A novel regulator of fungal triazole tolerance

Invasive infections related to the saprophytic mold Aspergillus fumigatus are on the rise, and drug resistance often exacerbates the problem. The mechanisms of fungal adaptation to the azole drugs are not clear. Recently, it has been shown that A. fumigatus can form persistent colonies in response to azole drugs. Long non-coding (lnc)RNAs have been associated with stress adaptation that may eventually lead to resistance. This research team has identified a lncRNA, afu-182, that acts as a negative regulator of azole tolerance. This project will now use innovative approaches to identify the role(s) of afu-182 and delineate the azole response network in A. fumigatus. Aim 1 will characterize the roles of the RTM family of proteins, a class of protein that is involved in ameliorating xenobiotic stress, and define their regulation by afu-182. Aim 2 will study the structure-function relationship of afu-182 to understand the mechanistic basis of afu-182 action. Aim 3 will study a closely related homothallic fungus, Aspergillus nidulans, with a short, defined sexual cycle in an unbiased forward-genetics approach to identify novel factors in azole response. Using a new fundamental paradigm of study, this project will determine the novel mechanisms of azole response in Aspergilli, which will eventually reveal new strategies to combat the rise of azole drug resistance. Project Number: 1R01AI189831-01A1 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Allergy and Infectious Diseases (NIAID) | Principal Investigator: Sourabh Dhingra | Institution: CLEMSON UNIVERSITY, CLEMSON, SC | Award Amount: $418,378 | Activity Code: R01 | Study Section: Anti-Infective Resistance and Targets Study Section [AIRT] View on NIH RePORTER: https://reporter.nih.gov/project-details/1R01AI18983101A1