B05 - Rybniker

B05 - Mechanisms and consequences of inflammasome mediated mitochondrial impairment in Mycobacterium tuberculosis infected myeloid cells

Jan Rybniker

Clinic I for internal medicine, University of Cologne
Contact: jan.rybniker(at)uk-koeln.de
For more information visit: Rybniker lab

Abstract

Mycobacterium tuberculosis (Mtb) is a highly successful intracellular pathogen based on its ability to manipulate innate immunity countermeasures of its major host, the human macrophage. Lytic host cell death is essential for bacterial dissemination and represents an important research topic both mechanistically and from a therapeutic perspective. This project aims to study how Mtb modulates regulated cell death in myeloid cells and to address the functional role of different cell death pathways in Mtb infection.

Recent Publications

2024

Theobald S, Müller T, Lange D, Keck K, Rybniker J. The role of inflammasomes as central inflammatory hubs in Mycobacterium tuberculosis infection. Front. Immunol., 11 September 2024. doi.org/10.3389/fimmu.2024.1436676 (Review)

Suárez I, Rauschning D, Schüller C, Hagemeier A, Stecher M, Lehmann C, Schommers P, Schlabe S, Vehreschild JJ, Koll C, Schwarze-Zander C, Wasmuth JC, Klingmüller A, Rockstroh JK, Fätkenheuer G, Boesecke C, Rybniker J. Incidence and risk factors for HIV-tuberculosis coinfection in the Cologne-Bonn region: a retrospective cohort study. Infection. 2024 Aug;52(4):1439-1448. doi: 10.1007/s15010-024-02215-y. Epub 2024 Mar 16. PMID: 38492196; PMCID: PMC11289312.

Albert MC, Uranga-Murillo I, Arias M, De Miguel D, Peña N, Montinaro A, Varanda AB, Theobald SJ, Areso I, Saggau J, Koch M, Liccardi G, Peltzer N, Rybniker J, Hurtado-Guerrero R, Merino P, Monzón M, Badiola JJ, Reindl-Schwaighofer R, Sanz-Pamplona R, Cebollada-Solanas A, Megyesfalvi Z, Dome B, Secrier M, Hartmann B, Bergmann M, Pardo J, Walczak H. Identification of FasL as a crucial host factor driving COVID-19 pathology and lethality. Cell Death Differ. 2024 Mar 21. doi: 10.1038/s41418-024-01278-6. Epub ahead of print. PMID: 38514848

Knopf, J.D., Steigleder, S.S., Korn, F., Kühnle, N., Badenes, M., Tauber, M., Theobald, S.J., Rybniker, J., Adrain, C., and Lemberg, M.K.. (2024) RHBDL4-triggered downregulation of COPII adaptor protein TMED7 suppresses TLR4-mediated inflammatory signaling. Nat Commun. 15(1):1528. doi: 10.1038/s41467-024-45615-2.

Project B05 Publications 1st Funding Period 2020 - 2023

2023

Gries, R., Chhen, .J, van Gumpel, E., Theobald, S.J., Sonnenkalb, L., Utpatel, C., Metzen, F., Koch, M., Dallenga, T., Djaout, K., Baulard, A., Dal Molin, M., and Rybniker, J. (2023). Discovery of dual-active ethionamide boosters inhibiting the Mycobacteriumtuberculosis ESX-1 secretion system. Cell Chem Biol. S2451-9456(23)00436-1. doi: 10.1016/j.chembiol.2023.12.007. Epub ahead of print. PMID: 38181799.

Simonis, A., Kreer. C., Albus, A., Rox, K., Yuan, B., Holzmann, D., Wilms, J.A., Zuber, S., Kottege, L., Winter, S., Meyer, M., Schmitt, K., Gruell, H., Theobald, S.J., Hellmann, A.M., Meyer, C., Ercanoglu, M.S., Cramer, N., Munder, A., Hallek, M., Fätkenheuer, G., Koch, M., Seifert, H., Rietschel, E., Marlovits, T.C., van Koningsbruggen-Rietschel, S., Klein, F., and Rybniker, J. (2023). Discovery of highly neutralizing human antibodies targeting Pseudomonas aeruginosa. Cell. 186, 5098-5113.e19. doi: 10.1016/j.cell.2023.10.002.

Augustin, M., Heyn, F., Ullrich, S., Sandaradura de Silva, U., Albert, M.C., Linne, V., Schlotz, M., Schommers, P., Pracht, E., Horn, C., Suarez, I., Simonis, A., Picard, L.K., Zoufaly, A., Wenisch, C., Fätkenheuer, G., Gruell, H., Klein, F., Hallek, M., Walczak, H., Rybniker, J., Theobald S.J., and Lehmann C. (2023) Immunological fingerprint in coronavirus disease-19 convalescents with and without post-COVID syndrome. Front Med (Lausanne). 10, 1129288. doi: 10.3389/fmed.2023.1129288

