Coxiella burnetii: international pathogen of mystery

Abstract

Coxiella burnetii is an intracellular bacterium that causes acute and chronic Q fever. This unique pathogen has been historically challenging to study due to obstacles in genetically manipulating the organism and the inability of small animal models to fully mimic human Q fever. Here, we review the current state of C. burnetii research, highlighting new approaches that allow the mechanistic study of infection in disease relevant settings.

Keywords: Coxiella burnetii; Intracellular; Macrophage; Q fever.

Fig. 1.. Formation of the C. burnetii PV.

(Left) Schematic representation of the PV maturation pathway. C. burnetii SCV bind to the α_vβ₃ integrin receptor and are engulfed via phagocytosis by the macrophage, occupying a nascent phagosome from 0–6 h post-infection. Through autophagosome, endosome, and lysosome fusion, the early PV is formed within 6–24 h. Here, the SCV differentiates into the metabolically active LCV, allowing T4SS effector secretion. Through continuous fusion of autophagosomes, endosomes, and low pH lysosomes, the PV expands from 24 h onward, with an acidic pH ~ 5.0. In the late PV, the LCV transitions back to the SCV, maintaining both morphological forms of C. burnetii at late times post-infection. Lipid droplets also associate with the PV to regulate intracellular growth. (Right) Host proteins that associate with the PV at each point in the maturation stage.

Fig. 2.. C. burnetii targets alveolar macrophages in the human lung.

(A) Schematic representation of the alveolar environment and components present. SP-D = surfactant protein D. AS = alveolar space. (B) hPCLS were infected with mCherry-expressing C. burnetii (red) for 72 h, then processed for confocal immunofluorescence microscopy using CD206 antibody (green) to probe for alveolar macrophages and DAPI to stain nuclei (blue). Alveolar macrophages harbor expanded PV containing replicating C. burnetii while other cell types contain very few bacteria and no enlarged PV. (C) THP-1 cells (top) or hAMs (bottom) were infected with C. burnetii for 72 h, then processed for electron microscopy. N = nucleus. LD = lipid droplet. PV = parasitophorous vacuole. Bar, 20 μm. Both macrophage cell types support expanded PV development and robust bacterial growth.