Ribosome and respiration defects drive developmental arrest of Schistosoma japonicum in non-permissive hosts

Parasitic flatworms of the genus Schistosoma infect a wide range of definitive hosts, which differ in their ability to support parasite development. Unlike in permissive host mice, Schistosoma japonicum undergoes pronounced developmental arrest in non-permissive hosts like rats; however, the molecular basis underlying host-dependent developmental outcomes remains unclear. Here, we combine morphological analyses, bulk and single-cell RNA sequencing to map the developmental trajectories of S. japonicum in permissive (mouse) and non-permissive (rat) hosts. We identify a critical divergence between 12 and 24 days post-infection, during which parasites in rats exhibit dysregulated ribosome biogenesis and impaired anaerobic glycolysis. In vitro and in vivo functional studies further demonstrate that these disruptions trigger cell cycle arrest and energy deficiency, ultimately leading to developmental arrest. Our study presents a high-resolution single-cell atlas of S. japonicum across host environments and highlights parasite-intrinsic translational and metabolic pathways as key determinants of host permissiveness. These findings provide a parasite-centered insight into host permissiveness and offer potential avenues for targeting schistosome development and transmission. Morphological, transcriptomic and functional analyses compare Schistosoma japonicum development in nonpermissive rats and permissive mice. Ribosomal and glycolytic defects impair cell cycle and energy metabolism, causing developmental arrest.