Rickettsia japonica strain YC21 from a fatal human case in China: comparative genomics and experimental characterization of infection phenotypes

Rickettsia japonica causes Japanese spotted fever (JSF), an emerging severe tick-borne disease in East Asia. We recently isolated strain YC21 from the first laboratory-confirmed fatal JSF case in China. This study aimed to characterize the genomic features and infection phenotype of this single clinically derived isolate, rather than to establish its relative virulence. Phylogenetically, YC21 clustered within Clade III, which contains all Chinese isolates and one Japanese strain. Clades II and III share a conserved 15-bp deletion in the adhesin gene rOmpB/Sca5 . The YC21 genome harbored variations, including two YC21-specific SNPs identified within the analyzed dataset and alterations in surface antigen genes. In vitro, under standardized Vero cell assay conditions, YC21 showed a higher qPCR-derived rickettsial DNA burden than the selected SFG reference strains. In vivo, YC21 infection induced clinical illness, qPCR-derived rickettsial DNA burden in multiple tissues, and liver and lung lesions in C3H/HeN mice. This study provides a genomic and experimental characterization of a single Chinese R. japonica isolate from a fatal human case. The genomic variations identified here should be regarded as candidate features requiring functional validation. Further comparative studies using additional R. japonica strains are needed to determine whether these features contribute to strain-level differences in infection phenotype or disease severity.