Ecological specialization and constrained evolution shape virulence diversity in zoonotic pathogen L. interrogans

Leptospira interrogans circulates among an exceptionally broad range of reservoirs, but only serogroup Icterohaemorrhagiae dominates the global burden of human leptospirosis, raising fundamental questions about its ecological and pathogenic success. Here, we integrate a global genomic dataset to dissect host adaptation in L. interrogans.

Population genomic analyses reveal that serogroups Icterohaemorrhagiae and Pomona dominate worldwide and display signatures of ecological specialization. These serogroups have followed distinct evolutionary trajectories that are central to host specialization, characterized by extensive divergence in membrane and signaling genes, together with the acquisition of specialized functional repertoires linked to host adaptation.