Thiolutin Is a Potential Fungicide for Controlling <i>Phytophthora nicotianae</i> and Its Mechanistic Study

<i>Phytophthora nicotianae</i> is a destructive plant pathogen that causes significant agricultural losses, with current chemical control strategies leading to resistance and environmental concerns. This study identified thiolutin, a dithiopyrrolone antibiotic from <i>Streptomyces luteireticuli</i> ASG80, as a potent antifungal agent against multiple <i>Phytophthora</i> species. Thiolutin exhibited strong in vitro activity, with an EC₅₀ value of 0.8266 μg/mL, significantly reduced disease incidence and <i>Phytophthora</i> abundance in vivo, outperforming conventional fungicides such as metalaxyl. Transcriptomic analysis revealed significant downregulation of key genes in energy metabolism pathways, including mitochondrial function and oxidative phosphorylation, indicating impaired energy production and cellular metabolism. Microscopic and biochemical analyses further demonstrated that thiolutin disrupts cell membrane integrity, induces reactive oxygen species accumulation, and damages mitochondria, ultimately leading to energy metabolism disruption and fungal programmed cell death. These findings highlight thiolutin's potential as an environmentally friendly alternative for managing <i>Phytophthora</i>-induced plant diseases.