Publikationsdatenbank

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

Bandzählung: 129

Heftzählung: 5

Seiten: 891 – 902

ISSN: 0092-8674

Sprache

Englisch

Verweise

Pubmed: 17540170

Kontakt

Institut für Tierpathologie

Robert-von-Ostertag-Str. 15
14163 Berlin
+49 30 838 62450
pathologie@vetmed.fu-berlin.de

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.