Autopenetration bakterieller Effektorproteine und die Modulation der Signalwege in zellulären Barrieren

    Wir konnten zahlreiche T3SS-abhängige Effektoren Gram-negativer Pathogene als ’zell-penetrierende Effektorproteine (CPE)’ identifizieren. CPE aus E. coliYersinia und Shigella werden hinsichtlich ihrer Aufnahme, des intrazellulären ’traffickings’, der Modulation zellulärer Signalwege, der Möglichkeiten des Transports heterologen cargos und ihres Effekts auf zelluläre Barrieren (2-D und 3-D) mit und ohne ’shear stress’ charakterisiert. Zusätzlich untersuchen wir therapeutische Wirkungen in verschiedenen Modellen für Autoimmunkrankheiten in der Maus.

    Forschungsgebiet: Infektionsbiologie

    Dr. rer. nat. Christian Rüter                        (07/2016 - 06/2024)
    Prof. Dr. rer. nat. M. Alexander Schmidt    (07/2012 - 06/2020)

    Projektlaufzeit: Juli 2012 - Juni 2024

    • Publikationen

      Originalartikel

      • 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.