BbCFEM7 contributes to the virulence of entomopathogenic fungi by competing for iron with Enterococcus mundtii

Common in fungal extracellular membrane (CFEM) domain proteins are a unique family of extracellular membrane proteins in fungi. Beauveria bassiana, as a entomopathogenic fungus, plays a critical role in the biological control of agricultural and forestry pests. However, the mechanism of interaction between entomopathogenic fungi and host gut microbes is rarely reported. The contribution of the BbCFEM7 gene to fungal growth virulence and immune defense was evaluated. According to the gut microbial diversity results, the absence of BbCFEM7 had a considerable influence on the insect gut bacterial communities, especially enterococcus. The infection with ΔBbCFEM7 strains significantly affected the contents of fatty acids (including short-chain fatty acids), organic acids, and indole metabolites in insect gut and hemolymph when compared to wild type strain (WT). Enterococcus mundtii was isolated in a fungus-infected insect hemolymph. According to in vitro and in vivo experiments, fungi and bacteria exerted an inhibitory effect on the growth of each other through rapid iron acquisition. Our study demonstrated that when B. bassiana infected insects, BbCFEM7 competed for iron ions with the E. mundtii escaping from the gut to the hemolymph, inducing metabolic dysregulation in the gut and hemolymph, thereby evading host immunity and augmenting fungal virulence. Enriching the host infection mechanism of fungal CFEM domain proteins, the results of this study provide a new reference for supplementing the Anna Karenina Principle (AKP) and further revealing the interaction between insect gut bacteria and pathogenic fungi.