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    Extending the Host Range of Listeria Monocytogenes by Rational Protein Design (2007)

    Art
    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Autoren
    Wollert, Thomas
    Pasche, Bastian
    Rochon, Maike
    Deppenmeier, Stefanie
    van den Heuvel, Joop
    Gruber, Achim D
    Heinz, Dirk W
    Lengeling, Andreas
    Schubert, Wolf-Dieter
    Quelle
    Cell; 129(5) — S. 891–902
    ISSN: 0092-8674
    Sprache
    Englisch
    Verweise
    Pubmed: 17540170
    Kontakt
    Institut für Tierpathologie

    Robert-von-Ostertag-Str. 15
    Gebäude 12
    14163 Berlin
    Tel.+49 30 838 62450 Fax.+49 30 838 62522

    Abstract / Zusammenfassung

    In causing disease, pathogens outmaneuver host defenses through a dedicated arsenal of virulence determinants that specifically bind or modify individual host molecules. This dedication limits the intruder to a defined range of hosts. Newly emerging diseases mostly involve existing pathogens whose arsenal has been altered to allow them to infect previously inaccessible hosts. We have emulated this chance occurrence by extending the host range accessible to the human pathogen Listeria monocytogenes by the intestinal route to include the mouse. Analyzing the recognition complex of the listerial invasion protein InlA and its human receptor E-cadherin, we postulated and verified amino acid substitutions in InlA to increase its affinity for E-cadherin. Two single substitutions increase binding affinity by four orders of magnitude and extend binding specificity to include formerly incompatible murine E-cadherin. By rationally adapting a single protein, we thus create a versatile murine model of human listeriosis.