Table 1.
Proteins that have been delivered by the bacterial T3SSs.
| Target protein | Host cell | Delivery strain | T3SS effector fusion | Application | Ref. | |
|---|---|---|---|---|---|---|
| Antigen or epitope | Pathogens' antigen | |||||
| Influenza virus nucleoprotein (IVNP) | Antigen-presenting cells (APCs) | Salmonella enterica serovar Typhimurium (ΔaroA/sptP) | SptP-IVNP366–374 | Antiviral vaccine | Rüssmann et al., 1998 | |
| p60 antigen of Listeria monocytogenes | APCs | Yersinia enterocolitica (wild-type) | YopE1–138-p60 | Anti-bacterial vaccine | Rüssmann et al., 2000 | |
| Listeriolysin O and p60 of L. monocytogenes | APCs | S. typhimurium (ΔaroA/sptP) |
YopE1–138-listeriolysin O; YopE1–138-p60 |
Anti-bacterial vaccine | Rüssmann et al., 2001 | |
| Listeriolysin O of L. monocytogenes | Dendritic cells (DCs) | Y. enterocolitica (pYV) | YopE1–138-listeriolysin O 51–363 | Vaccination of mice against Listeria infection | Trülzsch et al., 2005 | |
| Gag proteins of simian and human immunodeficiency viruses (SIV and HIV) | APCs | S. typhimurium (ΔphoP/phoQ) |
SopE1–104-SIV-Gag4–284; SopE1–104-HIV-GagΔ392–426 |
Antiviral vaccine | Chen et al., 2006 | |
| p60 of L. monocytogenes Tumor-associated antigen (TAA) or model protein | Macrophages | S. typhimurium (ΔaroA/sptP) | SspH2-p60130–484 | Anti-bacterial vaccine | Panthel et al., 2008 | |
| MAGE | DCs | Y. enterocolitica (ΔyopHOPEM) | YopE1–130-MAGE-A1 | Stimulate specific cytolytic T lymphocytes (CTL) | Duffour, 1999 | |
| p60 from L. monocytogenes | APCs | S. typhimurium (ΔaroA/sptP) | YopE1–138-p60217–225 | Anti-tumor immunotherapy (fibrosarcoma) | Panthel et al., 2006 | |
| NY-ESO-1 | APCs | S. typhimurium (ΔphoP/phoQ) | SopE1–100-NY-ESO-1 | Anti-tumor immunotherapy (sarcoma) | Nishikawa et al., 2006 | |
| Ovalbumin (Ova) | DCs | Pseudomonas aeruginosa (ΔexoS/exoT) | ExoS1–54-Ova | Anti-tumor immunotherapy | Epaulard et al., 2006 | |
| Hepatitis B virus x (HBx) | Macrophages | S. typhimurium (ΔaroA) | SspH2-HBx | Anti-tumor immunotherapy (hepatocellular carcinoma) | Wang et al., 2008 | |
| Survivin | APCs, macrophages | S. typhimurium (ΔpurD/htrA) | SseF-Survivin | Anti-tumor immunotherapy (colon carcinoma and glioblastoma) | Xiong et al., 2010 | |
| Tyrosinase-related protein 2 (TRP2) | APCs | S. typhimurium (ΔaroA) | SopE1–100-Hsp70-TRP2153–417 | Anti-tumor immunotherapy (melanoma) | Zhu et al., 2010 | |
| TRP2 | APCs | P. aeruginosa (ΔexoS/exoT) | ExoS1–54-TRP2L125–376 | Anti-tumor immunotherapy (glioma tumor) | Derouazi et al., 2010 | |
| Pan-HLA-DR-binding epitope (PADRE); TRP2; GP100 | APCs | P. aeruginosa (ΔexoS/exoT/aroA/lasI) |
ExoS1–54-PADRE-TRP2L125–376 ExoS1–54-PADRE-GP10021–150 |
Anti-tumor immunotherapy | Wang et al., 2012 | |
| Vascular endothelial growth factor receptor 2 (VEGFR2) | APCs | S. typhimurium (ΔaroA/sptP) | YopE1–138-VEGFR2352–411 | Anti-tumor immunotherapy (melanoma) | Jellbauer, 2012 | |
| Ovalbumin (Ova) | APCs | P. aeruginosa (ΔexoS/exoT/uvrA/uvrB) | ExoS1–54-Ova | Anti-tumor immunotherapy (melanoma) | Le Gouëllec et al., 2013;Chauchet et al., 2016 | |
