Antibacterial Spectrum of a Tetrazole-Based Reversible Inhibitor of Serine β-Lactamases
| Autor: | Pemberton, Orville, Zhang, Xiujun, Nichols, Derek, DeFrees, Kyle, Jaishankar, Priyadarshini, Bonnet, Richard, Adams, Adam, Shaw, Lindsey, Renslo, Adam, Chen, Yu, Adams, Jessie |
|---|---|
| Přispěvatelé: | Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), NIH AI103158, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte - Clermont Auvergne (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne) |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
030106 microbiology Mutant Tetrazoles Microbial Sensitivity Tests Microbiology beta-Lactamases Serine 03 medical and health sciences chemistry.chemical_compound Mechanisms of Resistance Gram-Negative Bacteria polycyclic compounds Pharmacology (medical) Tetrazole Pharmacology biology Chemistry β lactamases [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology Pharmacology and Pharmaceutical Sciences biochemical phenomena metabolism and nutrition biology.organism_classification bacterial infections and mycoses β-lactamase [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology In vitro Anti-Bacterial Agents inhibitor antibacterial 030104 developmental biology Infectious Diseases Biochemistry 5.1 Pharmaceuticals Medical Microbiology Development of treatments and therapeutic interventions Bacteria |
| Zdroj: | Antimicrobial Agents and Chemotherapy Antimicrobial Agents and Chemotherapy, American Society for Microbiology, 2018, 62 (8), ⟨10.1128/AAC.02563-17⟩ Antimicrobial agents and chemotherapy, vol 62, iss 8 |
| ISSN: | 0066-4804 1098-6596 |
| Popis: | International audience; CTX-M is the most prevalent family of extended-spectrum β-lactamases. We recently developed a tetrazole-derived noncovalent inhibitor of CTX-M-9. Here, we present the biochemical and microbiological activity of this inhibitor across a representative panel of serine β-lactamases and Gram-negative bacteria. The compound displayed significant activity against all major subgroups of CTX-M, including CTX-M-15, while it exhibited some low-level inhibition of other serine β-lactamases. Complex crystal structures with the CTX-M-14 S237A mutant and CTX-M-27 illustrate the binding contribution of specific active-site residues on the β3 strand. In vitro pharmacokinetic studies revealed drug-like properties and positive prospects for further optimization. These studies suggest that tetrazole-based compounds can provide novel chemotypes for future serine β-lactamase inhibitor discovery. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|