Table 1.
The functions of SPI-1/2 effectors in S. Typhimurium, S. Typhi, and S. Paratyphi A.
| Effectors | Pathogenicity Island | Function (s) | Key Reference (s) |
|---|---|---|---|
| AvrA | SPI-1/SPI-2 | Stabilizes the intestinal epithelial permeability and tight junctions; cysteine protease; inhibits NF-κB signaling | [84] |
| GogA | SPI-2 | Cleaves the subset of NF-κB subunits; inhibits NF-κB signaling | [85,86] |
| GogB | SPI-2 | Inhibits NF-κB signaling | [85] |
| GtgA | SPI-2 | Inhibits NF-κB signaling | [85] |
| GtgE | SPI-1/SPI-2 | Promotes replication inside murine macrophages | [87] |
| PipA | SPI-2 | Cleaves the subset of NF-κB subunits; inhibits NF-κB signaling | [85] |
| PipB | SPI-2 | Targeted to SIFs | [88] |
| PipB2 | SPI-2 | Resists extraction by high salt, high pH; implicated in recruitment of kinesin-1 to SCV | [89] |
| SifA | SPI-2 | Detoxifies lysosomes; subverts human NLRP3 and NLRC4 inflammasome; required for SCV membrane stability; SIF formation; contributes to T3SS1-independent inflammation | [90] |
| SifB | SPI-2 | Targeted to SIFs | [82,83] |
| SipA | SPI-1 | Enhances actin filament assembly; promotes proliferation of cytosolic Salmonella; disrupts tight junctions; SCV trafficking | [91] |
| SipB | SPI-1 | Cholesterol-binding translocon component; triggers apoptosis via caspase-1 activation in macrophages and DCs | [82] |
| SipC | SPI-1 | Translocon component: mediates effector molecule translocation; promotes actin polymerization and bundling | [92] |
| SipD | SPI-1 | Translocon component | [93] |
| Slrp | SPI-1/SPI-2 | Inhibits the release of IL-1β | [87] |
| SopA | SPI-1 | A HECT-like E3 ubiquitin ligase | [94] |
| SopB | SPI-1 | Modulates SCV trafficking; phosphoinositide phosphatase; involved in phagosomal closure; enhances RhoG activation; disrupts tight junctions; stimulates chloride secretion; prevents apoptosis through activation of Akt | [95] |
| SopD | SPI-1/SPI-2 | SIF formation, prevents accumulation of Rab32 on SCV and SIFs | [87] |
| SopD2 | SPI-2 | Targeted to SIFs and late endosomes | [96] |
| SopE | SPI-1 | Promotes colonization of Salmonella; induces remodeling of actin | [97] |
| SopE2 | SPI-1 | Guanine nucleotide exchange factor for Cdc42; promotes pro-inflammatory signaling | [80] |
| SpiC | SPI-2 | Interferes with vesicular trafficking in host cells to prevent SCV-lysosome fusion | [92] |
| SptP | SPI-1 | Rho GAP domain functions in downregulating host membrane ruffling after entry; tyrosine phosphatase domain acts on ACK; vimentin; and presumably other substrates | [98] |
| SpvB | SPI-2 | Promotes macrophage apoptosis and P-body disassembly | [81,87] |
| SpvC | SPI-1/SPI-2 | Inhibits MAPK signaling | [99] |
| SpvD | SPI-1/SPI-2 | Inhibits NF-κB signaling | [87] |
| SrfJ | SPI-2 | Responses to intracellular conditions | [100] |
| SsaJ | SPI-2 | Prevents the phagocyte NADPH oxidase from trafficking toward SCVs | [101] |
| Ssav | SPI-2 | Prevents the phagocyte NADPH oxidase from trafficking toward SCVs | [102] |
| SseB | SPI-2 | Prevents the phagocyte NADPH oxidase from trafficking toward SCVs | [102] |
| SseF | SPI-2 | Tethers SCV to the Golgi network; contributes to Sif formation; replication of Salmonella in SCV | [87,103] |
| SseG | SPI-2 | Tethers SCV to the Golgi network; contributes to Sif formation; replication of Salmonella in SCV | [87,103] |
| SseJ | SPI-2 | Acyl transferase; cholesterol esterification; SCV membrane dynamics | [87,104] |
| SseK1 | SPI-2 | Inhibits TNFα-stimulated NF-κB signaling | [105] |
| SseK2 | SPI-2 | Related effectors that inhibits NF-κB signaling | [105] |
| SseL | SPI-2 | Inhibits autophagic clearance of cytosolic aggregates; induces late macrophage cell death; inhibits directional migration of macrophages and DCs | [106] |
| SspH2 | SPI-2 | An E3 ubiquitin ligase; activates NOD1 signaling | [79,87] |
| SsrA | SPI-2 | Prevents the phagocyte NADPH oxidase from trafficking toward SCVs | [102] |
| SteA | SPI-1/SPI-2 | SIF formation, vacuolar membrane partitioning | [107] |
| SteC | SPI-2 | Induces assembly of F-actin meshwork around SCV | [108] |
| SteD | SPI-2 | Inhibits antigen presentation and T cell activation | [17] |
NF-κB: Nuclear factor kappa beta; SCV: Salmonella-containing vacuole; NLRP3: the NOD-like receptor family, pyrin domain containing 3; NLRC4: NLR-family CARD-containing protein 4; SIF: Salmonella-induced filament; T3SS1: type III secretion system 1; HECT: homologous to E6-AP carboxy terminus; GAP: GTPase-activating phosphatase; ACK: a Cdc42-associated tyrosine kinase; NADPH: nicotinamide adenine dinucleotide phosphate; TNFα: tumour necrosis factor alpha; DCs: dendritic cells; NOD1: nucleotide-binding oligomerisation domain 1.