Bioluminescent imaging to investigate Coxiella burnetii pathogenesis identifies adipose tissue as a host niche for infection

Coxiella burnetii is a gram-negative, obligate intracellular pathogen that causes Q fever in humans. In vivo research on C. burnetii is limited due to the classification of the Nine Mile phase I (NMI) strain as a select agent that requires biosafety level 3 containment. The isogenic Nine Mile phase II (NMII) strain can be cultured safely at biosafety level 2 and has been shown to infect immunocompromised mice, which suggests this strain could be used to investigate virulence phenotypes in vivo. This study developed a bioluminescent imaging (BLI) model using NMII to non-invasively monitor C. burnetii infections in mice. Here, we show that BLI enables tracking of bacteria in an animal host, identification of bacterial virulence differences, and investigation of host determinants of immunity. Using BLI, we show that NMII resides primarily in visceral adipose tissue following intraperitoneal infection of mice. Intracellular replication of C. burnetii in adipocytes was confirmed using cultured cells ex vivo. These data indicate that adipose tissue can serve as a niche for C. burnetii replication. This study underscores the utility of BLI in advancing C. burnetii research and highlights the need for further exploration into the role of adipocytes in the disease Q fever and bacterial persistence in vivo.