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Valsecchi I;Sarikaya-Bayram Ö;Wong Sak Hoi J;Muszkieta L;Gibbons J;Prevost MC;Mallet A;Krijnse-Locker J;Ibrahim-Granet O;Mouyna I;Carr P;Bromley M;Aimanianda V;Yu JH;Rokas A;Braus GH;Saveanu C;Bayram Ö;Latgé JP;
Molecular Microbiology
MybA, a transcription factor involved in conidiation and conidial viability of the human pathogen Aspergillus fumigatus.
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Aspergillus fumigatus, a ubiquitous human fungal pathogen, produces asexual spores (conidia), which are the main mode of propagation, survival and infection of this human pathogen. In this study, we present the molecular characterization of a novel regulator of conidiogenesis and conidial survival called MybA because the predicted protein contains a Myb DNA binding motif. Cellular localization of the MybA::Gfp fusion and immunoprecipitation of the MybA::Gfp or MybA::3xHa protein showed that MybA is localized to the nucleus. RNA sequencing data and a uidA reporter assay indicated that the MybA protein functions upstream of wetA, vosA and velB, the key regulators involved in conidial maturation. The deletion of mybA resulted in a very significant reduction in the number and viability of conidia. As a consequence, the ΔmybA strain has a reduced virulence in an experimental murine model of aspergillosis. RNA-sequencing and biochemical studies of the ΔmybA strain suggested that MybA protein controls the expression of enzymes involved in trehalose biosynthesis as well as other cell wall and membrane-associated proteins and ROS scavenging enzymes. In summary, MybA protein is a new key regulator of conidiogenesis and conidial maturation and survival, and plays a crucial role in propagation and virulence of A. fumigatus.
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