Fungal peptide pheromones are known as paracrine (inducing a response in nearby cells) sex signaling messengers. In the model yeast Saccharomyces cerevisiae, as in most ascomycete fungi, sexual development and mating between cells of the opposite sex are triggered by the interaction between two types of sex pheromones (named α and a) and their cognate receptors Ste2 and Ste3. This complex developmental process requires chemotropic growth between the two mating partners, followed by cell fusion and zygote formation. A single genomic locus named MAT defines mating-type identity by regulating the expression of only the correct pheromone/receptor pair, thereby avoiding inappropriate self-pheromone signaling. Thus, yeast MATa cells only express a-pheromone and the non-cognate Ste2 receptor, while MATα cells only express α-pheromone and Ste3.
In our work, we report a new and unexpected role of pheromone signaling in the ascomycete Fusarium oxysporum, a devasting soil-inhabiting plant pathogen which lacks a known sexual cycle. The story reaches back to 2015 when David Turrà, who at that time was a postdoc in the Di Pietro lab at University of Cordoba, Spain, discovered a chemotropic response to α-pheromone in a unisexual F. oxysporum strain of the α mating type (also called MAT1-1 in filamentous fungi). This finding was unexpected for two reasons. First, why should a fungus that lacks a sexual cycle respond to sex pheromone? Second, according to the yeast literature, mating type α cells should exclusively sense a-, but not α-pheromone, because they should not express the Ste2 receptor.
When I started working in the Di Pietro lab in 2015, I rapidly realized that F. oxysporum would provide a fantastic model to study new functions of fungal peptide pheromones beyond their canonical role in mating.
Indeed, in spite of its lack of a sexual cycle, a set of experiments rapidly suggested that F. oxysporum is actively using pheromone signaling:
1) α-type cells express both a- and α-pheromones and their receptors Ste3 and Ste2
2) These cells exhibit chemotropic growth towards either of the two F. oxysporum pheromones, which is mediated by cognate receptor signaling
3) A single α-type cell secretes and senses both types of pheromones via their cognate receptors and a conserved mitogen-activated protein kinase (MAPK) cascade
These findings suggested a novel and yet unrecognized role of self-pheromone sensing (also called autocrine signaling). We therefore asked whether asexual development of Fusarium is under the control of autocrine pheromone signaling. The finding that high cell density induces both pheromone and receptor expression suggested a link between population density and pheromone signaling. These results, in turn, drew our attention to one of the key developmental programs determined by population density: spore germination. Similar to many filamentous fungi, in F. oxysporum the germination of asexual spores (called conidia) is repressed at high cell densities. We noted that addition of synthetic α-pheromone can block germination even at normal spore densities, while genetic deletion of the α-pheromone or its receptor and downstream signaling components such as the MAPK module, can release the block in germination, even at inhibitory spore densities. Based on these results we proposed a model in which α-pheromone signaling acts to represses germination at high spore density, while a-pheromone signaling has the opposite effect by quenching α-pheromone-mediated inhibition. Because the peptide pheromones are widely conserved in ascomycete fungi, an intriguing question emerging from these findings is whether self- and non-self pheromone signaling have evolved at the same time or independently, and which of the two came first!