für 0,5 h mit dem EPEC Protein NleC (grün) inkubierte und mit IL1b stimulierte HeLa-Zellen
© A. S. Stolle
HeLa, YopH / Rab7 Co-Staining (6h) | HeLa, YopH / CD63 Co-Staining (24h)
© B. Grabowski

    Autopenetration bakterieller Effektorproteine und die Modulation der Signalwege in zellulären Barrieren

    Effektorproteine können unabhängig vom Typ III-Sekretionssystem (T3SS) in Wirtszellen eindringen und so ihren potentiellen Funktionsbereich auch auf zelluläre Barrieren erweitern. Hierzu konnten wir die gesamte Gruppe der bakteriellen Effektoren mit Leucin-reichen Wiederholungen (LPX) als bislang unbekannte zell-penetrierende Effektoren (CPE) identifizieren. Nun wollen wir die Auswirkungen dieser neuen Klasse von CPE auf die Modulation von Immunantworten in Zellkultur- und Tier- Modellen genauer untersuchen und so mögliche therapeutische Anwendungen dieser CPE erforschen.

    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

      • Bäumer N, Scheller A, Wittmann L, Faust A, Apel M, Nimmagadda SC, Geyer C, Grunert K, Kellmann N, Peipp M, Kailayangiri S, Gutierrez Suburu ME, Strassert CA, Schenk M, Greune L, Rüter C, Dersch P, Hartmann W, Rössig C, Neri D, Müller-Tidow C, Schwöppe C, Schliemann C, Khandanpour C, Lenz G, Berdel WE, Bäumer S (2022) Electrostatic anti-CD33-antibody-protamine nanocarriers as platform for a targeted treatment of acute myeloid leukemia. J Hematol Oncol. 15(1): 171. doi:10.1186/s13045-022-01390-5

      • Bäumer N, Tiemann J, Scheller A, Meyer T, Wittmann L, Suburu MEG, Greune L, Peipp M, Kellmann N, Gumnior A, Brand C, Hartmann W, Rössig C, Müller-Tidow C, Neri D, Strassert CA, Rüter C, Dersch P, Lenz G, Koeffler HP, Berdel WE, Bäumer S (2022) Targeted siRNA nanocarrier: a platform technology for cancer treatment. Oncogene. 41(15):2210-2224. doi:10.1038/s41388-022-02241-w

      • Faust A, Bäumer N, Schlütermann A, Becht M, Greune L, Geyer C, Rüter C, Margeta R, Wittmann L, Dersch P, Lenz G, Berdel WE, Bäumer S (2022) Tumor-cell-specific targeting of Ibrutinib: Introducing electrostatic antibody-inhibitor conjugates (AiCs). Angew Chem Int Ed Engl. 61(1):e202109769.  doi:10.1002/anie.202109769

      • Rüter C (2022) Delivery of antibiotics by cell-penetrating peptides to kill intracellular pathogens. Methods Mol Biol 2383: 335-345. doi:10.1007/978-1-0716-1752-6_22"

      • 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

      • 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.