Identification of an a-factor-like pheromone secreted by the heterothallic ascomycete Aspergillus fumigatus

Krappmann, Sven; Gabl, Elisabeth; Pazen, Tobias; Heizmann, Anna; Pöggeler, Stefanie; Krüger, Thomas; Kniemeyer, Olaf; Einsiedel, Jürgen; Gmeiner, Peter; Yu, Yidong; Dyer, Paul S.; Baker, Scott E.; Nowrousian, Minou

Abstract

Members of the fungal kingdom serve as models for numerous cellular processes, among them sexuality. In heterothallic ascomycetes, mating-type systems ensure that only compatible isolates fuse to enter the sexual phase. This includes reciprocal secretion and recognition of pheromones, commonly termed a-factor and a-factor, which are processed from peptide precursors. Identification of fungal mating pheromones and their cognate receptors has been achieved by homology searches; however, this approach had failed to detect a-factor-like pheromones from Eurotiomycetes, a fungal group including medically and economically important species. Sexuality of the opportunistic pathogen Aspergillus fumigatus is genetically determined by a bipolar mating-type system encoding MAT1-1-1 and MAT1-2-1 regulators. By analyzing transcriptome data from strains overexpressing the corresponding MAT genes, we identified a candidate pheromone precursor gene B (ppgB) to encode the elusive Eurotiomycete a-factor pheromone. Its deduced peptide is 24 aa in length and features a canonical CaaX farnesylation motif. Further analyses provided supporting evidence that PpgB is a prototype for the a-factor-like pheromone of the aspergilli, including expression of ppgB in a MAT1-2-1-dependent manner, and that an A. fumigatus ppgBD deletion strain was unable to mate and form fruiting bodies with a compatible partner. Inspection of Aspergillus genomes from members of the section Fumigati revealed high conservation of PpgB sequence as well as of the a-factor-like PpgA, indicating that incompatibility factors other than solely pheromone discrimination are responsible for speciation. The identification of the A. fumigatus a-factor-like pheromone closes a substantial knowledge gap with respect to cellular recognition and sexual propagation of Eurotiomycete fungi.

Citation

Krappmann, S., Gabl, E., Pazen, T., Heizmann, A., Pöggeler, S., Krüger, T., Kniemeyer, O., Einsiedel, J., Gmeiner, P., Yu, Y., Dyer, P. S., Baker, S. E., & Nowrousian, M. (2025). Identification of an a-factor-like pheromone secreted by the heterothallic ascomycete Aspergillus fumigatus. Current Biology, https://doi.org/10.1016/j.cub.2025.03.080

• Journal Article Type: Article
• Acceptance Date: Mar 31, 2025
• Online Publication Date: Apr 21, 2025
• Publication Date: Apr 21, 2025
• Deposit Date: Apr 28, 2025
• Publicly Available Date: Apr 29, 2025
• Journal: Current Biology
• Print ISSN: 0960-9822
• Electronic ISSN: 1879-0445
• Publisher: Cell Press
• Peer Reviewed: Peer Reviewed
• DOI: https://doi.org/10.1016/j.cub.2025.03.080
• Public URL: https://nottingham-repository.worktribe.com/output/48353639
• Publisher URL: https://www.cell.com/current-biology/fulltext/S0960-9822(25)00427-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0960982225004270%3Fshowall%3Dtrue
• Additional Information: This article is maintained by: Elsevier; Article Title: Identification of an a-factor-like pheromone secreted by the heterothallic ascomycete Aspergillus fumigatus; Journal Title: Current Biology; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.cub.2025.03.080; Content Type: article; Copyright: © 2025 The Authors. Published by Elsevier Inc.