MybA, a transcription factor involved in conidiation and conidial viability of the human pathogen Aspergillus fumigatus

5 years ago

MybA, a transcription factor involved in conidiation and conidial viability of the human pathogen Aspergillus fumigatus

Marie-Christine Prevost, Paul Carr, Oumaima Ibrahim-Granet, Adeline Mallet, Jae-Hyuk Yu, John Gibbons, Jacomina Krijnse-Locker, Laetitia Muszkieta, Jean Paul Latgé, Vishukumar Aimanianda, Antonis Rokas, Joanne Wong Sak Hoi, Özgür Bayram, Cosmin Saveanu, Isabel Valsecchi, Gerhard H Braus, Özlem Sarikaya-Bayram, Michael Bromley, Isabelle Mouyna

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. A new key regulator of conidiogenesis with a Myb DNA binding motif has been identified in the human fungal pathogen Aspergillus fumigatus. MybA protein functions upstream of wetA, vosA and velB, the key regulators involved in conidial maturation but is not associated with the key transcription factors brlA and abaA controlling the conidiogenesis in Aspergillus. MybA controls the expression of enzymes involved in trehalose, cell wall biosynthesis and ROS scavenging enzymes controlling the conidial maturation and dormancy.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/mmi.13744