Genetic basis involved in host interaction and adaptation of Escherichia coli: Impact on crosstalk with cellular barriers

    We aim at the identification of bacterial properties and the molecular mechanisms involved in different types of host-bacterium interaction at cellular barriers leading to infection or colonization. We want to unravel how bacteria downregulate RNA polymerase II and c-MYC-dependent host gene expression. We also want to understand how epigenetic mechanisms, like histone acetylation and DNA methylation, reprogramme innate immunity during infection with uropathogenic E. coli.

    Research area: Bacterial genetics, infection biology

    Prof. Dr. rer. nat. Ulrich Dobrindt

    Funding period: July 2012 - June 2024

    • Publications

      Original articles

      • Ambite I, Filenko NA, Zaldastanishvili E, Butler DS, Tran TH, Chaudhuri A, Esmaeili P, Ahmadi S, Paul S, Wullt B, Putze J, Chen SL, Dobrindt U, Svanborg C (2021) Active bacterial modification of the host environment through RNA polymerase II inhibition. J Clin Invest 131(4):e140333
      • Butler DSC, Cafaro C, Putze J, Wan MLY, Tran TH, Ambite I, Ahmadi S, Kjellström S, Welinder C, Chao SM, Dobrindt U, Svanborg C (2021) A bacterial protease depletes c-MYC and increases survival in mouse models of bladder and colon cancer. Nat Biotechnol. doi: 10.1038/s41587-020-00805-3
      • Bano L, Kiel M, Sales G, Doxey AC, Mansfield MJ, Wami HT, Schiavone M, Rossetto O, Pirazzini M, Dobrindt U, Montecucco C (2020) Genome Sequence of the Fish Brain Bacterium Clostridium tarantellae. Microbiol Resour Announc 9(16):e01575-19
      • 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
      • Kalsy M, Tonk M, Hardt M, Dobrindt U, Zdybicka-Barabas A, Cytrynska M, Vilcinskas A, Mukherjee K (2020) The insect antimicrobial peptide cecropin A disrupts uropathogenic Escherichia coli biofilms. NPJ Biofilms Microbiomes 6(1):6
      • Leite Dantas R, Bettenworth D, Varga G, Weinhage T, Wami HT, Dobrindt U, Roth J, Vogl T, Ludwig S, Wixler V. (2020) Spontaneous onset of TNFα-triggered colonic inflammation depends on functional T lymphocytes, S100A8/A9 alarmins, and MHC H-2 haplotype. J Pathol 251(4):388-399
      • Mukherjee K, Amsel D, Kalsy M, Billion A, Dobrindt U, Vilcinskas A (2020) MicroRNAs regulate innate immunity against uropathogenic and commensal-like Escherichia coli infections in the surrogate insect model Galleria mellonella. Sci Rep 10(1):2570
      • Legros N, Ptaschek S, Pohlentz G, Karch H, Dobrindt U, Müthing J (2019) PapG Subtype-Specific Binding Characteristics of Escherichia coli Towards Globo-Series Glycosphingolipids of Human Kidney and Bladder Uroepithelial Cells. Glycobiology pii:cwz059.
      • Stork C, Kovács B, Rózsai B, Putze J, Kiel M, Dorn A, Kovács J, Melegh S, Leimbach A, Kovács T, Schneider G, Kerényi M, Emödy L, Dobrindt U (2018b) Characterization of asymptomatic E. coli bacteriuria isolates in search of alternative strains for efficient bacterial interference against uropathogens. Frontiers Microbiol 9:214.
      • Bielaszewska M, Rüter C, Bauwens A, Greune L, Jarosch AK, Steil D, Zhang W, He X, Lloubes R, Fruth A, Kim KS, Schmidt MA, 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:e1006159.
      • Galstyan A, Schiller R, Dobrindt U (2017b) Boronic Acid-Functionalized Photosensitizers: a Strategy to Target the Surface of Bacteria and Implement Active Agents in Polymer Coatings. Angew Chem Int Ed Engl 56:10362-10366.
      • Münzner P, Kengmo Tchoupa A, Klauser B, Putze J, Brunner T, Dobrindt U, Hauck CR (2016) Uropathogenic E. coli exploit CEA to promote colonization of the urogenital tract mucosa. PLoS Pathogens 12:e1005608.
