β-Lactamases and β-Lactamase Inhibitors in the 21st Century
| Autor: | James Spencer, Catherine L. Tooke, Philip Hinchliffe, Yuiko Takebayashi, Viivi H. A. Hirvonen, Charlotte K. Colenso, Eilis C. Bragginton |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
β-lactam
QM/MM quantum mechanics/molecular mechanics TEM Temoneira (β-lactamase) medicine.disease_cause OXA oxacillinase Serine carbapenemase 0302 clinical medicine Structural Biology Catalytic Domain polycyclic compounds chemistry.chemical_classification 0303 health sciences SBL serine β-lactamase Enterobacteriaceae 3. Good health Anti-Bacterial Agents NDM New Delhi metallo-β-lactamase Drug Combinations DBO diazabicyclooctane beta-Lactamase Inhibitors CTX-M cefotaximase metallo-β-lactamase PBP penicillin-binding protein Computational biology Biology beta-Lactams Article beta-Lactamases 03 medical and health sciences Antibiotic resistance Drug Resistance Bacterial Gram-Negative Bacteria medicine Humans enzyme mechanism antimicrobial resistance Molecular Biology Escherichia coli MBL metallo-β-lactamase 030304 developmental biology Pseudomonas aeruginosa SFX serial femtosecond crystallography biochemical phenomena metabolism and nutrition biology.organism_classification Interspersed Repetitive Sequences Enzyme VIM Verona imipenemase Carbapenem-Resistant Enterobacteriaceae chemistry SHV sulfydryl variant Carbapenems ESBL extended spectrum β-lactamase KPC Klebsiella pneumoniae carbapenemase Mobile genetic elements 030217 neurology & neurosurgery Bacteria |
| Zdroj: | Journal of Molecular Biology Tooke, C, Hinchliffe, P, Bragginton, E, Colenso, C K, Hirvonen, V, Takebayashi, Y & Spencer, J 2019, ' β-Lactamases and β-Lactamase Inhibitors in the 21st Century ', Journal of Molecular Biology . https://doi.org/10.1016/j.jmb.2019.04.002 |
| ISSN: | 1089-8638 0022-2836 |
| Popis: | The β-lactams retain a central place in the antibacterial armamentarium. In Gram-negative bacteria, β-lactamase enzymes that hydrolyze the amide bond of the four-membered β-lactam ring are the primary resistance mechanism, with multiple enzymes disseminating on mobile genetic elements across opportunistic pathogens such as Enterobacteriaceae (e.g., Escherichia coli) and non-fermenting organisms (e.g., Pseudomonas aeruginosa). β-Lactamases divide into four classes; the active-site serine β-lactamases (classes A, C and D) and the zinc-dependent or metallo-β-lactamases (MBLs; class B). Here we review recent advances in mechanistic understanding of each class, focusing upon how growing numbers of crystal structures, in particular for β-lactam complexes, and methods such as neutron diffraction and molecular simulations, have improved understanding of the biochemistry of β-lactam breakdown. A second focus is β-lactamase interactions with carbapenems, as carbapenem-resistant bacteria are of grave clinical concern and carbapenem-hydrolyzing enzymes such as KPC (class A) NDM (class B) and OXA-48 (class D) are proliferating worldwide. An overview is provided of the changing landscape of β-lactamase inhibitors, exemplified by the introduction to the clinic of combinations of β-lactams with diazabicyclooctanone and cyclic boronate serine β-lactamase inhibitors, and of progress and strategies toward clinically useful MBL inhibitors. Despite the long history of β-lactamase research, we contend that issues including continuing unresolved questions around mechanism; opportunities afforded by new technologies such as serial femtosecond crystallography; the need for new inhibitors, particularly for MBLs; the likely impact of new β-lactam:inhibitor combinations and the continuing clinical importance of β-lactams mean that this remains a rewarding research area. Graphical Abstract Unlabelled Image |
| Databáze: | OpenAIRE |
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