Aspergillus fumigatus is a fungal pathogen that makes up 90% of all Aspergillus-related infections, and can be debilitating and fatal in immunocompromised patients. However, current drug treatment options have limited effectiveness. A potential drug target is Acetohydroxyacid synthase (AHAS; EC 2.2.1.6), which is the first enzyme in the amino acid biosynthesis pathway that has been the target of development for over 50 commercial herbicides from five different families. In this study, the effects of these commercial herbicides was investigated as a potential antifungal treatment option. We expressed, purified and characterised A. fumigatus AHAS and determined the inhibitory effects of six herbicides from two herbicide families.
The most potent herbicide has a kiapp (apparent first order rate of enzyme inactivation) of 18.54 ± 2.588 min-1, k3 (rate of enzyme recovery) of 0.012 min-1, and a Ki of 1.8 ± 0.92 nM. This herbicide can also inhibit A. fumigatus cell growth at a minimum inhibitory concentration (MIC) value of 15.53 µg/mL with fungicidal effects. The results demonstrate that this compound has potential to be developed as an antifungal agent to combat A. fumigatus infections.