Effector Protein Cig2 Decreases Host Tolerance of Infection by Directing Constitutive Fusion of Autophagosomes with the Coxiella-Containing Vacuole.

Coxiella burnetii is an obligate, intracellular bacterial pathogen that replicates inside a unique, lysosome-like compartment called the Coxiella-containing vacuole (CCV). Over 130 bacterial effector proteins are delivered into the host cell cytosol by the C. burnetii Dot/Icm type IV secretion system. Although the Dot/Icm system is essential for pathogenesis, the functions of most effectors remain unknown. Here we show that the effector protein Cig2 is essential for converting the CCV to an organelle that is similar to the autolysosome. Cig2 function promotes constitutive fusion between the CCV and autophagosomes generated by selective autophagy. Cig2-directed biogenesis of an autolysosomal vacuole is essential for the unique fusogenic properties of the CCV and for virulence in an animal model of disease. This work highlights how bacterial subversion of the host autophagy pathway can influence the cell biological properties of the CCV and influence the host response to infection.