Roles of the CNFY toxin for Yersinia pseudotuberculosis for crossing intestinal barriers, colonization of subepithelial tissue and pathology

    CNFY of Yersinia pseudotuberculosis is a key virulence factor that triggers the activation of Rho GTPases, which control cytoskeletal dynamics in phagocytes and contributes significantly to the induction of inflammatory responses and formation of necrosis in intestinal lymphoid tissues. The underlying mechanisms, however, are still unclear. We will therefore (i) analyze how the CNFY toxin modulates cell barrier functions and influences cellular penetration processes, and (ii) will characterize the influence of CNFY on targeted immune cells and the induction of inflammatory responses, phagocytosis and cell death. This will help us to evaluate potential host factors counteracting CNFY -triggered detrimental inflammatory responses and tissue destruction.

    Principal investigator:

    Prof. Dr. rer. nat. Petra Dersch

    Funding period:  July 2020  -  June 2024


    • 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
      • Heine W, Beckstette M, Heroven AK, Thiemann S, Heise U, Nuss AM, Pisano F, Strowig T, and Dersch P. (2018) Loss of CNFY toxin-induced inflammation drives Yersinia pseudotuberculosis into persistency. PLoS Pathog. 14(2): e1006858.
      • Nuss AM*, Beckstette M*, Pimenova M, Schmühl C, Opitz W, Pisano F, Heroven AK, Dersch P. (2017) Tissue dual RNA-seq allows fast discovery of infection-specific functions and riboregulators shaping host-pathogen transcriptome. Proc. Natl. Acad. Sci. USA. 114(5): E791-E800 etc.
      • Pezoldt J+, Pisano F +, Heine W, Pasztoi M, Rosenheinrich M, Nuss AM, Pils MC, Prinz I, Förster R, Huehn J, Dersch P*. Impact of CCR7 on T-cell response and susceptibility to Yersinia pseudotuberculosis infection. J. Infect. Dis. 2017; 216: 752-760.
      • Avican K, Fahlgren A, Heroven AK, Huss M, Beckstette M, Dersch P, Fällman M. Re­programming of Yersinia from virulent to persistent mode revealed by complex in vivo RNA-seq analysis. PLoS Pathog. 2015; 11: e1004600.
      • Schweer J, Kulkarni D, Kochut A, Pezoldt J, Pisano F, Pils MC, Genth H, Huehn J, Dersch P. The cytotoxic necrotizing factor of Yersinia pseudotuberculosis (CNFY) enhances inflammation and Yop delivery during infection by activation of Rho GTPases. PLoS Pathog. 2013; 9(11): e1003746.
      • Pasztoi M., Kulkarni D., Bonifacius A., Niemz J., Pezoldt J., Teich R., Prinz I., Rohde M., Pisano F., Dersch P., Huehn J. Yersinia pseudotuberculosis supports Th17 differentiation and limits de novo regulatory T cell induction by directly interfering with T cell receptor signaling (2017) Cellular and Molecular Life Sciences 74(15):2839-2850.
      • Elfiky A., Bonifacius A., Pezoldt J., Pasztoi M., Chaoprasid P., Sadana P., El-Sherbeeny N., Hagras M, Scrima A., Dersch P., Huehn J. (2018) Yersinia pseudotuberculosis modulates regu­latory T cell stability via injection of Yersinia outer proteins in a type III secretion system-de­pendent manner. European Journal of Microbiology and Immunology 8(4), 101-106.