Bridging historical antigenic profiling and whole-genome taxonomy in Rickettsia.

UNLABELLED: Historically, rickettsial diseases were classified primarily through antigenic profiling and serotyping, an approach that was later superseded by molecular taxonomy and phylogenetics. Recent advances in whole-genome sequencing (WGS) have revealed substantial taxonomic ambiguity within the genus Rickettsia, including nomenclatural redundancy and inconsistent species delineation, raising questions about the adequacy of current classification criteria for obligate intracellular bacteria. In parallel, long-standing serological data demonstrate extensive, structured antigenic relationships that have not been fully explored within modern genomic frameworks. In this review, we re-examine historical antigenic profiling in the context of contemporary WGS-based taxonomy and concordance between serological cross-reactivity and genetic relatedness across Rickettsia groups, particularly within and between the spotted fever, transitional, and typhus groups. Integrating antigenic and genomic data provides a polyphasic perspective that may aid in resolving current taxonomic uncertainty and has direct implications for serological diagnosis, antigen selection, and future taxonomic proposals. We argue that revisiting antigenic data alongside genomic metrics is essential to developing a coherent, biologically meaningful framework for Rickettsia classification. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at https://doi.org/10.1038/s44573-026-00004-2.