      • Heitmueller M, Billion A, Dobrindt U, Vilcinskas A, Mukherjee K. (2017) Epigenetic Mechanisms Regulate Innate Immunity against Uropathogenic and Commensal-Like Escherichia coli in the Surrogate Insect Model Galleria mellonella. Infect Immun. 85(10). pii: e00336-17. (doi: 10.1128/IAI.00336-17)
      • Galstyan A, Putze J, Dobrindt U (2017) Striking an access to the bacteria via (reversible) control of lipophilicity.Chemistry. doi: 10.1002/chem.201704562.
      • Galstyan A, Schiller R, Dobrindt U. (2017) Boronic Acid Functionalized Photosensitizers: A Strategy to Target the Surface of Bacteria and Implement Active Agents in Polymer Coatings. Angew Chem Int Ed Engl. 56(35):10362-10366. (doi: 10.1002/anie.201703398)
      • Thölking G, Schuette-Nuetgen K, Vogl T, Dobrindt U, Kahl BC, Brand M, Pavenstädt H, Suwelack B, Koch R, Reuter S. (2017) Male kidney allograft recipients at risk for urinary tract infection? PLoS One 12(11):e0188262. doi: 10.1371/journal.pone.0188262.
      • Wiegand S, Zakrzewski SS, Eichner M, Schulz E, Günzel D, Pieper R, Rosenthal R, Barmeyer C, Bleich A, Dobrindt U, Schulzke JD, Bücker R. (2017) Zinc treatment is efficient against Escherichia coli α-haemolysin-induced intestinal leakage in mice. Sci Rep. 7:45649. (doi: 10.1038/srep45649)
      • Ambite I, Lutay N, Stork C, Dobrindt U, Wollt B, Svanborg C (2016) Bacterial suppression of RNA polymerase II-dependent host gene expression. Pathogens 5: 49. (doi:10.3390/pathogens5030049) 
      • Dobrindt U, Wullt B, Svanborg C (2016) Asymtomatic Bacteriuria as a Model to Study the Coevolution of Hosts and Bacteria. Pathogens 5:21.
      • Muenzner P, Kengmo Tchoupa A, Klauser B, Brunner T, Putze J, Dobrindt U, Hauck CR (2016) Uropathogenic E. coli exploit CEA to promote colonization of the urogenital tract mucosa. PLoS Pathog 12(5): e1005608. (doi:10.1371/journal. ppat.1005608) 
      • Starost LJ, Karassek S, Sano Y, Kanda T, Kim KS, Dobrindt U, Rüter C, Schmidt MA (2016) Pertussis Toxin Exploits Host Cell Signaling Pathways Induced by Meningitis-Causing E. coli K1-RS218 and Enhances Adherence of Monocytic THP-1 Cells to Human Cerebral Endothelial Cells. Toxins 8:E291.
      • 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, Lammers L, Bauwens A, Fruth A, Middendorf B, Schmidt MA, Tarr PIT, Dobrindt U, Karch H, Mellmann M (2014) Heteropathogenic virulence and phylogeny reveal phased pathogenic metamorphosis in Escherichia coli O2:H6. EMBO Mol Med 6(3): 347-357.
      • Köves B, Salvador E, Grönberg-Hernandez J, Zdziarski J, Wullt B, Svanborg C, Dobrindt U (2014) Rare emergence of symptoms during long-term asymptomatic E. coli 83972 carriage, without altered virulence factor repertoire. J Urol 191: 519-528. doi:10.1016/j.juro.2013.07.060.
      • Revelles O, Millard P, Nougayrède J-P, Dobrindt U, Oswald E, Létisse F, Portais J-C (2013) The Carbon storage regulator (Csr) system exerts a nutrient-specific control over central metabolism in Escherichia coli strain Nissle 1917. PLoS One 8: e66386
      • Sváb D, Horváth B, Maróti G, Dobrindt U, Tóth I (2013) Sequence variability of P2-like prophage genomes carrying the cytolethal distending toxin V operon in Escherichia coli O157. Appl Environ Microbiol 79: 4958-4964.
      Book articles
      • Rehm N, Berger M, Dobrindt U (2016) Bacterial Genome Plasticity. In: Encyclopedia of Evolutionary Biology (R.M. Kliman, ed.) Elsevier Amsterdam, in press.
      • Dobrindt U, Tjaden S, Shah S, Hacker J (2015b) Mobile genetic elements and pathogenicity islands encoding bacterial toxins. In: The Comprehensive Sourcebook of Bacterial Protein Toxins (Alouf, J., Ladant, D., Popoff, M. eds.) Elsevier Amsterdam, 40-76.