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A new antibiotic kills pathogens without detectable resistance
Open accessAbstract
Antibiotic resistance is spreading faster than the introduction of new compounds into clinical practice, causing a public health crisis. Most antibiotics were produced by screening soil microorganisms, but this limited resource of cultivable bacteria was overmined by the 1960s. Synthetic approaches to produce antibiotics have been unable to replace this platform. Uncultured bacteria make up approximately 99% of all species in external environments, and are an untapped source of new antibiotics. We developed several methods to grow uncultured organisms by cultivation in situ or by using specific growth factors. Here we report a new antibiotic that we term teixobactin, discovered in a screen of uncultured bacteria. Teixobactin inhibits cell wall synthesis by binding to a highly conserved motif of lipid II (precursor of peptidoglycan) and lipid III (precursor of cell wall teichoic acid). We did not obtain any mutants of Staphylococcus aureus or Mycobacterium tuberculosis resistant to teixobactin. The properties of this compound suggest a path towards developing antibiotics that are likely to avoid development of resistance.
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Cites
Drugs for bad bugs: confronting the challenges of antibacterial discovery
Payne, D. J., Gwynn, M. N., Holmes, D. J., & Pompliano, D. L. (2007) · Nature Reviews Drug Discovery · doi:10.1038/nrd2201 · Cited by 2,512
Cited by
Antimicrobial resistance: a global multifaceted phenomenon
Prestinaci, F., Pezzotti, P., & Pantosti, A. (2015) · Pathogens and Global Health · doi:10.1179/2047773215y.0000000030 · Cited by 3,296
Byrd, A. L., Belkaid, Y., & Segre, J. A. (2018) · Nature Reviews Microbiology · doi:10.1038/nrmicro.2017.157 · Cited by 2,806
Antibiotics: past, present and future
Hutchings, M. I., Truman, A. W., & Wilkinson, B. (2019) · Current Opinion in Microbiology · doi:10.1016/j.mib.2019.10.008 · Cited by 2,370
Therapeutic peptides: Historical perspectives, current development trends, and future directions
Lau, J. L., & Dunn, M. K. (2018) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2017.06.052 · Cited by 1,879
Human commensals producing a novel antibiotic impair pathogen colonization
Zipperer, A., Konnerth, M. C., Laux, C., Berscheid, A., Janek, D., Weidenmaier, C., Burian, M., Schilling, N. A., Slavetinsky, C., Marschal, M., et al. (2016) · Nature · doi:10.1038/nature18634 · Cited by 938
Metadata
- Authors
- Ling, L. L., Schneider, T., Peoples, A. J., Spoering, A. L., Engels, I., Conlon, B. P., Mueller, A., Schäberle, T. F., Hughes, D. E., Epstein, S., Jones, M., Lazarides, L., Steadman, V. A., Cohen, D. R., Felix, C. R., Fetterman, K. A., Millett, W. P., Nitti, A. G., Zullo, A. M., Chen, C., & Lewis, K.
- Venue
- Nature
- Published
- 2015-01-07
- Volume
- 517
- Issue
- 7535
- Pages
- 455-459
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2012251902
- Cited by
- 2,428
- References
- 1
- FWCI
- 206.21
- Type
- journal article
- Language
- en
- Open access
- green
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- The paper
- Ling, L. L., Schneider, T., Peoples, A. J., Spoering, A. L., Engels, I., Conlon, B. P., Mueller, A., Schäberle, T. F., Hughes, D. E., Epstein, S., Jones, M., Lazarides, L., Steadman, V. A., Cohen, D. R., Felix, C. R., Fetterman, K. A., Millett, W. P., Nitti, A. G., Zullo, A. M., . . . Lewis, K. (2015). A new antibiotic kills pathogens without detectable resistance. Nature. https://doi.org/10.1038/nature14098
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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