E3 Ubiquitin Ligase Rsp5 Controls Lifestyle Transition and Pathogenicity in Arthrobotrys oligospora

Fungi have evolved sophisticated mechanisms to survive in complex environments. Nematode-trapping fungi (NTF) sense and recognize nematode prey to transition from a saprophytic to predatory lifestyle, rendering them promising biocontrol agents against plant-parasitic nematodes. Ubiquitination is essential for eukaryotic cellular homeostasis, yet its regulation of NTF development and pathogenicity remains unclear. Here, we identify the conserved E3 ubiquitin ligase AoRsp5 as a critical factor for all major life stages of Arthrobotrys oligospora. Knockout of rsp5 impairs Endosomal Sorting Complex Required for Transport (ESCRT)-mediated endocytosis and compromises plasma membrane integrity. These defects trigger disturbed cellular iron homeostasis and ferroptosis-like cell death, accompanied by global dysregulation of protein phosphorylation and ubiquitination as well as prominent suppression of MAPK cascades, which further attenuate virulence-associated signaling. Overall, our findings reveal a pivotal role for Rsp5-mediated ubiquitination in coordinating cellular homeostasis and developmental transitions in NTF.