Insights into regulatory roles of MAPK-cascaded pathways in multiple stress responses and life cycles of insect and nematode mycopathogens.

Fungal entomopathogenicity may have evolved at least 200 million years later than carnivorism of nematophagous fungi on Earth. This mini-review focuses on the composition and regulatory roles of mitogen-activated protein kinase (MAPK) cascades, which act as stress-responsive signaling pathways. Unveiled by genomic comparison, three MAPK cascades of these mycopathogens consist of singular MAPKs (Fus3/Hog1/Slt2), MAPK kinases (Ste7/Pbs2/Mkk1), and MAPK kinase kinases (Ste11/Ssk2/Bck1). All cascaded components characterized in fungal entomopathogens play conserved and special roles in regulating multiple stress responses and phenotypes associated with biological control potential. Fus3-cascaded components are indispensable for fungal growth on oligotrophic substrata and virulence, and mediate cell tolerance to Na+/K+ toxicity, which is often misinterpreted as hyperosmotic effect but readily clarified by transcriptional changes of Na+/K+ ATPase genes and/or cell responses to osmotic polyols. Hog1-cascaded components regulate osmotolerance positively and phenylpyrrole-type fungicide resistance negatively, and also play differential roles in cell growth, conidiation, virulence, and responses to other stress cues. Ste11 has no stress-responsive role in the Beauveria Hog1 cascade despite an essential role in branched yeast Hog1 cascade. Slt2-cascaded components are required for mediation of cell wall integrity and repair of cell wall damage. A crosstalk between Hog1 and Slt2 cascades ensures fungal osmotolerance inside or outside insect. In nematode-trapping fungi, Slt2 is indispensable for cell wall integrity, conidiation, and mycelial trap formation, suggesting that the Slt2 cascade could have evolved along a distinct trajectory required for fungal carnivorism and dispersal/survival in nematode habitats. Altogether, the MAPK cascades are major parts of signaling network that regulate fungal adaptation to insects and nematodes and their habitats.