Biocontrol Potential of Entomopathogenic Fungi Against Plant-Parasitic Nematodes: A <i>Caenorhabditis elegans</i>-Based Screening and Mechanistic Study

Plant-parasitic nematodes and insect pests critically threaten agricultural productivity, but chemical pesticides face limitations due to resistance and environmental concerns, necessitating eco-friendly biopesticides targeting both pests and nematodes. Here, we developed a high-throughput screening platform using <i>Caenorhabditis elegans</i> to identify entomopathogenic fungi exhibiting nematocidal activity against <i>Meloidogyne incognita</i>. Among 32 tested strains, nine <i>Metarhizium</i> spp. and one <i>Beauveria</i> strain demonstrated dual efficacy against <i>C. elegans</i> and <i>M. incognita</i>. <i>Metarhizium anisopliae</i> CQMa421 showed the highest virulence, suppressing nematode reproduction by 42.7% and inducing >80% mortality. Pot experiments revealed a 50% reduction in the root galling index and 50.3% fewer root galls in <i>Solanum lycopersicum</i>. The CQMa421 filtrate caused irreversible locomotor deficits and reduced egg hatching rates by 28%. Concurrently, intestinal damage, elevated oxidative stress and autophagy were observed in <i>C. elegans</i>. This was accompanied by a transcriptome-wide modulation of genes involved in detoxification and immune defense pathways. These findings demonstrate the efficacy of our <i>C. elegans</i>-based screening method for identifying fungi with nematocidal potential. CQMa421’s virulence against <i>M. incognita</i> suggests its promise for pest management, while molecular insights highlight pathways that may contribute to the future design of future nematicides. This study advances fungal biocontrol agents and offers a sustainable strategy for agriculture.