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Intracellular bacterial pathogens divert multiple cellular pathways to establish their niche and persist inside their host. Coxiella burnetii, the causative agent of Q fever, secretes bacterial effector proteins via its Type 4 secretion system to generate a Coxiella-containing vacuole (CCV). Manipulation of lipid and protein trafficking by these effectors is essential for bacterial replication and virulence. Here, we have characterized the lipid composition of CCVs and found that the effector Vice interacts with phosphoinositides and membranes enriched in phosphatidylserine and lysobisphosphatidic acid. Remarkably, eukaryotic cells ectopically expressing Vice present compartments that resemble early CCVs in both morphology and composition. We found that the biogenesis of these compartments relies on the double function of Vice. The effector protein initially localizes at the plasma membrane of eukaryotic cells where it triggers the internalization of large vacuoles by macropinocytosis. Then, Vice stabilizes these compartments by perturbing the ESCRT machinery. Collectively, our results reveal that Vice is an essential C. burnetii effector protein capable of hijacking two major cellular pathways to shape the bacterial replicative niche. [ABSTRACT FROM AUTHOR]

Ezrin protein is involved in the interaction of actin cytoskeleton with membrane receptors such as CD44. It regulates plasma membrane dynamics and intracellular signaling. Coxiella burnetii, the etiologic agent of Q fever, is internalized into host cell through a poorly characterized molecular mechanism. Here we analyzed the role of ezrin and CD44 in the C. burnetii internalization by HeLa cells. The knockdown of ezrin and CD44 inhibited the bacterial uptake. Interestingly, at early stages of C. burnetii internalization, ezrin was recruited to the cell membrane fraction and phosphorylated. Moreover, the overexpression of non‐phosphorylatable and phosphomimetic ezrin mutants decreased and increased the bacterial entry, respectively. A decrease in the internalization of C. burnetii was observed by the overexpression of CD44 truncated forms containing the intracellular or the extracellular domains. Interestingly, the CD44 mutant was unable to interact with ERM proteins decreased the bacterial internalization. These findings demonstrate the participation of ezrin in the internalization process of C. burnetii in non‐phagocytic cells. Additionally, we present evidence that CD44 receptor would be involved in that process. [ABSTRACT FROM AUTHOR]

Intracellular bacterial pathogens establish their replicative niches within membrane-encompassed compartments, called vacuoles. A subset of these bacteria uses a nanochannel called the type 4 secretion system (T4SS) to inject effector proteins that subvert the host cell machinery and drive the biogenesis of these compartments. These bacteria have also developed sophisticated ways of altering the innate immune sensing and response of their host cells, which allow them to cause long-lasting infections and chronic diseases. This review covers the mechanisms employed by intravacuolar pathogens to escape innate immune sensing and how Type 4-secreted bacterial effectors manipulate host cell mechanisms to allow the persistence of bacteria. [ABSTRACT FROM AUTHOR]