| Antibody | Heavy-chain antibodies (Nanobody or VHH) recognizing amylase (Vamy) and GFP (Vgfp) Nanobody recognizing EGFP (VHHGFP4) | HeLa cells | Enteropathogenic E. coli (EPEC) (Δeae/tir/map/espF) | EspF1–20-Vamy EspF1–20-Vgfp | Target specific intracellular proteins | Blancotoribio et al., 2010 |
| Nanobody recognizing EGFP (VHHGFP4) | HeLa cells | Y. enterocolitica (ΔyopHOPEMT/asd) | YopE1–138-VHHGFP4 | Nanobody-dependent subcellular localization | Ittig et al., 2015 | |
| Enzyme | Cytosolic enzymes | |||||
| Adenylate cyclase (Cya) | HeLa cells | Y. enterocolitica (wild-type) | YopE1–130-Cya | Study the translocation mechanism | Sory and Cornelis, 1994 | |
| Dihydrofolate reductase (DHFR) | – | Y. enterocolitica (ΔyopHOPEMT) | YopE1–52-DHFR | Study the type III secretion mechanism | Feldman et al., 2002 | |
| Glycogen synthase kinase (GSK) | HeLa cells | Yersinia pestis (ΔyopE) | YopE1–129-GSK | Study the translocation of T3S and T4S substrates | Garcia et al., 2006 | |
| Nucleases | ||||||
| Cre recombinase | TE26 cells; mouse ESCs and iPSCs | P. aeruginosa (ΔexoSTY) | ExoS1–54-NLS-Cre (Fig. 3) | Gene editing | Bichsel et al., 2011 | |
| TALEN | HeLa cells; mouse ESCs; human ESCSs and iPSCs | P. aeruginosa (ΔexoSTY/ndk/xcpQ/lasI/rhlI/popN) | ExoS1–54-NLS-TALEN (Fig. 3) | Gene editing | Jia et al., 2014; Jia et al., 2015 | |
| Transcription factor | MyoD | Mouse embryonic fibroblasts (MEF) | P. aeruginosa (ΔexoSTY) | ExoS1–54-MyoD (Fig. 3) | Muscle cell reprogramming | Bichsel et al., 2013 |
| Gata4, Mef2c and Tbx5 | Mouse ESCs | P. aeruginosa (ΔexoSTY/ndk/xcpQ/lasI/rhlI/popN) | ExoS1–54-Gata4 (Fig. 3) ExoS1–54-Mef2c (Fig. 3) ExoS1–54-Tbx5 (Fig. 3) | Cardiomyocytes diffferentiation | Bai et al., 2015 | |
| Oct4, Sox2 and Nanog | human fibroblasts and hematopoietic human stem cells | P. aeruginosa (ΔexoST) | ExoS1–54-Oct4 | Induction of the pluripotency; cell reprogramming | Berthoin et al., 2016 | |
| Fluorescent protein | GFP | HEp-2 cells | Y. enterocolitica (wild-type) | YopE1–138–GFP | Study of protein translocation via T3SS | Jacobi et al., 1998 |
| The 11th strand of the GFP β-barrel (GFP11) | HeLa cells | S. typhimurium (ΔpipB2) | PipB2-GFP11; SteA-GFP11 | Tracking intracellular localization of effectors | Van Engelenburg and Palmer, 2010 | |
| EGFP and mCherry | HeLa cells | Y. enterocolitica (ΔyopHOPEMT/asd) | YopE1–138-EGFP; YopE1–138-EGFP-NLS; YopE1–138-mCherry; YopE1–138-NLS-mCherry | Tracking intracellular localization of translocated proteins | Ittig et al., 2015 | |
| Others | Neutrophil cytosolic factor p67-phox | p67phox-deficient lymphocytes | P. aeruginosa (wild-type) | ExoS1–129-p67phox | Cellular therapy | Polack, 2000 |
| Anti-inflammatory cytokines IL-10 and IL-1 receptor antagonist (IL-1ra) | Lung tissue | Shigella flexneri (wild-type) | YopE1–50-IL-10; IpaH1–60-IL-10; IpaH1–60-IL-1ra | Immunomodulation | Chamekh, 2008 | |
| Bacterial T3SS effectors | HeLa cells | Y. enterocolitica (ΔyopHOPEMT) | YopE1–138-IpgB1 YopE1–138-IpgB2 YopE1–138-Map | Study the cell biological effects of bacterial effectors | Wölke et al., 2011 | |
| Pro-apoptotic protein: BH3 interacting-domain death agonist (BID) and truncated BID (tBID) | HeLa cells | Y. enterocolitica (ΔyopHOPEMT/asd) | YopE1–138-BID YopE1–138-tBID | Study of mechanism of apoptosis/intracellular signal transduction | Ittig et al., 2015 | |