The mtfA Transcription Factor Gene Controls Morphogenesis, Gliotoxin Production, and Virulence in the Opportunistic Human Pathogen Aspergillus fumigatus

Aspergillus fumigatus is the leading causative agent of invasive aspergillosis (IA). The number of cases is on the rise, with mortality rates as high as 90% among immunocompromised patients. Molecular genetic studies inA. fumigatus could provide novel targets to potentially set the basis for antifungal therapies. In the current study, we investigated the role of the transcription factor genemtfA inA. fumigatus . Our results revealed thatmtfA plays a role in the growth and development of the fungus. Deletion or overexpression ofmtfA leads to a slight reduction in colony growth, as well as a reduction in conidiation levels, in the overexpression strain compared to the wild-type strain. Furthermore, production of the secondary metabolite gliotoxin increased whenmtfA was overexpressed, coinciding with an increase in the transcription levels of the gliotoxin genesgliZ andgliP with respect to the wild type. In addition, our study showed thatmtfA is also necessary for normal protease activity inA. fumigatus ; deletion ofmtfA resulted in a reduction of protease activity compared to wild-type levels. Importantly, the absence ofmtfA caused a decrease in virulence in theGalleria mellonella infection model, indicating thatmtfA is necessary forA. fumigatus wild-type pathogenesis.