Title |
Use of a Bacteriophage Lysin to Identify a Novel Target for Antimicrobial Development
|
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Published in |
PLOS ONE, April 2013
|
DOI | 10.1371/journal.pone.0060754 |
Pubmed ID | |
Authors |
Raymond Schuch, Adam J. Pelzek, Assaf Raz, Chad W. Euler, Patricia A. Ryan, Benjamin Y. Winer, Andrew Farnsworth, Shyam S. Bhaskaran, C. Erec Stebbins, Yong Xu, Adrienne Clifford, David J. Bearss, Hariprasad Vankayalapati, Allan R. Goldberg, Vincent A. Fischetti |
Abstract |
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 (<10(-11) frequency) in B. anthracis and S. aureus. These results describe the use of phage lysins to identify promising lead molecules with reduced resistance potential for antimicrobial development. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 6 | 32% |
United Kingdom | 2 | 11% |
Chile | 2 | 11% |
Honduras | 1 | 5% |
Mexico | 1 | 5% |
Unknown | 7 | 37% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 14 | 74% |
Scientists | 4 | 21% |
Practitioners (doctors, other healthcare professionals) | 1 | 5% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 2 | 2% |
Nepal | 1 | <1% |
Indonesia | 1 | <1% |
Germany | 1 | <1% |
Ireland | 1 | <1% |
South Africa | 1 | <1% |
United Kingdom | 1 | <1% |
France | 1 | <1% |
Belgium | 1 | <1% |
Other | 3 | 3% |
Unknown | 102 | 89% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 31 | 27% |
Researcher | 24 | 21% |
Student > Bachelor | 14 | 12% |
Student > Master | 13 | 11% |
Other | 5 | 4% |
Other | 16 | 14% |
Unknown | 12 | 10% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 49 | 43% |
Immunology and Microbiology | 11 | 10% |
Medicine and Dentistry | 11 | 10% |
Biochemistry, Genetics and Molecular Biology | 10 | 9% |
Chemistry | 4 | 3% |
Other | 18 | 16% |
Unknown | 12 | 10% |