Comparative genomic and functional insights into life-cycle plasticity and host adaptation in a wild Nippostrongylus brasiliensis strain from Guangzhou

BACKGROUND: Nippostrongylus brasiliensis (rat hookworm) is a key model for studying human hookworm infection. RESULTS: A wild N. brasiliensis isolate from Guangzhou maintains high fecundity for 10 days and persists for 21 days in rats, which is twice as long as reported for reference strains, but survives only 10 to 11 days in mice while causing more severe pathology than that observed in rats. Comparative genomic, transcriptomic, and functional analyses were conducted to explore potential genetic factors associated with these phenotypic differences. Whole-genome sequencing revealed 92.6-93.3% identity to publicly available reference assemblies. Comparative analysis of strain-specific orthogroups identified astacin metalloproteases and four collagens, three being col-117-like genes, that were exclusively expressed in parasitic L4/L5 larvae. Two of these, col-117l12 and col-117l16, were up-regulated in mouse-derived worms compared to rat-derived worms. Lentivirus-mediated RNAi of col-117l16 reduced worm burdens by 77.2%, impaired reproduction, attenuated lesions, and disrupted adult cuticle structure and intestinal positioning. CONCLUSIONS: These findings highlight candidate genes potentially associated with N. brasiliensis life-cycle plasticity and host specificity; however, direct causal attribution of these phenotypic traits to specific genetic factors requires further validation under controlled experimental conditions.