Science (American Association for the Advancement of Science), 2008-09, Vol.321 (5896), p.1673-1675
2008
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Details
- Autor(en) / Beteiligte
- Titel
- Inhibitor of FtsZ with Potent and Selective Anti-Staphylococcal Activity
- Ist Teil von
- Science (American Association for the Advancement of Science), 2008-09, Vol.321 (5896), p.1673-1675
- Ort / Verlag
- Washington, DC: American Association for the Advancement of Science
- Erscheinungsjahr
- 2008
- Quelle
- American Association for the Advancement of Science
- Beschreibungen/Notizen
- FtsZ is an essential bacterial guanosine triphosphatase and homolog of mammalian β-tubulin that polymerizes and assembles into a ring to initiate cell division. We have created a class of small synthetic antibacterials, exemplified by PC190723, which inhibits FtsZ and prevents cell division. PC190723 has potent and selective in vitro bactericidal activity against staphylococci, including methicillin- and multi-drug-resistant Staphylococcus aureus. The putative inhibitor-binding site of PC190723 was mapped to a region of FtsZ that is analogous to the Taxol-binding site of tubulin. PC190723 was efficacious in an in vivo model of infection, curing mice infected with a lethal dose of S. aureus. The data validate FtsZ as a target for antibacterial intervention and identify PC190723 as suitable for optimization into a new anti-staphylococcal therapy.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0036-8075eISSN: 1095-9203DOI: 10.1126/science.1159961Titel-ID: cdi_proquest_miscellaneous_743331757
- Format
- –
- Schlagworte
- Amino Acid Sequence, Animals, Anti-Bacterial Agents - pharmacology, Anti-Bacterial Agents - therapeutic use, Antibacterial agents, Antibacterials, Antibiotics, Antibiotics. Antiinfectious agents. Antiparasitic agents, Bacillus subtilis - chemistry, Bacillus subtilis - drug effects, Bacillus subtilis - genetics, Bacteria, Bacterial Proteins - antagonists & inhibitors, Bacterial Proteins - chemistry, Bacterial Proteins - genetics, Bacterial Proteins - metabolism, Benzamides, Binding Sites, Biochemistry, Biological and medical sciences, Biomedical research, Cell division, Cell Division - drug effects, Crystallography, X-Ray, Cytoskeletal Proteins - antagonists & inhibitors, Cytoskeletal Proteins - chemistry, Cytoskeletal Proteins - genetics, Cytoskeletal Proteins - metabolism, Drug discovery, Drug Resistance, Bacterial - genetics, Drug Resistance, Multiple, Bacterial, Genetic mutation, Infections, Inhibitor drugs, Lethal dose, Ligands, Medical sciences, Methicillin Resistance, Mice, Microbial Sensitivity Tests, Models, Molecular, Molecular Sequence Data, Mutation, Pharmacology, Pharmacology. Drug treatments, Polymerization, Protein Conformation, Pyridines - chemistry, Pyridines - metabolism, Pyridines - pharmacology, Pyridines - therapeutic use, Staphylococcal Infections - drug therapy, Staphylococcus aureus, Staphylococcus aureus - chemistry, Staphylococcus aureus - drug effects, Staphylococcus infections, Thiazoles - chemistry, Thiazoles - metabolism, Thiazoles - pharmacology, Thiazoles - therapeutic use, Tubulin - chemistry, Tubulin - metabolism