ena-STUDY-AALBORG UNIVERSITY-24-11-2020-14:08:27:435-770
Physiological responses of Aspergillus niger challenged with itraconazole
Aspergillus niger is an opportunistic pathogen commonly found in a variety of indoor and outdoor environments. Environmental isolates of A. niger taken from a pig farm were resistant to itracon-azole and in-depth investigations were conducted to better understand cellular responses during growth when exposed to an antifungal.       Using a combination of cultivation techniques, antibiotic stress-testing, and label-free prote-omics, this study has investigated the physiological and metabolic responses of A. niger to suble-thal levels of antifungal stress.       Challenging A. niger with itraconazole inhibited the growth, and the minimum inhibitory con-centration (MIC) was estimated to be >16 mg?L-1. Through the proteome analysis, 1305 unique proteins were identified. Differential expressed proteins during growth at 2 and 8 mg?L-1 itracona-zole revealed that a total of 91 and 50 proteins were significantly differentially expressed, respec-tively. Challenged with itraconazole, A. niger decreased the expression of peroxidative enzymes, increased the expression of an ATP-binding cassette (ABC) transporter most likely involved as an efflux pump, and inhibited ergosterol synthesis. Furthermore, a reduced expression of proteins involved in the production of ATP and reducing power from both TCA and glyoxylate cycle was ob-served. The mode of action of azoles in A. niger therefore appears more complex than previously anticipated and showcase future targets for antifungal treatment.
Aspergillus niger is an opportunistic pathogen commonly found in a variety of indoor and outdoor environments. Environmental isolates of A. niger taken from a pig farm were resistant to itracon-azole and in-depth investigations were conducted to better understand cellular responses during growth when exposed to an antifungal.       Using a combination of cultivation techniques, antibiotic stress-testing, and label-free prote-omics, this study has investigated the physiological and metabolic responses of A. niger to suble-thal levels of antifungal stress.       Challenging A. niger with itraconazole inhibited the growth, and the minimum inhibitory con-centration (MIC) was estimated to be >16 mg?L-1. Through the proteome analysis, 1305 unique proteins were identified. Differential expressed proteins during growth at 2 and 8 mg?L-1 itracona-zole revealed that a total of 91 and 50 proteins were significantly differentially expressed, respec-tively. Challenged with itraconazole, A. niger decreased the expression of peroxidative enzymes, increased the expression of an ATP-binding cassette (ABC) transporter most likely involved as an efflux pump, and inhibited ergosterol synthesis. Furthermore, a reduced expression of proteins involved in the production of ATP and reducing power from both TCA and glyoxylate cycle was ob-served. The mode of action of azoles in A. niger therefore appears more complex than previously anticipated and showcase future targets for antifungal treatment.