2022

2021

Theobald, S.J., Gräb, J., Fritsch, M., Suárez, I., Eisfeld, H.S., Winter, S., Koch, M., Hölscher, C., Pasparakis, M., Kashkar, H., and Rybniker, J. (2021) Gasdermin D mediates host cell death but not interleukin-1β secretion in Mycobacterium tuberculosis-infected macrophages. Cell Death Discov. 7, 327 (2021). https://doi.org/10.1038/s41420-021-00716-5

Eisfeld, H.S., Simonis, A., Winter, S., Chhen, J., Ströh, L.J., Krey, T., Koch, M., Theobald, S.J., Rybniker, J. (2021). Viral Glycoproteins Induce NLRP3 Inflammasome Activation and Pyroptosis in Macrophages. Viruses 2021, 13, 2076. https://doi.org/10.3390/v13102076

Theobald, S.J., Simonis, A., Georgomanolis, T., Kreer, C., Zehner, M., Eisfeld, H.S., Albert, M.C., Chhen, J., Motameny, S., Erger, F., Fischer, J., Malin, J.J., Gräb, J., Winter, S., Pouikli, A., David, F., Böll, B., Koehler, P., Vanshylla, K., Gruell, H., Suárez, I., Hallek, M., Fätkenheuer, G., Jung, N., Cornely, O.A., Lehmann, C., Tessarz, P., Altmüller, J., Nürnberg, P., Kashkar, H., Klein, F., Koch, M., and Rybniker, J. (2021) Long-lived macrophage reprogramming drives spike protein-mediated inflammasome activation in COVID-19. EMBO Mol Med e14150https://doi.org/10.15252/emmm.202114150

Project related Publications

2014 - 2019

Grab J, Suarez I, van Gumpel E, Winter S, Schreiber F, Esser A, Holscher C, Fritsch M, Herb M, Schramm M, Wachsmuth L, Pallasch C, Pasparakis M, Kashkar H, and Rybniker J. (2019). Corticosteroids inhibit Mycobacterium tuberculosis-induced necrotic host cell death by abrogating mitochondrial membrane permeability transition. Nat. Commun. 10, 688.

Augustin M, Horn C, Koch J, Sandaradura de Silva U, Platten M, Nierhoff D, Suarez I, Chon SH, Rybniker J, and Lehmann C. 2019. Tracking Tregs: Translocation of CD49b/LAG-3(+) Type 1 T Regulatory Cells to the Gut-Associated Lymphoid Tissue of HIV(+) Patients. AIDS Res. Hum. Retroviruses 35, 247-250.

Herrmann, J.*, Rybniker, J.*, and Muller, R. (2017). Novel and revisited approaches in antituberculosis drug discovery. Curr. Opin. Biotechnol. 48, 94-101. (*shared first authorship)

Lou, Y., Rybniker, J., Sala, C., and Cole, S.T. (2017). EspC forms a filamentous structure in the cell envelope of Mycobacterium tuberculosis and impacts ESX-1 secretion. Mol. Microbiol. 103, 26-38.

Rybniker, J., Vocat, A., Sala, C., Busso, P., Pojer, F., Benjak, A., and Cole, S.T. (2015). Lansoprazole is an antituberculous prodrug targeting cytochrome bc1. Nat. Commun. 6, 7659.

Wassermann, R., Gulen, M.F., Sala, C., Perin, S.G., Lou, Y., Rybniker, J., Schmid-Burgk, J.L., Schmidt, T., Hornung, V., Cole, S.T, and Ablasser, A. (2015). Mycobacterium tuberculosis Differentially Activates cGAS- and Inflammasome-Dependent Intracellular Immune Responses through ESX-1. Cell Host Microbe 17, 799-810.

Rybniker, J., Chen, J.M., Sala, C., Hartkoorn, R.C., Vocat, A., Benjak, A., Boy-Rottger, S., Zhang, M., Szekely, R., Greff, Z., Orfi, L., Szabadkai, I., Pato, J., Keri, G., and Cole, S.T. (2014). Anticytolytic screen identifies inhibitors of mycobacterial virulence protein secretion. Cell Host Microbe 16, 538-548.

Rybniker, J., Pojer, F., Marienhagen, J., Kolly, G.S., Chen, J.M., van Gumpel, E., Hartmann, P., and Cole, S.T. (2014). The cysteine desulfurase IscS of Mycobacterium tuberculosis is involved in iron-sulfur cluster biogenesis and oxidative stress defence. Biochem. J. 459, 467-478.

Lechartier, B. *, Rybniker, J. *, Zumla, A., and Cole, S.T. (2014). Tuberculosis drug discovery in the post-post-genomic era. EMBO Mol. Med. 6, 158-168. (*shared first authorship)

Patents

Named inventors: Jan Rybniker, Stewart Cole; Title: “Benzothiophene and benzyloxybenzylidene and indoline derivatives as pharmaceutically active agents”, PCT/EP2015/071110 (ref 6.1416, 15.09.2014)
Named inventors: Jan Rybniker, Stewart Cole, Title: “Benzimidazole sulfide derivatives as pharmaceutically active agents”, EP15152650.6 (EPFL TTO ref 6.1441, 27.01.2015)

Both patents reached the national phase.

UNIVERSITÄT ZU KÖLN

Sonderforschungsbereich 1403