Two NPC1 homologous proteins are involved in asexual reproduction, pathogenicity, and lipid trafficking in Phytophthora sojae.

Niemann-Pick type C (NPC) disease is characterized by lysosomal lipid storage disorders and defects in lipid trafficking, primarily due to mutations in the NPC1 protein. Two NPC1 homologous proteins are present in the genome of Phytophthora sojae, named as PsNPC1-1 and PsNPC1-2. Both proteins exhibit high sequence identity, consistent conserved functional domains, similar gene expression patterns, and comparable subcellular localization. Deletion of a single PsNPC1 gene did not result in significant phenotypic changes. However, simultaneous deletion of both PsNPC1 genes led to reduced mycelial growth, decreased sporangial production, impaired pathogenicity, and an inability to release normal zoospores in P. sojae. Furthermore, dysfunction of PsNPC1s did not completely block the absorption and utilization of exogenous sterols by P. sojae. While lipidome analysis revealed that the relative contents of fatty acyls, sphingolipids and saccharolipids were significantly elevated in the double-gene deletion mutant, alongside obvious alterations in glycerophospholipid and glycerolipid metabolism. Additionally, we observed a significant down-regulation of PsCDP-AP protein along with its interactions with both PsNPC1s. Deletion of PsCDP-AP also impaired asexual reproduction and virulence of P. sojae. These findings demonstrate that both PsNPC1 proteins may collaborate with other key regulators to modulate asexual reproduction, pathogenicity and lipid trafficking in P. sojae.