Autocrine pheromone signalling regulates community behaviour in the fungal pathogen Fusarium oxysporum

Abstract

Autocrine self-signalling via secreted peptides and cognate receptors regulates cell development in eukaryotes and is conserved from protozoans to mammals1,2. In contrast, secreted peptides from higher fungi have been traditionally associated with paracrine non-self-signalling during sexual reproduction3. For example, cells of the model fungus Saccharomyces cerevisiae fall into two distinct mating types (MAT), which produce either a- or α-pheromone and the cognate receptors Ste2 or Ste3, respectively4. Inappropriate autocrine pheromone signalling (APS) during mating is prevented by downregulation of the self-pheromone receptor4,5 and by a-type cell-specific cleavage of α-pheromone through the protease Bar1 (refs. 6,7,8). While APS can be artificially induced by manipulation of the pheromone secrete-and-sense circuit7,9,10,11, its natural occurrence in ascomycete fungi has not been described. Here, we show that Fusarium oxysporum—a devastating plant pathogen that lacks a known sexual cycle12—co-expresses both pheromone–receptor pairs, resulting in autocrine regulation of developmental programmes other than mating. We found that unisexual populations of MAT1-1 cells (α-type idiomorphs13) secrete and sense both a- and α-pheromone, and that their perception requires the cognate receptors and conserved elements of the cell wall integrity mitogen-activated protein kinase cascade. We further show that F. oxysporum uses APS to regulate spore germination in a cell-density-dependent manner, whereby the α-Ste2 interaction leads to repression of conidial germination while the a-Ste3 interaction relieves repression. Our results reveal the existence of a regulatory function for peptide pheromones in the quorum-sensing-mediated control of fungal development.

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Fig. 1: Pheromone discrimination is controlled by Bar1 activity and Ste2/Ste3 receptor abundance.
Fig. 2: F. oxysporum MAT1-1 cells secrete and sense both a- and α-pheromone.
Fig. 3: α-pheromone causes cell-density-dependent repression of conidial germination via the CWI MAPK cascade.
Fig. 4: a-pheromone quenches α-pheromone-mediated repression of conidial germination.

Data availability

All data that support the findings of this study are either included in this published article and its Supplementary Information files, or available from the corresponding author upon request. F. oxysporum gene data are available in GenBank under the following accession numbers: MFa (a-pheromone precursor), FOXG_18106; MFα (α-pheromone precursor), FOXG_08636; ste3, FOXG_02147; ste2, FOXG_10633; bar1, FOXG_09428; fmk1, FOXG_08140; ste12, FOXG_02103; rho1, FOXG_13835; bck1, FOXG_08078; mkk2, FOXG_02117; mpk1, FOXG_05092.

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Acknowledgements

We thank the members of the Di Pietro laboratory for helpful comments on the manuscript, and E. Martínez Aguilera for valuable technical assistance. This work was supported by grant BIO2016-78923-R from the Spanish Ministerio de Economía y Competitividad to A.D.P. S.V. was supported by the Marie Curie ITN FungiBrain (FP7-PEOPLE-ITN-607963).

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S.V., D.T. and A.D.P. designed the experiments. S.V. and D.T. carried out the experiments. S.V. and D.T. analysed the data. S.V., A.D.P. and D.T. wrote the manuscript.

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Correspondence to David Turrà.

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Supplementary information

Supplementary Information

Supplementary Figs. 1–12, Table 3 and references.

Reporting Summary

Supplementary Table 1

Complete list of P values for all statistical analyses.

Supplementary Table 2

Oligonucleotide primers used in this study.

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Vitale, S., Di Pietro, A. & Turrà, D. Autocrine pheromone signalling regulates community behaviour in the fungal pathogen Fusarium oxysporum. Nat Microbiol 4, 1443–1449 (2019). https://doi.org/10.1038/s41564-019-0456-z

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