Table 2.
Strategies used by the effectors from T4SS, T6SS, and T7SS to manipulate autophagy.
| Bacteria | Effectors | Host model | Description | Bacterial survival | References |
|---|---|---|---|---|---|
| Interfering with signaling or proteins involved in autophagy | |||||
| Legionella pneumophila | RavZ (T4SS) | HEK293 cells and MCF-7 cells | Cleaving LC3 off the membrane and modifying LC3 by its de-conjugating enzyme activity | Not applicable | (34, 35) |
| Anaplasma phagocytophilum | Ats-1 (T4SS) | THP-1 cells, RF/6A cells and Beclin-1+/− mice | Binds host Beclin-1 protein and hijacks Beclin-1-Atg14L autophagy initiation | Not applicable | (36) |
| Vibrio parahaemolyticus | VgrG2 (T6SS) | RAW264.7 cells | Possibly reduces the level of intracellular cAMP | Not applicable | (37) |
| Ehrlichia chaffeensis | Etf-1 (T4SS) | THP-1 cells, HEK293 cells and DH82 cells | Targets host RAB5, Beclin-1, VPS34, and autophagy - initiating PtdIns3K to ehrlichial inclusions to induce autophagy | Ehrlichia chaffeensis proliferation requires class III PtdIns3K activation and BECN1, and is enhanced by induction of autophagy with rapamycin | (6) |
| Preventing recognition by autophagy mechanisms | |||||
| Bartonella quintana | BepE (T4SS) | HeLa cells, HEK293 cells and HUVECs | Induces selective autophagy by conjugation with K63 poly-ubiquitin chain | Not applicable (But cells with BepE-induced autophagy are about 3-fold more effective at engulfing Bartonella quintana than cells with BepE-induced filopodia and membrane ruffles) | (38) |
| Subverting autophagic components for bacterial survival | |||||
| Legionella pneumophila | DrrA, LidA, RalF and LepB (T4SS) | Primary mouse macrophages | Interacts with RAB proteins to manipulate autophagosomal maturation | Not applicable | (39) |
| Coxiella burnetii | Cig2 (T4SS) | HeLa cells | Promotes the fusion of Coxiella-containing vacuoles with autophagosomes to maintain this vacuole in an autolysosomal stage of maturation | Coxiella burnetii is highly resistant to environmental stresses and is able to replicate in acidified lysosome-derived vacuoles | (40) |
| Mycobacterium tuberculosis (Note: this strain is not suitable for using Gram stain) | ESAT-6 (T7SS) | Human primary DCs | Impairs autophagosome-lysosome fusion | Not applicable | (41) |
| Mediating autophagy by subverting host cell homeostasis | |||||
| Legionella pneumophila | LpSpl (T4SS) | HEK-293T cells and THP-1 macrophages | Inhibits autophagy by disrupting host sphingolipid biosynthesis | Not applicable | (42) |
| Pseudomonas aeruginosa | TplE (T6SS) | HeLa cells and HEK293T cells | Activates autophagy responses by subverting ER homeostasis | In intra- and inter-species competition studies show that the loss of tplE gave rise to a growth advantage of the recipient strain | (43) |
| Manipulating autophagy via unknown mechanisms | |||||
| Brucella | VceA (T4SS) | HPT-8 cells | Suppresses autophagy via unknown mechanisms | Not applicable | (44) |
| Escaping LC3-associated phagocytosis | |||||
| Legionella species | RavZ (T4SS) | HEK293 cells and MCF-7 cells | Cleaving LC3 off the membrane and modifying LC3 by its de-conjugating enzyme activity | Not applicable | (34, 45) |
| Legionella pneumophila | LpSpl (T4SS) | May be responsible for inhibiting LAP | Not applicable | (42, 46) | |