Physiological Responses of Aspergillus Niger Challenged with Itraconazole

is an opportunistic pathogen commonly found in a variety of indoor and outdoor environments. An environmental isolate of from a pig farm was resistant to itraconazole, and in-depth investigations were conducted to better understand cellular responses that occur during growth when this pathogen is exposed to an antifungal. Using a combination of cultivation techniques, antibiotic stress testing, and label-free proteomics, this study investigated the physiological and metabolic responses of to sublethal levels of antifungal stress. Challenging with itraconazole inhibited growth, and the MIC was estimated to be > 16 mg · liter Through the proteome analysis, 1,305 unique proteins were identified. During growth with 2 and 8 mg · liter itraconazole, a total of 91 and 50 proteins, respectively, were significantly differentially expressed. When challenged with itraconazole, exhibited decreased expression of peroxidative enzymes, increased expression of an ATP-binding cassette (ABC) transporter most likely involved as an azole efflux pump, and inhibited ergosterol synthesis; however, several ergosterol biosynthesis proteins increased in abundance. Furthermore, reduced expression of proteins involved in the production of ATP and reducing power from both the tricarboxylic acid (TCA) and glyoxylate cycles was observed. The mode of action of triazoles in therefore appears more complex than previously anticipated, and these observations may help highlight future targets for antifungal treatment.