HeLa cells - for 0,5 h incubated with the protein EPEC NleC and stimulated with IL1b
© A. S. Stolle
HeLa, YopH / Rab7 Co-Staining (6h) | HeLa, YopH / CD63 Co-Staining (24h)
© B. Grabowski

    Autopenetration of bacterial effector proteins and modulation of signalling responses in cellular barriers

    Effector proteins can also enter host cells in a type III secretion system (T3SS)-independent manner thereby widening their potential functional range to modulate cellular barriers. In this regard, we identified the entire group of bacterial leucine-rich repeat (LPX) effector proteins as so far unknown cell-penetrating effector proteins (CPE), which provided further evidence for a general concept of T3SS-independent translocation. Now we will elucidate the effects of this novel class of CPE in modulating immune responses in cell-culture and animal models and explore potential therapeutic applications of these CPE.

    Research area: Infection biology

    Dr. rer. nat. Christian Rüter (since 07/2016)

    Funding period: July 2012 - June 2020

    • Publications

      Original articles

      • Bielaszewska M, Greune L, Bauwens A, Dersch P, Mellmann A,  Rüter C (2021) Virulence Factor Cargo and Host Cell Interactions of Shiga Toxin-Producing Escherichia coli Outer Membrane Vesicles. Methods Mol Biol 2291:177-205

      • Chaoprasid P, Lukat P, Mühlen S, Heidler T, Gazdag EM, Dong S, Bi W, Rüter C, Kirchenwitz M, Steffen A, Jänsch L, Stradal T, Dersch P, Wulf Blankenfeldt W (2021) Crystal structure of full-length cytotoxic necrotizing factor CNFY reveals molecular building blocks for intoxication. EMBO J 7:e105202

      • Rüter C, Bielaszewska M (2020) Secretion and Delivery of Intestinal Pathogenic Escherichia coli Virulence Factors via Outer Membrane Vesicles. Front Cell Infect Microbiol 10: 91

      • Baumann D., Salia H., Greune L., Norkowski S., Körner B., Uckeley Z.M., Frankel G., Guenot M., Rüter C., Schmidt M.A. (2018) Multitalented EspB of enteropathogenic E. coli (EPEC) enters cells autonomously and induces programmed cell death in THP-1 cells. Int. J. Med. Microbiol. 308:387–404.

      • Norkowski S., Schmidt M.A., and Rüter C. (2018) The species-spanning family of LPX-motif harboring effector proteins. Cell. Microbiol. 20(11):e12945.
      • Benjamin Grabowski, M. Alexander Schmidt & Christian Rüter (2017) Immunomodulatory Yersinia outer proteins (Yops)–useful tools for bacteria and humans alike, Virulence. (doi: 10.1080/21505594.2017.1303588)

      • GomarascaM., MartinsT.F.C., Greune L., Hardwidge P.R., Schmidt M.A., and RüterC. (2017) Bacterium-derived CPP deliver gentamicin to kill intracellular pathogens. Antimicrob. Agents Chemother. 61(4):e02545-16.

      • Norkowski S., Körner B., Greune L., Stolle A-S., Lubos M-L., Hardwidge P.R., Schmidt M.A. and Rüter C. (2017) Bacterial LPX motif-harboring virulence factors constitute a species-spanning family of cell-penetrating effectors. Cell. Mol. Life Sci. 75(12):2273–2289.
      • Stolle A-S, Norkowski S, Körner B, Schmitz J, Lüken L, Frankenberg M, Rüter C and Schmidt MA (2017) T3SS-Independent Uptake of the Short-Trip Toxin-Related Recombinant NleC Effector of Enteropathogenic Escherichia coli Leads to NF-κB p65 Cleavage. Front. Cell. Infect. Microbiol. 7:119. (doi: 10.3389/fcimb.2017.00119)
      • Cordes F, Brückner M, Lenz P, Veltman K, Glauben R, Siegmund B, Hengst K, Schmidt MA, Cichon Ch, Bettenworth D (2016) MicroRNA-320a strengthens intestinal barrier function and follows the course of experimental colitis. Inflamm Bowel Dis 22(10): 2341-2355. (doi 10.1097/MIB.0000000000000917)
      • Grabowski B, Rüter C, Schmidt MA (2017) Immunomodulatory Yersinia outer proteins (Yops) – useful tools for bacteria and humans alike. Virulence (doi 10.1080/21505594.2017.1303588)
      • Höfling S, Grabowski B, Norkowski S, Schmidt MA, Rüter C. (2015) Current activities of the Yersinia effector protein YopM. Int J Med Microbiol., Apr 1., pii: S1438-4221(15)00028-4. doi: 10.1016/j.ijmm.2015.03.009. [Epub ahead of print] PMID:25865799
      • Lubos M-L, Norkowski S, Stolle A-S, Langel Ü, Schmidt MA, Rüter C (2014) Analysis of T3SS-independent autonomous internalization of the bacterial effector protein SspH1 from Salmonella typhimurium. Inflammation & Cell Signaling 1: e423. [doi: 10.14800/ics.423]
      • Rüter C, Ruiz Silva M, Grabowski B, Lubos M-L, Scharnert J, Poceva M, von Tils D, Flieger A, Heesemann J, Bliska JB, Schmidt MA (2014) Rabbit monoclonal antibodies directed at the T3SS effector protein YopM identify human pathogenic Yersinia isolates. Int J Med Microbiol 304: 444–451.
      • Bielaszewska M, Rüter C, Kunsmann L, Greune L, Bauwens A, Zhang W, Kuczius T, Kim KS, Mellmann A, Schmidt MA, Karch H (2013) Enterohemorrhagic Escherichia coli hemolysin employs outer membrane vesicles to target mitochondria and cause endothelial and epithelial apoptosis. PLoS Pathog 9: e1003797. doi: 10.1371/journal.ppat.1003797.
      • Rüter C, Hardwidge PR (2013) 'Drugs from Bugs': bacterial effector proteins as promising biological (immune-) therapeutics. FEMS Microbiol Lett 351: 126-132. (cover)

      Reviews

      • Rüter C., and Schmidt M.A. (2017) Cell-Penetrating Bacterial Effector Proteins: Better Tools than Targets. Trends in Biotechnology. 35(2):109-120.