Role of theosaAgene inAspergillus fumigatusdevelopment, secondary metabolism and virulence

Abstract

AbstractAspergillus fumigatusis the leading cause of aspergillosis, associated with high mortality rates, particularly in immunocompromised individuals. In search of novel genetic targets against aspergillosis, we studied the WOPR transcription factor OsaA. Deletion of theosaAgene resulted in colony growth reduction. Conidiation is also influenced byosaA; bothosaAdeletion and overexpression resulted in a decrease in spore production. Wild-type expression levels ofosaAare necessary for expression of the conidiation regulatory genesbrlA,abaAandwetA. In addition,osaAis necessary for normal cell wall integrity. Furthermore, deletion ofosaAresulted in a reduction in the ability ofA. fumigatusto adhere to surfaces, decreased thermotolerance, as well as increased sensitivity to oxidative stress. Metabolomics analysis indicated thatosaAdeletion or overexpression led to alterations in the production of multiple secondary metabolites, including gliotoxin. This was accompanied by changes in the expression of genes in the corresponding secondary metabolite gene clusters. These effects could be, at least in part, due to the observed reduction in the expression levels of theveAandlaeAglobal regulators when theosaAlocus was altered. Importantly, our study shows thatosaAis indispensable for virulence in both the neutropenic and corticosteroid-immunosuppressed mouse models.