A plant fungus exposes lipid-transport defects linked to Niemann–Pick disease
A peer-reviewed study uses a cucumber-infecting fungus to investigate cellular lipid-transport functions associated with Niemann–Pick type C disease. Human NPC1 partly restored infection after loss of the corresponding fungal gene, while two compounds improved defects through different lipid pathways. The measurable fungal responses offer an experimental system rather than evidence of patient benefit.
Science··Midday
Two compounds restored fungal functions in different ways
Miglustat and a cyclodextrin compound improved defects in a plant-infecting fungus through different lipid pathways. The peer-reviewed study uses Colletotrichum orbiculare to investigate cellular functions associated with Niemann–Pick type C disease, in which NPC1 or NPC2 dysfunction disrupts lipid handling. Its experimental outcome is the fungus’s ability to enter cucumber tissue; recovery of this function does not establish a benefit for patients.[1]
Human NPC1 provided partial replacement
The fungus forms an appressorium, a specialised structure used to penetrate plant tissue. Losing NPC-related function disturbed lipid balance and actin organisation, impairing penetration. Introducing human NPC1 partly restored infection in a fungus lacking its own corresponding gene. Human NPC2 did not restore infection to a comparable extent. Disease-associated substitutions also differed: the fungal NPC2 change C121R showed severe loss, while the strong NPC1 defect involved I1039T alongside the additional E545G change.[1]
Sterol location separated the drug responses
With miglustat, sphingolipid-related defects and the infection outcome improved, while abnormal sterol location persisted. Sterol accumulation decreased with cyclodextrin, whose functional rescue followed a different time course. Imaging followed actin organisation at the penetration site alongside infection measurements. Some measurements counted at least 300 appressoria per biological replicate across three independent experiments. The model tests conserved cellular relationships, while the incomplete replacement by human genes limits direct transfer of individual variant effects.[1]
