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


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.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

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.


  1. 1.

    Doğaner, B. A., Yan, L. K. Q. & Youk, H. Autocrine signaling and quorum sensing: extreme ends of a common spectrum. Trends Cell Biol. 26, 262–271 (2016).

    Article  Google Scholar 

  2. 2.

    Vallesi, A., Giuli, G., Bradshaw, R. A. & Luporini, P. Autocrine mitogenic activity of pheromones produced by the protozoan ciliate Euplotes raikovi. Nature 376, 522–524 (1995).

    CAS  Article  Google Scholar 

  3. 3.

    Arkowitz, R. A. Chemical gradients and chemotropism in yeast. Cold Spring Harb. Perspect. Biol. 1, a001958 (2009).

    Article  Google Scholar 

  4. 4.

    Lee, S. C., Ni, M., Li, W., Shertz, C. & Heitman, J. The evolution of sex: a perspective from the fungal kingdom. Microbiol. Mol. Biol. Rev. 74, 298–340 (2010).

    CAS  Article  Google Scholar 

  5. 5.

    Herskowitz, I., Rine, J. & Strathern, J. in The Molecular and Cellular Biology of the Yeast Saccharomyces (eds Jones, E. W., Pringle, J. R. & Broach, J. R.), 583–656 (Cold Spring Harbor, 1992).

  6. 6.

    Hicks, J. B. & Herskowitz, I. Evidence for a new diffusible element of mating pheromones in yeast. Nature 260, 246–248 (1976).

    CAS  Article  Google Scholar 

  7. 7.

    Alby, K., Schaefer, D. & Bennett, R. J. Homothallic and heterothallic mating in the opportunistic pathogen Candida albicans. Nature 460, 890–893 (2009).

    CAS  Article  Google Scholar 

  8. 8.

    Ladds, G., Rasmussen, E. M., Young, T., Nielsen, O. & Davey, J. The sxa2-dependent inactivation of the P-factor mating pheromone in the fission yeast Schizosaccharomyces pombe. Mol. Microbiol. 20, 35–42 (1996).

    CAS  Article  Google Scholar 

  9. 9.

    Kitamura, K., Nakamura, T., Miki, F. & Shimoda, C. Autocrine response of Schizosaccharomyces pombe haploid cells to mating pheromones. FEMS Microbiol. Lett. 143, 41–45 (1996).

    CAS  Article  Google Scholar 

  10. 10.

    Youk, H. & Lim, W. A. Secreting and sensing the same molecule allows cells to achieve versatile social behaviors. Science 343, 1242782 (2014).

    Article  Google Scholar 

  11. 11.

    Dudin, O., Merlini, L. & Martin, S. G. Spatial focalization of pheromone/MAPK signaling triggers commitment to cell–cell fusion. Genes Dev. 30, 2226–2239 (2016).

    CAS  Article  Google Scholar 

  12. 12.

    Dean, R. et al. The top 10 fungal pathogens in molecular plant pathology. Mol. Plant Pathol. 13, 414–430 (2012).

    Article  Google Scholar 

  13. 13.

    Martin, T. et al. Tracing the origin of the fungal α1 domain places its ancestor in the HMG-box superfamily: implication for fungal mating-type evolution. PLoS ONE 5, e15199 (2010).

    Article  Google Scholar 

  14. 14.

    Yi, S. et al. Self-induction of a/a or α/α biofilms in Candida albicans is a pheromone-based paracrine system requiring switching. Eukaryot. Cell 10, 753–760 (2011).

    CAS  Article  Google Scholar 

  15. 15.

    Turra, D., Nordzieke, D., Vitale, S., El Ghalid, M. & Di Pietro, A. Hyphal chemotropism in fungal pathogenicity. Semin. Cell Dev. Biol. 57, 69–75 (2016).

    CAS  Article  Google Scholar 

  16. 16.

    Turra, D., El Ghalid, M., Rossi, F. & Di Pietro, A. Fungal pathogen uses sex pheromone receptor for chemotropic sensing of host plant signals. Nature 527, 521–524 (2015).

    CAS  Article  Google Scholar 

  17. 17.

    Kim, H. & Borkovich, K. A. A pheromone receptor gene, pre-1, is essential for mating type-specific directional growth and fusion of trichogynes and female fertility in Neurospora crassa. Mol. Microbiol. 52, 1781–1798 (2004).

