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In vitro and in vivo effect of immunoglobulin G on the integrity of bacterial membranes

In vitro- und In vivo-Effekte von Immunglobulin G auf die Integrität bakterieller Membranen

  • The Sixth Sils Maria Symposium Non-Antibiotic Prevention And Treatment Of Infectious Diseases
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Summary

The interaction between a modified 7S immunoglobulin (MISG) and bacterial membranes was studied by adoptingin vitro as well asin vivo techniques. Preincubation ofEscherichia coli andPseudomonas aeruginosa with MISG resulted in a release of enzymatic markers from the periplasmic space, whereas no cytoplasmic or membrane-bound enzymes were liberated. Due to the interaction of MISG with the outer membrane of gram-negative rods, the bacteria became more susceptible to the antibacterial action of poorly penetrating penicillins because of a significantly increased rate of uptake. Thesein vitro effects were corroborated underin vivo conditions by adopting the granuloma pouch model. A single intravenous injection of MISG enhanced the therapeutic efficacy of mezlocillin againstE. coli; similarly, the antibacterial activity of penicillin G, oxacillin, cephalothin and cefamandole againstStaphylococcus aureus was augmented by MISG. Thesein vivo effects of MISG were not due to an increased rate of phagocytosis or complement activity. Thus, MISG sensitized bacteria to several β-lactam antibiotics by disorganizing their outer membrane.

Zusammenfassung

Die Interaktion zwischen einem modifizierten 7S Immunserumglobulin (MISG) und bakteriellen Membranen wurde sowohl unterIn vitro- als auchIn vivo-Bedingungen geprüft. Eine Präinkubation vonEscherichia coli undPseudomonas aeruginosa mit MISG resultierte in der Freisetzung von Enzymmarkern aus dem periplasmatischen Raum, wohingegen keine zytoplasmatischen oder zellwandgebundenen Enzyme freigesetzt wurden. Aufgrund der Interaktion von MISG mit der äußeren Membran gram-negativer Stäbchen wurden diese Bakterien empfindlicher gegenüber der antibakteriellen Wirkung von nur geringradig penetrierenden Penicillinen, da ihre Aufnahmerate signifikant erhöht wurde. DieseIn vitro-Effekte wurden auch unterIn vivo-Bedingungen unter Verwendung des Granuloma-Pouch Modells bestätigt. Eine einzige intravenöse MISG-Injektion erhöhte die therapeutische Effektivität von Mezlocillin gegenüberE. coli; in ähnlicher Weise wurde die antibakterielle Effektivität von Penicillin G, Oxacillin, Cephalothin und Cefamandol gegenüberStaphylococcus aureus durch MISG gesteigert. DieseIn vivo-Effekte sind nicht auf eine gesteigerte Phagozytoserate oder erhöhte Komplementaktivität zurückzuführen. Somit sensitiviert MISG Bakterien gegenüber mehreren β-Laktamantibiotika aufgrund einer Desintegration der äußeren Membran.

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  1. Bayer AG, Pharma Research Centre, Institute for Chemotherapy, P.O. Box 10 17 09, D-5600, Wuppertal 1

    A. Dalhoff

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Dalhoff, A. In vitro and in vivo effect of immunoglobulin G on the integrity of bacterial membranes. Infection 12, 214–220 (1984). https://doi.org/10.1007/BF01640908

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