title: Using a bacteriocin structure to engineer a phage lysin that targets Yersinia pestis.
abstract: Purified phage lysins present an alternative to traditional antibiotics and work by hydrolysing peptidoglycan. Phage lysins have been developed against Gram-positive pathogens such as Bacillus anthracis and Streptococcus pneumoniae, where the peptidoglycan layer is exposed on the cell surface. Addition of the lysin to a bacterial culture results in rapid death of the organism. Gram-negative bacteria are resistant to phage lysins because they contain an outer membrane that protects the peptidoglycan from degradation. We solved crystal structures of a Yersinia pestis outer-membrane protein and the bacteriocin that targets it, which informed engineering of a bacterial-phage hybrid lysin that can be transported across the outer membrane to kill specific Gram-negative bacteria. This work provides a template for engineering phage lysins against a wide variety of bacterial pathogens.
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Petra
authors.initials: P
authors.lastname: Lukacik
authors.forename: Travis J
authors.initials: TJ
authors.lastname: Barnard
authors.forename: Susan K
authors.initials: SK
authors.lastname: Buchanan
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D001426:Bacterial Proteins / Q000378:metabolism; D001430:Bacteriocins / Q000737:chemistry* / Q000235:genetics; D001435:Bacteriophages / Q000201:enzymology; D015195:Drug Design; D008958:Models, Molecular; D011487:Protein Conformation; D015202:Protein Engineering; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000378:metabolism; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology; D015010:Yersinia pestis / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001430:Bacteriocins; C090748:FyuA protein, Yersinia; D011956:Receptors, Cell Surface; D014764:Viral Proteins