title: Novel phage lysin capable of killing the multidrug-resistant gram-negative bacterium Acinetobacter baumannii in a mouse bacteremia model.
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.
authors.affiliation: Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, New York, New York, USA.
authors.forename: Rolf
authors.initials: R
authors.lastname: Lood
authors.affiliation: Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, New York, New York, USA.
authors.forename: Benjamin Y
authors.initials: BY
authors.lastname: Winer
authors.affiliation: Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, New York, New York, USA.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Pelzek
authors.affiliation: Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, New York, New York, USA Molecular Microbiology and Infection Biology Department, Host-Parasite Interplay in Pneumococcal Infection Group, Centro de Investigaciones Biológicas, Madrid, Spain.
authors.forename: Roberto
authors.initials: R
authors.lastname: Diez-Martinez
authors.affiliation: Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, New York, New York, USA.
authors.forename: Mya
authors.initials: M
authors.lastname: Thandar
authors.affiliation: Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, New York, New York, USA Department of Medical Laboratory Sciences, School of Arts and Sciences, Hunter College, CUNY, New York, New York, USA.
authors.forename: Chad W
authors.initials: CW
authors.lastname: Euler
authors.affiliation: Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, New York, New York, USA.
authors.forename: Raymond
authors.initials: R
authors.lastname: Schuch
authors.affiliation: Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, New York, New York, USA vaf@rockefeller.edu.
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Fischetti
mesh_terms: D000151:Acinetobacter Infections / Q000188:drug therapy* / Q000382:microbiology; D040981:Acinetobacter baumannii / Q000187:drug effects*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D016470:Bacteremia / Q000188:drug therapy* / Q000382:microbiology; D018441:Biofilms / Q000187:drug effects; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008826:Microbial Sensitivity Tests; D009113:Muramidase / Q000494:pharmacology; D018805:Sepsis / Q000188:drug therapy / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D009113:Muramidase