­­Tracking Rickettsia Conorii Subsp. Raoultii Infection in Vivo by Bioorthogonal Metabolic Labeling

Rickettsiae have increasingly emerged, posing a substantial public health threat in the world. It remains a challenge to study pathogenesis of the rickettsial pathogens due to difficulty in genetic manipulation of the obligate intracellular bacteria and limited available tools. Here we developed a bioorthogonal metabolic labeling technique without any requirement for genetic manipulation to understand pathogenesis of Rickettsia conorii subsp. raoultii, an emerging tick-borne pathogen. R. raoultii was efficiently labeled by azido sugars in Vero81 cells without interfering its infectivity. The fluorescent signals were visualized at injection sites, chest and abdomen areas until 14 days post infection, with azido-labeled R. raoultii in C3H/HeN mice, allowing us to noninvasively track infection and dissemination of R. raoultii through in vivo imaging. Importantly, the azido-labeled R. raoultii retained infectivity and pathogenicity comparable to its wild-type counterpart. Hence, bioorthogonal metabolic labeling provides a reliable and promising approach to tracking rickettsial infection in vivo for understanding pathogenesis.