Preclinical Assessment of Bacteriophage Therapy against Experimental Acinetobacter baumannii Lung Infection.

Autor: Wienhold SM; Division of Pulmonary Inflammation, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10115 Berlin, Germany., Brack MC; Division of Pulmonary Inflammation, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10115 Berlin, Germany.; Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10115 Berlin, Germany., Nouailles G; Division of Pulmonary Inflammation, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10115 Berlin, Germany., Krishnamoorthy G; Division of Pulmonary Inflammation, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10115 Berlin, Germany., Korf IHE; Department of Microorganisms, Leibniz Institute DSMZGerman Collection of Microorganisms and Cell Cultures, 38124 Braunschweig, Germany.; Department of Pharmaceutical Biotechnology, Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), 38124 Braunschweig, Germany., Seitz C; Department of Pharmaceutical Biotechnology, Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), 38124 Braunschweig, Germany., Wienecke S; Department of Pharmaceutical Biotechnology, Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), 38124 Braunschweig, Germany., Dietert K; Department of Veterinary Pathology, Freie Universität Berlin, 14163 Berlin, Germany.; Veterinary Centre for Resistance Research, Freie Universität Berlin, 14163 Berlin, Germany., Gurtner C; Department of Veterinary Pathology, Freie Universität Berlin, 14163 Berlin, Germany., Kershaw O; Department of Veterinary Pathology, Freie Universität Berlin, 14163 Berlin, Germany., Gruber AD; Department of Veterinary Pathology, Freie Universität Berlin, 14163 Berlin, Germany., Ross A; Department of Pharmaceutical Biotechnology, Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), 38124 Braunschweig, Germany., Ziehr H; Department of Pharmaceutical Biotechnology, Fraunhofer Institute for Toxicology and Experimental Medicine (ITEM), 38124 Braunschweig, Germany., Rohde M; Central Facility for Microscopy, Helmholtz-Centre for Infection Research (HZI), 38124 Braunschweig, Germany., Neudecker J; Department of General, Visceral, Vascular and Thoracic Surgery, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10115 Berlin, Germany., Lienau J; Division of Pulmonary Inflammation, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10115 Berlin, Germany., Suttorp N; Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10115 Berlin, Germany., Hippenstiel S; Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10115 Berlin, Germany., Hocke AC; Division of Pulmonary Inflammation, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10115 Berlin, Germany.; Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10115 Berlin, Germany., Rohde C; Department of Microorganisms, Leibniz Institute DSMZGerman Collection of Microorganisms and Cell Cultures, 38124 Braunschweig, Germany., Witzenrath M; Division of Pulmonary Inflammation, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10115 Berlin, Germany.; Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10115 Berlin, Germany.; German Center for Lung Research (DZL), Partner Site Charité, 10117 Berlin, Germany.
Jazyk: angličtina
Zdroj: Viruses [Viruses] 2021 Dec 24; Vol. 14 (1). Date of Electronic Publication: 2021 Dec 24.
DOI: 10.3390/v14010033
Abstrakt: Respiratory infections caused by multidrug-resistant Acinetobacter baumannii are difficult to treat and associated with high mortality among critically ill hospitalized patients. Bacteriophages (phages) eliminate pathogens with high host specificity and efficacy. However, the lack of appropriate preclinical experimental models hampers the progress of clinical development of phages as therapeutic agents. Therefore, we tested the efficacy of a purified lytic phage, vB_AbaM_Acibel004, against multidrug-resistant A. baumannii clinical isolate RUH 2037 infection in immunocompetent mice and a human lung tissue model. Sham- and A. baumannii -infected mice received a single-dose of phage or buffer via intratracheal aerosolization. Group-specific differences in bacterial burden, immune and clinical responses were compared. Phage-treated mice not only recovered faster from infection-associated hypothermia but also had lower pulmonary bacterial burden, lower lung permeability, and cytokine release. Histopathological examination revealed less inflammation with unaffected inflammatory cellular recruitment. No phage-specific adverse events were noted. Additionally, the bactericidal effect of the purified phage on A. baumannii was confirmed after single-dose treatment in an ex vivo human lung infection model. Taken together, our data suggest that the investigated phage has significant potential to treat multidrug-resistant A. baumannii infections and further support the development of appropriate methods for preclinical evaluation of antibacterial efficacy of phages.
Databáze: MEDLINE
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