Use of a Bacteriophage Lysin to Identify a Novel Target for Antimicrobial Development
| Autor: | Bhaskaran Shyam S, Adam J. Pelzek, Yong Xu, C. Erec Stebbins, Patricia Ryan, Hariprasad Vankayalapati, David J. Bearss, Andrew Farnsworth, Raymond Schuch, Assaf Raz, Vincent A. Fischetti, Allan R. Goldberg, Chad W. Euler, Benjamin Y. Winer, Adrienne Clifford |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Mouse
Receptor expression Applied Microbiology Cell Lysin lcsh:Medicine Epimerox Biochemistry Polymerase Chain Reaction Bacterial cell structure Bacteriophage chemistry.chemical_compound Mice Mucoproteins Anti-Infective Agents Drug Discovery Bacteriophages lcsh:Science Receptor Staphylococci 0303 health sciences Multidisciplinary biology Animal Models Bacillus anthracis Bacterial Pathogens Bacterial Biochemistry medicine.anatomical_structure Medicine Female Research Article Biotechnology Drugs and Devices Drug Research and Development Microbial Sensitivity Tests Microbiology 03 medical and health sciences Model Organisms Virology medicine Animals Biology Microbial Pathogens 030304 developmental biology DNA Primers Gram Positive 030306 microbiology lcsh:R Bacteriology biology.organism_classification Mice Inbred C57BL Animal Models of Infection chemistry Small Molecules lcsh:Q |
| Zdroj: | PLoS ONE PLoS ONE, Vol 8, Iss 4, p e60754 (2013) |
| ISSN: | 1932-6203 |
| Popis: | We identified an essential cell wall biosynthetic enzyme in Bacillus anthracis and an inhibitor thereof to which the organism did not spontaneously evolve measurable resistance. This work is based on the exquisite binding specificity of bacteriophage-encoded cell wall-hydrolytic lysins, which have evolved to recognize critical receptors within the bacterial cell wall. Focusing on the B. anthracis-specific PlyG lysin, we first identified its unique cell wall receptor and cognate biosynthetic pathway. Within this pathway, one biosynthetic enzyme, 2-epimerase, was required for both PlyG receptor expression and bacterial growth. The 2-epimerase was used to design a small-molecule inhibitor, epimerox. Epimerox prevented growth of several Gram-positive pathogens and rescued mice challenged with lethal doses of B. anthracis. Importantly, resistance to epimerox was not detected ( |
| Databáze: | OpenAIRE |
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