Genetic basis of Pseudonectria foliicola infection in humans and research on DKP-type natural products

Traditionally, Pseudonectria foliicola has been considered to have high host specificity, mainly infecting boxwood and causing typical leaf spot disease, with little threat to human health. However, in 2024, the first case of human keratitis caused by P. foliicola infection was reported in Zhejiang Provincial People’s Hospital, China. As a clinically rare pathogenic fungus, the pathogenic mechanism of P. foliicola remains unclear. This study analyzed the genetic basis of its human infection using genomics. We found at least 25 secondary metabolite biosynthetic gene clusters, including 417 virulence - related genes (nearly 50% related to human infections), and there is homology of virulence factors with known human pathogenic fungi. Fourteen compounds were isolated and identified, 7 of which contain diketopiperazine structures, predicted to have significant respiratory toxicity, neurotoxicity, etc. This study further fills the research gap in the cross - kingdom infection mechanism of this fungus. It provides new insights into the common rules of filamentous fungi breaking host barriers and is of great scientific significance and clinical reference value for preventing and controlling the new public health risks of plant - derived fungi transmitting to humans.