Table 1.
Summary of secreted bacterial effector proteins that activate or inhibit caspase-3
| Bacterium | Effect on caspase-3? | Other caspases? | Mechanism of caspase-3 activation/inhibition | Bacterial effector responsible | Consequence | Reference |
|---|---|---|---|---|---|---|
| H. pylori | Activates | Cas-8 | Caspase-3 possibly activated directly | ND | Host cell killing | Ashktorab et al., 2002 |
| L. pneumophila | Activates | No | Caspase-3 activated directly | Dot/Icm effector | Prevents phagolysosome fusion | Molmeret et al., 2004; Zhu et al., 2013 |
| S. Dublin | Activates | ND | ADP ribosylating activity dependent | SpvB/SPI-2 TTSS | Important pathogenic mechanism | Browne et al., 2008 |
| No | ND but caspase-3 activated directly | PhoP regulation of spv locus | Survival during systemic infection | Valle and Guiney, 2005 | ||
| S. Typhimurium | Activates | No | Direct caspase-3 activation | SipA | Effector processing | Srikanth et al., 2010 |
| EPEC | Activates | ND | Cell cycle arrest activates caspase-3 | Cif | Delayed apoptosis favouring colonization | Samba-Louaka et al., 2009 |
| E. coli O157:H7 | Activates | Cas-9 | Mitochondrial disruption | N-terminal of EspF | Leads to attaching/effacing lesions | Zhao et al., 2013 |
| Y. pestis | Activates | Cas-8 | Death inducing signalling complex assembly | YopK/YopJ interplay | Alters inflammatory signalling | Peters et al., 2013 |
| V. vulnificus | Activates | No | Direct cleavage of caspase-3 | Metalloprotease vEP | Unknown, non-specific caspase-3 activation | Kim et al., 2007 |
| A. salmonicida/ | Activates | Cas-9 | Multiple mechanisms | AexT/AexU, Act2 and Hcp | Control of host inflammatory response | Rosenzweig and Chopra, 2013 |
| A. hydrophila | ||||||
| P. aeruginosa | Activates | Cas-8 | ADP-ribosylation, and possibly by caspase-3 binding | ExoS | Further dissemination | Kaufman et al., 2000 |
| F. tularensis | Activates | Cas-1 | Cytochrome-c release | Putative effectors IglC and IglI | Further dissemination | Santic et al., 2010 |
| S. Typhimurium | Inhibits | ND | Sustains Akt activation | SopB | Survival of intracellular replication niche | Knodler et al., 2005 |
| P. aeruginosa | Inhibits | ND | Stabilizes X-IAP | Secreted protein/possibly ExoA | Inhibiting apoptosis aids bacterial survival | Ashare et al., 2007 |
| F. tularensis | Inhibits | ND | NF-kB induction prevents apoptosis | T6SS effector, possibly IglC | Survival of infected cells/replication | Santic et al., 2010 |
| L. pneumophila | Inhibits | No | Dot/Icm dependent | Dot/Icm effector | Inhibition allows time for replication | Abu-Zant et al., 2007 |
| S. flexneri | Inhibits | ND | Anti-apoptosis expression/direct caspase binding | MxiE secretion and effector Spa15 | Protects intracellular replication niche | Clark and Maurelli, 2007; Faherty and Maurelli, 2009; Faherty et al., 2010 |
Activation of caspase-3 by individual effectors is indicated as well as whether this activation is potentially direct or through upstream initiator or other caspases. ND indicates that the mechanism of activation of caspase-3 or the involvement of other caspases was not defined in the study.