The Biology, Ecology, and Pathogenesis of Borrelia burgdorferi Sensu Lato: Implications for Tick-Borne Disease and Prevention.

Borrelia burgdorferi is a highly evolved extracellular pathogen that employs diverse strategies to persist within a complex enzootic cycle. As the causative agent of Lyme disease (LD), it has been the focus of extensive research into host-pathogen interactions, particularly its mechanisms of survival in reservoir hosts and transmission dynamics, significantly advancing the field of tick-borne diseases. This review summarized the discovery and development of B. burgdorferi, and contributed towards a holistic view on the transmission dynamics and pathogenic mechanisms, with emphasis on the complement evasion mechanisms of B. burgdorferi, which informed the current prevention efforts. Looking forward, the application of single-cell high-throughput sequencing is expected to elucidate novel molecular mechanisms underlying the transmission, and artificial intelligence technology holds promise for developing global tick-borne disease databases and public communication platforms to support future prevention strategies. Overall, this review provides an integrated framework that bridges molecular pathogenesis, ecological dynamics, and technological innovation to inform both fundamental research and public health responses to LD.