Culture Degeneration Reduces Sex-Related Gene Expression, Alters Metabolite Production and Reduces Insect Pathogenic Response in Cordyceps militaris

Abstract

Cordyceps militaris is an entomopathogenic ascomycete, known primarily for infecting lepidopteran larval (caterpillars) and pupal hosts. Cordycepin, a secondary metabolite produced by this fungus has anti-inflammatory properties and other pharmacological activities. However, little is known about the biological role of this adenosine derivate and its stabilising compound pentostatin in the context of insect infection the life cycle of C. militaris. During repeated subcultivation under laboratory conditions a degeneration of C. militaris marked by decreasing levels of cordycepin production can occur. Here, using degenerated and parental control strains of an isolate of C. militaris, we found that lower cordycepin production coincides with the decline in the production of various other metabolites as well as the reduced expression of genes related to sexual development. Additionally, infection of Galleria mellonella (greater wax moth) caterpillars indicated that cordycepin inhibits the immune response in host haemocytes. Accordingly, the pathogenic response to the degenerated strain was reduced. These data indicate that there are simultaneous changes in sexual reproduction, secondary metabolite production, insect immunity and infection by C. militaris. This study may have implications for biological control of insect crop pests by fungi.

Effects of MAT1-2 Spore Ratios on Fruiting Body Formation and Degeneration in the Heterothallic Fungus Cordyceps militaris

“…However, a highly excessive number of MAT1-2 spores can cause degeneration (Figure 3). A recent comparative analysis with quantitative real-time PCR also indicated that the expression of the MAT1-2-1 gene in a degenerated C. militaris strain was significantly higher than in its parental strain [28]. Based on this information and our results, we suggest that the abundance of the MAT1-1 monokaryotic spores in the mating combinations can support the stability of the fruiting body formation in the heterokaryotic C. militaris strains.…”

Molecular Mechanisms Underlying Phenotypic Degeneration inCordyceps militaris: Insights from Transcriptome Reanalysis and Osmotic Stress Studies

“…We compared their radical expansion after 12 days of culture on PDA plates and found that the degenerate strain reduced radical expansion by approximately 50% compared to the wild type strain. While Wellhan et al (2021) reported nonsignificantly slower radical growth rates in the degenerate strain, they did not show its ability to form fruiting bodies, so it is unclear whether the “degenerate” strain is truly degenerate (25). Our study revealed that the degenerated strain showed a significantly higher conidia density than the wild-type strain, which contradicts the findings of Meiyu et al (2022).…”

The phenomenon of strain degeneration in biotechnologically relevant fungi

“…Cordyceps militaris, for example, is commercially cultivated as a pharmaceutical and food resource and frequently degenerates through subculture and storage. Next to the degeneration of fruiting body formation, secondary metabolite production is reduced, leading to high economic losses (Xiong et al 2013;Sun et al 2017;Yin et al 2017;Lou et al 2019;Wellham et al 2021). Their ability to sexually reproduce adds another layer of complexity, which might be the reason why this is not reviewed in the literature.…”