The bacterial secreted combinome: Synergistic host injury by exotoxins of enterohemorrhagic Escherichia coli

    Enterohemorrhagic Escherichia coli (EHEC) secrete a cocktail of exotoxins, which in concert breach the intestinal epithelial and endothelial barrier, and cause severe complications such as the hemolytic uremic syndrome. This project is aimed at unraveling the interplay of virulence factors of EHEC serotypes O157:H- and O104:H4 and the role that host factors play in this process. Understanding the interactions of the individual determinants could form the basis for developing preventive and specific therapeutic measures for EHEC infections.

    Research area: Infection biology, pathogenesis

    Prof. Dr. med. Alexander Mellmann

    Funding period: July 2012 - 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
      • Bielaszewska M, Daniel O, Karch- H, Mellmann A (2020) Dissemination of the blaCTX-M-15 gene among Enterobacteriaceae via outer membrane vesicles. The Journal of antimicrobial chemotherapy 75(9), 2442–2451
      • Detzner J, Steil D, Pohlentz G, Legros N, Humpf HU, Mellmann A, Karch H, Müthing J (2020) Real-time interaction analysis of Shiga toxins and membrane microdomains of primary human brain microvascular endothelial cells. Glycobiology. doi: 10.1093/glycob/cwz091
      • Gati NS, Middendorf-Bauchart B, Bletz S, Dobrindt U, Mellmann A (2019) Origin and Evolution of Hybrid Shiga Toxin-Producing and Uropathogenic Escherichia coli Strains of Sequence Type 141. Journal of clinical microbiology 58(1), e01309-19
      • Kehl A, Kuhn R, Detzner J, Steil D, Müthing J, Karch H, Mellmann A (2020) Modeling Native EHEC Outer Membrane Vesicles by Creating Synthetic Surrogates. Microorganisms 8(5), 673
      • Kouzel IU, Kehl A, Berger P, Liashkovich I, Steil D, Makalowski W, Suzuki Y, Pohlentz G, Karch H, Mellmann A, Müthing J (2020) RAB5A and TRAPPC6B are novel targets for Shiga toxin 2a inactivation in kidney epithelial cells. Sci Rep 18;10(1):4945
      • Berger, P., Kouzel, I.U., Berger, M., Haarmann, N., Dobrindt, U., Koudelka, G.B., and Mellmann, A. (2019) Carriage of Shiga toxin phage profoundly affects Escherichia coli gene expression and carbon source utilization. BMC Genomics 20, 504.
      • Bielaszewska, M., Marejkova, M., Bauwens, A., Kunsmann-Prokscha, L., Mellmann, A., and Karch, H. (2018) Enterohemorrhagic Escherichia coli O157 outer membrane vesicles induce interleukin 8 production in human intestinal epithelial cells by signaling via Toll-like receptors TLR4 and TLR5 and activation of the nuclear factor NF-?B. Int J Med Microbiol 308, 882-889.
      • Haarmann, N., Berger, M., Kouzel, I.U., Mellmann, A., and Berger, P. (2018) Comparative virulence characterization of the Shiga toxin phage-cured Escherichia coli O104:H4 and enteroaggregative Escherichia coli. Int J Med Microbiol 308, 912-920.
      • Kampmeier, S., Berger, M., Mellmann, A., Karch, H., and Berger, P. (2018) The 2011 German enterohemorrhagic Escherichia coli O104:H4 outbreak - The danger is still out there. Curr Top Microbiol Immunol 416, 117-148.
      • Steil, D., Pohlentz, G., Legros, N., Mormann, M., Mellmann, A., Karch, H., and Müthing, J. (2018) Combining mass spectrometry, surface acoustic wave interaction analysis, and cell viability assays for characterization of Shiga toxin subtypes of pathogenic Escherichia coli bacteria. Anal Chem 90, 8989-8997.
      • Bauwens A., Kunsmann L., Karch H., Mellmann A., Bielaszewska M. (2017) Antibiotic-mediated modulations of outer membrane vesicles in enterohemorrhagic Escherichia coli O104:H4 and O157:H7. Antimicrob Agents Chemother. 61(9):e00937-17. (doi: 10.1128/AAC.00937-17)
      • Bauwens A., Kunsmann L., Marejkova M., Zhang, W., Karch H., Bielaszewska M., et al. (2017) Intrahost milieu modulates production of outer membrane vesicles, vesicle-associated Shiga toxin 2a, and cytotoxicity in Escherichia coli O157:H7 and O104:H4. Environ Microbiol Rep. (doi:10.1111/1758-2229.12562.)
      • Bielaszewska M.*; Ruter, C.*; Bauwens, A.*; Greune, L.; Jarosch, K. A.; Steil, D.; Zhang, W.; He, X.; Lloubes, R.; Fruth, A.; Kim, K. S.; Schmidt, M. A.; Dobrindt, U.; Mellmann, A.; Karch, H. (2017) Host cell interactions of outer membrane vesicle-associated virulence factors of enterohemorrhagic Escherichia coli O157: Intracellular delivery, trafficking and mechanisms of cell injury. PLoS pathogens. 13(2):e1006159. (doi: 10.1371/journal.ppat.1006159)
      • Berger, P., Knodler, M., Forstner, K.U., Berger, M., Bertling, C., Sharma, C.M., Vogel, J., Karch, H., Dobrindt, U., and Mellmann, A (2016). The primary transcriptome of the Escherichia coli O104:H4 pAA plasmid and novel insights into its virulence gene expression and regulation. Sci Rep 6, 35307.
      • Kunsmann L, Rüter C, Bauwens A, Greune L, Glüder M, Kemper B, Fruth A, Wai SN, He X, Lloubes R, Schmidt MA, Dobrindt U, Mellmann A, Karch H, Bielaszewska M (2015) Virulence from vesicles: Novel mechanisms of host cell injury by Escherichia coli O104:H4 outbreak strain. Sci Rep 5: 13252.
      • Bielaszewska M, Schiller R, Lammer L, Bauwens A, Fruth A, Middendorf B, Schmidt MA, Tarr PI, Dobrindt U, Karch HMellmann A (2014) Heteropathogenic virulence and phylogeny reveal phased pathogenic metamorphosis in Escherichia coli O2:H6. EMBO Mol Med 6: 347-357. (IF 10,3)
      • 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. (IF 9,1)