Unveiling a Novel Role of Cdc42 in Pyruvate Metabolism Pathway to Mediate Insecticidal Activity of Beauveria bassiana

The small GTPase Cdc42 acts as a molecular switch essential for cell cycles and polar growth in model yeast, but has not been explored in Beaurveria bassiana, an insect-pathogenic fungus serving as a main source of fungal formulations against arthropod pests. Here, we show the indispensability of Cdc42 for fungal insecticidal activity. Deletion of cdc42 in B. bassiana resulted in a great loss of virulence to Galleria mellonella, a model insect, via normal cuticle infection as well as defects in conidial germination, radial growth, aerial conidiation, and conidial tolerance to heat and UVB irradiation. The deleted mutant’s hyphae formed fewer or more septa and produced unicellular blastospores with disturbed cell cycles under submerged-culture conditions. Transcriptomic analysis revealed differential expression of 746 genes and dysregulation of pyruvate metabolism and related pathways, which were validated by marked changes in intracellular pyruvate content, ATP content, related enzyme activities, and in extracellular beauvericin content and Pr1 protease activity vital for fungal virulence. These findings uncover a novel role for Cdc42 in the pathways of pyruvate metabolism and the pyruvate-involved tricarboxylic acid cycle (TCA cycle) and a linkage of the novel role with its indispensability for the biological control potential of B. bassiana against arthropod pests.