The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
Beta-Lactam Antibiotics Induce a Lethal Malfunctioning of the Bacterial Cell Wall Synthesis Machinery
Open accessAbstract
SUMMARY Penicillin and related beta-lactams comprise one of our oldest and most widely used antibiotic therapies. These drugs have long been known to target enzymes called penicillin-binding proteins (PBPs) that build the bacterial cell wall. Investigating the downstream consequences of target inhibition and how they contribute to the lethal action of these important drugs, we demonstrate that beta-lactams do more than just inhibit the PBPs as is commonly believed. Rather, they induce a toxic malfunctioning of their target biosynthetic machinery involving a futile cycle of cell wall synthesis and degradation, thereby depleting cellular resources and bolstering their killing activity. Characterization of this mode of action additionally revealed a quality-control function for enzymes that cleave bonds in the cell wall matrix. The results thus provide insight into the mechanism of cell wall assembly and suggest how best to interfere with the process for future antibiotic development.
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Cites
Tipper, D. J., & Strominger, J. L. (1965) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.54.4.1133 · Cited by 1,008 · cited 1×
“Beta-lactams disrupt PG biogenesis by inactivating enzymes called penicillin-binding proteins (PBPs) (Tipper and Strominger, 1965).”
BackgroundHeidrich, C., Ursinus, A., Berger, J., Schwarz, H., & Höltje, J.-V. (2002) · Journal of Bacteriology · doi:10.1128/jb.184.22.6093-6099.2002 · Cited by 272
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ATP-Dependent Persister Formation in Escherichia coli
Shan, Y., Brown Gandt, A., Rowe, S. E., Deisinger, J. P., Conlon, B. P., & Lewis, K. (2017) · mBio · doi:10.1128/mbio.02267-16 · Cited by 508
Halawa, E. M., Fadel, M., Al-Rabia, M. W., Behairy, A., Nouh, N. A., Abdo, M., Olga, R., Fericean, L., Atwa, A. M., El-Nablaway, M., et al. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1305294 · Cited by 280
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Nie, X., Gao, F., You, W., Chen, G., Shao, Q., Wang, L.-H., Huang, W.-Q., Xia, L., Zhang, Z., Hong, C.-Y., et al. (2022) · Chemical Engineering Journal · doi:10.1016/j.cej.2022.138373 · Cited by 6
Metadata
- Authors
- Cho, H., Uehara, T., & Bernhardt, T. G.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2014-12
- Volume
- 159
- Issue
- 6
- Pages
- 1300-1311
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2037731504
- Cited by
- 642
- References
- 2
- FWCI
- 18.23
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Cho, H., Uehara, T., & Bernhardt, T. G. (2014). Beta-Lactam Antibiotics Induce a Lethal Malfunctioning of the Bacterial Cell Wall Synthesis Machinery. Cell. https://doi.org/10.1016/j.cell.2014.11.017
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