The DOI matches its Crossref record; 202 of the 202 references it cites were found in a registry or an index.
β-Lactamases and β-Lactamase Inhibitors in the 21st Century
Open accessAbstract
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.
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Cites
Global increase and geographic convergence in antibiotic consumption between 2000 and 2015
Klein, E. Y., Van Boeckel, T. P., Martinez, E. M., Pant, S., Gandra, S., Levin, S. A., Goossens, H., & Laxminarayan, R. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1717295115 · Cited by 3,232
Kumarasamy, K. K., Toleman, M. A., Walsh, T. R., Bagaria, J., Butt, F., Balakrishnan, R., Chaudhary, U., Doumith, M., Giske, C. G., Irfan, S., et al. (2010) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(10)70143-2 · Cited by 2,922
Mobile Genetic Elements Associated with Antimicrobial Resistance
Partridge, S. R., Kwong, S. M., Firth, N., & Jensen, S. O. (2018) · Clinical Microbiology Reviews · doi:10.1128/cmr.00088-17 · Cited by 2,751
A functional classification scheme for beta-lactamases and its correlation with molecular structure
Bush, K., Jacoby, G. A., & Medeiros, A. A. (1995) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.39.6.1211 · Cited by 2,475
Jacoby, G. A. (2009) · Clinical Microbiology Reviews · doi:10.1128/cmr.00036-08 · Cited by 2,165
Ambler, R. P. (1980) · Philosophical Transactions of the Royal Society of London. B, Biological Sciences · doi:10.1098/rstb.1980.0049 · Cited by 1,823
Three Decades of β-Lactamase Inhibitors
Drawz, S. M., & Bonomo, R. A. (2010) · Clinical Microbiology Reviews · doi:10.1128/cmr.00037-09 · Cited by 1,709
Fleming, A. (1929) · PubMed Central · Cited by 1,647
Yigit, H., Queenan, A. M., Anderson, G. J., Domenech-Sanchez, A., Biddle, J. W., Steward, C. D., Alberti, S., Bush, K., & Tenover, F. C. (2001) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.45.4.1151-1161.2001 · Cited by 1,639
Logan, L. K., & Weinstein, R. A. (2017) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiw282 · Cited by 1,584
Cited by
Molecular mechanisms of antibiotic resistance revisited
Darby, E. M., Trampari, E., Siasat, P., Gaya, M. S., Alav, I., Webber, M. A., & Blair, J. M. A. (2023) · Nature Reviews Microbiology · doi:10.1038/s41579-022-00820-y · Cited by 1,398
Epidemiology of β-Lactamase-Producing Pathogens
Bush, K., & Bradford, P. A. (2020) · Clinical Microbiology Reviews · doi:10.1128/cmr.00047-19 · Cited by 938
Acinetobacter baumannii Antibiotic Resistance Mechanisms
Kyriakidis, I., Vasileiou, E., Pana, Z. D., & Tragiannidis, A. (2021) · Pathogens · doi:10.3390/pathogens10030373 · Cited by 678
Progress in Alternative Strategies to Combat Antimicrobial Resistance: Focus on Antibiotics
Murugaiyan, J., Kumar, P. A., Rao, G. S., Iskandar, K., Hawser, S., Hays, J. P., Mohsen, Y., Adukkadukkam, S., Awuah, W. A., Jose, R. A. M., et al. (2022) · Antibiotics · doi:10.3390/antibiotics11020200 · Cited by 567
Exploring phytochemicals for combating antibiotic resistance in microbial pathogens
Khare, T., Anand, U., Dey, A., Assaraf, Y. G., Chen, Z.-S., Liu, Z., & Kumar, V. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.720726 · Cited by 281
Metadata
- Authors
- Tooke, C. L., Hinchliffe, P., Bragginton, E. C., Colenso, C. K., Hirvonen, V. H. A., Takebayashi, Y., & Spencer, J.
- Venue
- Journal of Molecular Biology
- Publisher
- Elsevier BV
- Published
- 2019-08
- Volume
- 431
- Issue
- 18
- Pages
- 3472-3500
- ISSN
- 0022-2836 (ISSN-L)
- OpenAlex
- W2925800094
- Cited by
- 1,016
- References
- 202
- FWCI
- 27.30
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Tooke, C. L., Hinchliffe, P., Bragginton, E. C., Colenso, C. K., Hirvonen, V. H. A., 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
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