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

Krappmann S, Gabl E, Pazen T, Heizmann A, Pöggeler S, Krüger T, Kniemeyer O, Einsiedel J, Gmeiner P, Yu Y, Dyer PS, Baker SE, Nowrousian M (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Current Biology Elsevier (Cell Press)

DOI: 10.1016/j.cub.2025.03.080

Abstract

Members of the fungal kingdom serve as models for numerous cellular processes, among them sexuality.¹ In heterothallic ascomycetes, mating-type systems ensure that only compatible isolates fuse to enter the sexual phase.²^,³^,⁴^,⁵^,⁶ This includes reciprocal secretion and recognition of pheromones, commonly termed α-factor and a-factor, which are processed from peptide precursors.⁷^,⁸^,⁹^,¹⁰ Identification of fungal mating pheromones and their cognate receptors has been achieved by homology searches¹¹^,¹²^,¹³^,¹⁴^,¹⁵^,¹⁶^,¹⁷; however, this approach had failed to detect a-factor-like pheromones from Eurotiomycetes,⁵^,¹⁸^,¹⁹^,²⁰^,²¹ a fungal group including medically and economically important species.²² Sexuality of the opportunistic pathogen Aspergillus fumigatus²³^,²⁴^,²⁵ is genetically determined by a bipolar mating-type system encoding MAT1-1-1 and MAT1-2-1 regulators.¹⁶^,²⁶^,²⁷^,²⁸^,²⁹^,³⁰ By analyzing transcriptome data from strains overexpressing the corresponding MAT genes,³¹ 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 ppgBΔ 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 α-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.

Authors with CRIS profile

Sven Krappmann Professur für Klinische Mikrobiologie und Immunologie Tobias Pazen Institute of Microbiology – Clinical Microbiology, Immunology and Hygiene Anna Heizmann Department of Dermatology Jürgen Einsiedel Lehrstuhl für Pharmazeutische Chemie Peter Gmeiner Lehrstuhl für Pharmazeutische Chemie

Involved external institutions

Georg-August-Universität Göttingen

Germany (DE) Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie (Hans-Knöll-Institut (HKI)) / Leibniz Institute for Natural Product Research and Infection Biology

Germany (DE) Teikyo University

Japan (JP) University of Nottingham

United Kingdom (GB) Pacific Northwest National Laboratory

United States (USA) (US) Ruhr-Universität Bochum (RUB)

Germany (DE)

How to cite

APA:

Krappmann, S., Gabl, E., Pazen, T., Heizmann, A., Pöggeler, S., Krüger, T.,... 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

MLA:

Krappmann, Sven, et al. "Identification of an a-factor-like pheromone secreted by the heterothallic ascomycete Aspergillus fumigatus." Current Biology (2025).

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