Molecular Mechanisms and Metabolic Responses in the Biological Antagonism Between Trichoderma harzianum and Fusarium oxysporum

Trichoderma harzianum is an important biocontrol fungus widely used to manage vascular wilt caused by Fusarium oxysporum. However, the molecular regulation and metabolic responses underlying different confrontation modes remain unclear. In this study, we integrated non-targeted and targeted metabolomics, transcriptomics, mycotoxin detoxification assays, and RNA interference (RNAi) to systematically investigate antagonistic mechanisms under direct and indirect confrontation conditions. Direct confrontation strongly inhibited F. oxysporum via physical mycoparasitism and was accompanied by enhanced mycotoxin biosynthesis. In contrast, indirect confrontation induced metabolic reprogramming, characterized by increased amino acid and energy metabolism, and promoted biomass accumulation in T. harzianum. Targeted metabolomics identified 38 core mycotoxins, several of which were significantly enriched during direct confrontation. Detoxification assays further showed that T. harzianum reduced multiple mycotoxins in a concentration-dependent manner, likely through a combination of physical adsorption and potential biochemical transformation, although the exact mechanisms remain unclear. Transcriptomic analysis revealed extensive differential gene expression in both fungi, particularly in pathways related to redox homeostasis and metabolic regulation. In addition, exogenous dsRNA effectively reduced the expression of selected pathogenicity-related genes in F. oxysporum at the transcriptional level. Overall, these findings highlight mode-specific antagonistic responses and provide a descriptive framework for understanding fungal interactions. The potential integration of microbial biocontrol with RNAi-based approaches is discussed as a conceptual perspective that requires further experimental validation.