Effects of Cordycepin in <i>Cordyceps militaris</i> during Its Infection to Silkworm Larvae

Cordyceps militaris produces cordycepin, a secondary metabolite that exhibits numerous bioactive properties. However, cordycepin pharmacology in vivo is not yet understood. In this study, the roles of cordycepin in C. militaris during its infection were investigated. After the injection of conidia, C. militaris NBRC100741 killed silkworm larvae more rapidly than NBRC103752. At 96 and 120 h, Cmcns genes (Cmcns1-4), which are part of the cordycepin biosynthesis gene cluster, were expressed in fat bodies and cuticles. Thus, cordycepin may be produced in the infection of silkworm larvae. Further, cordycepin enhanced pathogenicity toward silkworm larvae of Metarhizium anisopliae and Beauveria bassiana, that are also entomopathogenic fungi and do not produce cordycepin. In addition, by RNA-seq analysis, the increased expression of the gene encoding a lipoprotein 30K-8 (Bmlp20, KWMTBOMO11934) and decreased expression of genes encoding cuticular proteins (KWMTBOMO13140, KWMTBOMO13167) and a serine protease inhibitor (serpin29, KWMTBOMO08927) were observed when cordycepin was injected into silkworm larvae. This result suggests that cordycepin may aid the in vivo growth of C. militaris in silkworm larvae by the influence of the expression of some genes in silkworm larvae.