Figure 2.

Intracellular trafficking route of Coxiella and Legionella. (A) Coxiella initially resides in a parasitophorous vacuole (PV) that takes hours to days to mature into a compartment resembling a lysosome. Rab5 and Rab7 have been shown to be sequentially present on the PV, with Rab5 showing maximal recruitment approximately 20 min p.i. before being replaced by Rab7 which remains on the PV throughout the infection. Between 6 and 12 h post- infection, the PV acquires autophagy markers including LC3 and Rab24. Then, p62 colocalizes with LC3 on PV membranes containing ubiquitinated proteins without affecting the bacterial replication. In addition, Rab1b labels the PV membrane at later p.i. times (6 h). (B) Legionella actively evades endocytic trafficking and creates an ER-derived niche. Effector proteins such as DrrA/SidM, LidA, and RalF, secreted by the T4SS, prolong the association with the ER and inhibit the immediate delivery to lysosomes. Likewise, RavZ cleaves the membrane-conjugated LC3 from pre-autophagosomal structures to persist in immature autophagosomal vacuoles for a period of time that is suitable to differentiate into an acid-resistant replicative form. Then, the subsequent secretion of the effector LepB releases the block to autophagosome maturation, and the adapted progeny continues to replicate within autophagolysosomes.