β-Lactamases and β-Lactamase Inhibitors in the 21st Century
| العنوان: | β-Lactamases and β-Lactamase Inhibitors in the 21st Century |
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| المؤلفون: | James Spencer, Catherine L. Tooke, Philip Hinchliffe, Yuiko Takebayashi, Viivi H. A. Hirvonen, Charlotte K. Colenso, Eilis C. Bragginton |
| المصدر: | 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 |
| بيانات النشر: | Elsevier, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 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 |
| الوصف: | 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 |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1089-8638 0022-2836 |
| DOI: | 10.1016/j.jmb.2019.04.002 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fc19dc6247df2029d1d290c042b56f03 http://europepmc.org/articles/PMC6723624 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....fc19dc6247df2029d1d290c042b56f03 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10898638 00222836 |
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| DOI: | 10.1016/j.jmb.2019.04.002 |