Novel Phage Lysin Capable of Killing the Multidrug-Resistant Gram-Negative Bacterium Acinetobacter baumannii in a Mouse Bacteremia Model |
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| Authors: | Rolf Lood Benjamin Y. Winer Adam J. Pelzek Roberto Diez-Martinez Mya Thandar Chad W. Euler Raymond Schuch Vincent A. Fischetti |
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| Affiliation: | aLaboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, New York, New York, USA;bMolecular Microbiology and Infection Biology Department, Host-Parasite Interplay in Pneumococcal Infection Group, Centro de Investigaciones Biológicas, Madrid, Spain;cDepartment of Medical Laboratory Sciences, School of Arts and Sciences, Hunter College, CUNY, New York, New York, USA |
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| Abstract: | Acinetobacter baumannii, a Gram-negative multidrug-resistant (MDR) bacterium, is now recognized as one of the more common nosocomial pathogens. Because most clinical isolates are found to be multidrug resistant, alternative therapies need to be developed to control this pathogen. We constructed a bacteriophage genomic library based on prophages induced from 13 A. baumannii strains and screened it for genes encoding bacteriolytic activity. Using this approach, we identified 21 distinct lysins with different activities and sequence diversity that were capable of killing A. baumannii. The lysin (PlyF307) displaying the greatest activity was further characterized and was shown to efficiently kill (>5-log-unit decrease) all tested A. baumannii clinical isolates. Treatment with PlyF307 was able to significantly reduce planktonic and biofilm A. baumannii both in vitro and in vivo. Finally, PlyF307 rescued mice from lethal A. baumannii bacteremia and as such represents the first highly active therapeutic lysin specific for Gram-negative organisms in an array of native lysins found in Acinetobacter phage. |
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