    CAS  Article  Google Scholar 

  18. 18.

    Wang, Z., Kin, K., Lopez-Giraldez, F., Johannesson, H. & Townsend, J. P. Sex-specific gene expression during asexual development of Neurospora crassa. Fungal Genet. Biol. 49, 533–543 (2012).

    CAS  Article  Google Scholar 

  19. 19.

    Schmoll, M., Seibel, C., Tisch, D., Dorrer, M. & Kubicek, C. P. A novel class of peptide pheromone precursors in ascomycetous fungi. Mol. Microbiol. 77, 1483–1501 (2010).

    CAS  Article  Google Scholar 

  20. 20.

    Vitale, S. et al. Structure–activity relationship of α mating pheromone from the fungal pathogen Fusarium oxysporum. J. Biol. Chem. 292, 3591–3602 (2017).

    CAS  Article  Google Scholar 

  21. 21.

    Chitarra, G. S., Abee, T., Rombouts, F. M., Posthumus, M. A. & Dijksterhuis, J. Germination of Penicillium paneum conidia is regulated by 1-octen-3-ol, a volatile self-inhibitor. Appl. Environ. Microbiol. 70, 2823–2829 (2004).

    CAS  Article  Google Scholar 

  22. 22.

    Herrero-Garcia, E., Garzia, A., Cordobés, S., Espeso, E. A. & Ugalde, U. 8-Carbon oxylipins inhibit germination and growth, and stimulate aerial conidiation in Aspergillus nidulans. Fungal Biol. 115, 393–400 (2011).

    CAS  Article  Google Scholar 

  23. 23.

    Di Pietro, A. et al. Endopolygalacturonase PG1 in different formae speciales of Fusarium oxysporum. Appl. Environ. Microbiol. 64, 1967–1971 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Lopez-Berges, M. S., Rispail, N., Prados-Rosales, R. C. & Di Pietro, A. A nitrogen response pathway regulates virulence functions in Fusarium oxysporum via the protein kinase TOR and the bZIP protein MeaB. Plant Cell 22, 2459–2475 (2010).

    CAS  Article  Google Scholar 

  25. 25.

    Di Pietro, A. & Roncero, M. I. Purification and characterization of an exo-polygalacturonase from the tomato vascular wilt pathogen Fusarium oxysporum f.sp. lycopersici. FEMS Microbiol. Lett. 145, 295–299 (1996).

    CAS  Article  Google Scholar 

  26. 26.

    Puhalla, J. E. Compatibility reactions on solid medium and interstrain inhibition in Ustilago maydis. Genetics 60, 461–474 (1968).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. 27.

    Schindelin, J. et al. Fiji: an open-source platform for biological-image analysis. Nat. Methods 9, 676–682 (2012).

    CAS  Article  Google Scholar 

  28. 28.

    Sage, D. et al. DeconvolutionLab2: an open-source software for deconvolution microscopy. Methods 115, 28–41 (2017).

    CAS  Article  Google Scholar 

  29. 29.

    Sievers, F. et al. Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol. Syst. Biol. 7, 539 (2011).

    Article  Google Scholar 

  30. 30.

    Tamura, K. et al. MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol. Biol. Evol. 28, 2731–2739 (2011).

    CAS  Article  Google Scholar 

  31. 31.

    Tusnady, G. E. & Simon, I. The HMMTOP transmembrane topology prediction server. Bioinformatics 17, 849–850 (2001).

    CAS  Article  Google Scholar 

  32. 32.

    Spyropoulos, I. C., Liakopoulos, T. D., Bagos, P. G. & Hamodrakas, S. J. TMRPres2D: high quality visual representation of transmembrane protein models. Bioinformatics 20, 3258–3260 (2004).

    CAS  Article  Google Scholar 

  33. 33.

    Bailey, T. L. & Elkan, C. Fitting a mixture model by expectation maximization to discover motifs in biopolymers. Proc. Int. Conf. Intell. Syst. Mol. Biol. 2, 28–36 (1994).

    CAS  PubMed  Google Scholar 

Download references


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).

Author information




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.

Corresponding author

Correspondence to David Turrà.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

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).

Download citation

Further reading


Quick links

Sign up for the Nature Briefing newsletter for a daily update on COVID-19 science.
Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing