Microevolution of Bartonella grahamii driven by geographic and host factors.

Bartonella grahamii is one of the most prevalent Bartonella species in wild rodents and has been associated with human cases of neuroretinitis. The structure and distribution of genomic diversity in natural B. grahamii is largely unexplored. Here, we have applied a comprehensive population genomic and phylogenomic analysis to 172 strains of B. grahamii to unravel the genetic differences and influencing factors that shape its populations. The findings reveal a remarkable genomic diversity within the species, primarily in the form of single- nucleotide polymorphisms. The open pangenome of B. grahamii indicates a dynamic genomic evolution influenced by its ecological niche. Whole-genome data allowed us to decompose B. grahamii diversity into six phylogroups, each characterized by a unique "mosaic pattern" of hosts and biogeographic regions. This suggests a complex interplay between host specificity and biogeography. In addition, our study suggests a possible origin of European strains from Asian lineages, and host factors have a more significant impact on the genetic differentiation of B. grahamii than geographical factors. These insights contribute to understanding the evolutionary history of this pathogen and provide a foundation for future epidemiological research and public health strategies.

Importance: Bartonella grahamii has been reported worldwide and shown to infect humans. Up to now, an effective transmission route of B. grahamii to humans has not been confirmed. The genetic evolution of B. grahamii and the relationship between B. grahamii and its host need to be further studied. The factors driving the genetic diversity of B. grahamii are still controversial. The results showed that the European isolates shared a common ancestor with the Chinese isolates. Host factors were shown to play an important role in driving the genetic diversity of B. grahamii. When host factors were fixed, geographic barriers drove B. grahamii microevolution. Our study emphasizes the importance of characterizing isolate genomes derived from hosts and geographical locations and provides a new reference for the origin of B. grahamii.