Project description:Zoonotic pathogens account for the majority of emerging and re-emerging infectious diseases, yet the evolutionary mechanisms underlying their host specialization remain largely unexplained. Here, by combining comparative genomics and transcriptomics and the response of macrophages of varying hosts, we investigated the adaptive host evolution in the Bacterial celll zoonotic pathogen model Leptospira interrogans. Genomic analyses reveal that specialized genogroups exhibit specific signatures, characterized by reduced nucleotide diversity and restricted pangenome openness. We identify adaptive hotspots in genes encoding virulence factors, membrane proteins and environmental sensors, suggesting that positive selection in these genes is likely the primary drivers behing the emergence of genogroups. Focusing on the predominant genogroups associated with serogroups Icterohaemorrhagiae and Pomona, we uncover unique protein domain acquisitions linked to host adaptation, as well as a genogroup-specific gene expression programs potentially affecting virulence, secretion systems and metabolic pathways. Finally, infection of macrophages of different hosts elicits distinct immune responses, further validating ecological specialization of certain genogroups. Together, our findings suggest that intraspecies heterogeneity in L. interrogans is driven by niche specialization through differences in gene content, mutation rate variation and regulation of transcriptional programs.
