Systematic gene deletion and functional characterization of histidine kinase phosphorelay receptors (HKRs) in the human pathogenic fungus Aspergillus fumigatus

• Our study gained new important insights into the role of HKRs in physiology of A. fumigatus.
• NikA/TcsC could be involved in the cell wall integrity pathway.
• Fhk6 and PhkA could be involved in the regulation of the “fluffy” developmental program.
• PhkA and PhkB could be involved in the regulation of conidiation.
• PhkA could be involved in the resistance of oxidative stresses.

Histidine kinase receptors (HKRs) appear to be a common strategy for model and pathogenic fungi to sense and respond to environmental stresses. In the human pathogen Aspergillus fumigatus, which is responsible for invasive aspergillosis, 13 genes potentially encoding HKRs have been identified. Until now, only three HKRs have been functionally characterized. The aim of this study was to perform the systematic invalidation of A. fumigatus HKR genes and the careful phenotypic characterization of the relevant mutants. This study notably allowed to gain new important insights into the role of HKRs in physiology of A. fumigatus. Actually, we showed that (i) NikA/TcsC could be involved in the cell wall integrity pathway, (ii) Fhk6 and PhkA were involved in the regulation of the “fluffy” developmental program, (iii) PhkB could participate in the regulation of conidiation and (iv) PhkA was implied in the resistance of oxidative stresses.