The Transcriptional Regulator HbxA Governs Development, Secondary Metabolism, and Virulence in Aspergillus fumigatus.

is the leading cause of invasive aspergillosis, which in immunocompromised patients results in a mortality rate as high as 90%. Earlier studies showed that HbxA is a global regulator in affecting morphological development and secondary metabolism. Here, we determined its role in , examining whether HbxA influences the regulation of asexual development, natural product biosynthesis, and virulence of this fungus. Our analysis demonstrated that removal of the gene caused a near-complete loss of conidial production in the mutant strain, as well as a slight reduction in colony growth. Other aspects of asexual development are affected, such as size and germination of conidia. Furthermore, we showed that in , the loss of decreased the expression of the central regulatory pathway involved in asexual development, as well as the expression of the "fluffy" genes , , and HbxA was also found to regulate secondary metabolism, affecting the biosynthesis of multiple natural products, including fumigaclavines, fumiquinazolines, and chaetominine. In addition, using a neutropenic mouse infection model, was found to negatively impact the virulence of The number of immunodepressed individuals is increasing, mainly due to the greater life expectancy in immunodepressed patients due to improvements in modern medical treatments. However, this population group is highly susceptible to invasive aspergillosis. This devastating illness, mainly caused by the fungus , is associated with mortality rates reaching 90%. Treatment options for this disease are currently limited, and a better understanding of genetic regulatory mechanisms is paramount for the design of new strategies to prevent or combat this infection. Our work provides new insight into the regulation of the development, metabolism, and virulence of this important opportunistic pathogen. The transcriptional regulatory gene has a profound effect on biology, governing multiple aspects of conidial development. This is relevant since conidia are the main source of inoculum in infections. Importantly, also regulates the biosynthesis of secondary metabolites and the pathogenicity of this fungus.