Bartonella taylorii; : A Model Organism for Studying; Bartonella; Infection; in vitro; and; in vivo

Bartonella; spp. are Gram-negative facultative intracellular pathogens that infect diverse mammals and cause a long-lasting intra-erythrocytic bacteremia in their natural host. These bacteria translocate; Bartonella; effector proteins (Beps) into host cells; via; their VirB/VirD4 type 4 secretion system (T4SS) in order to subvert host cellular functions, thereby leading to the downregulation of innate immune responses. Most studies on the functional analysis of the VirB/VirD4 T4SS and the Beps were performed with the major zoonotic pathogen; Bartonella henselae; for which efficient; in vitro; infection protocols have been established. However, its natural host, the cat, is unsuitable as an experimental infection model.; In vivo; studies were mostly confined to rodent models using rodent-specific; Bartonella; species, while the; in vitro; infection protocols devised for; B. henselae; are not transferable for those pathogens. The disparities of; in vitro; and; in vivo; studies in different species have hampered progress in our understanding of; Bartonella; pathogenesis. Here we describe the murine-specific strain; Bartonella taylorii; IBS296 as a new model organism facilitating the study of bacterial pathogenesis both; in vitro; in cell cultures and; in vivo; in laboratory mice. We implemented the split NanoLuc luciferase-based translocation assay to study BepD translocation through the VirB/VirD4 T4SS. We found increased effector-translocation into host cells if the bacteria were grown on tryptic soy agar (TSA) plates and experienced a temperature shift immediately before infection. The improved infectivity; in vitro; was correlating to an upregulation of the VirB/VirD4 T4SS. Using our adapted infection protocols, we showed BepD-dependent immunomodulatory phenotypes; in vitro; . In mice, the implemented growth conditions enabled infection by a massively reduced inoculum without having an impact on the course of the intra-erythrocytic bacteremia. The established model opens new avenues to study the role of the ...