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Cited by 743

The DOI matches its Crossref record; 59 of the 59 references it cites were found in a registry or an index.

A new antibiotic selectively kills Gram-negative pathogens

Open access
Imai, Yu, Meyer, Kirsten J., Iinishi, Akira, Favre-Godal, Quentin, Green, Robert, Manuse, Sylvie, Caboni, Mariaelena, Mori, Miho, Niles, Samantha, Ghiglieri, Meghan, Honrao, Chandrashekhar, Ma, Xiaoyu, Guo, Jason J., Makriyannis, Alexandros, Linares-Otoya, Luis, Böhringer, Nils, Wuisan, Zerlina G., Kaur, Hundeep, Wu, Runrun, Mateus, André, Typas, Athanasios, Savitski, Mikhail M., Espinoza, Josh L., O’Rourke, Aubrie, Nelson, Karen E., Hiller, Sebastian, Noinaj, Nicholas, Schäberle, Till F., D’Onofrio, Anthony, Lewis, Kim·2019·Nature
DOI 10.1038/s41586-019-1791-1
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Abstract

The current need for novel antibiotics is especially acute for drug-resistant Gram-negative pathogens1,2. These microorganisms have a highly restrictive permeability barrier, which limits the penetration of most compounds3,4. As a result, the last class of antibiotics that acted against Gram-negative bacteria was developed in the 1960s2. We reason that useful compounds can be found in bacteria that share similar requirements for antibiotics with humans, and focus on Photorhabdus symbionts of entomopathogenic nematode microbiomes. Here we report a new antibiotic that we name darobactin, which was obtained using a screen of Photorhabdus isolates. Darobactin is coded by a silent operon with little production under laboratory conditions, and is ribosomally synthesized. Darobactin has an unusual structure with two fused rings that form post-translationally. The compound is active against important Gram-negative pathogens both in vitro and in animal models of infection. Mutants that are resistant to darobactin map to BamA, an essential chaperone and translocator that folds outer membrane proteins. Our study suggests that bacterial symbionts of animals contain antibiotics that are particularly suitable for development into therapeutics. Bacterial symbionts of animals may contain antibiotics that are particularly suitable for development into therapeutics; one such compound, darobactin, is active against important Gram-negative pathogens both in vitro and in animal models of infection.

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Metadata

Authors
Imai, Y., Meyer, K. J., Iinishi, A., Favre-Godal, Q., Green, R., Manuse, S., Caboni, M., Mori, M., Niles, S., Ghiglieri, M., Honrao, C., Ma, X., Guo, J. J., Makriyannis, A., Linares-Otoya, L., Böhringer, N., Wuisan, Z. G., Kaur, H., Wu, R., Mateus, A., Typas, A., Savitski, M. M., Espinoza, J. L., O’Rourke, A., Nelson, K. E., Hiller, S., Noinaj, N., Schäberle, T. F., D’Onofrio, A., & Lewis, K.
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2019-11-20
Volume
576
Issue
7787
Pages
459-464
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/s41586-019-1791-1
OpenAlex
W2989562929
Cited by
743
References
59
FWCI
41.51
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: A new antibiotic selectively kills Gram-negative pathogens. https://app.cochat.ai/papers/10.1038/s41586-019-1791-1
The paper
Imai, Y., Meyer, K. J., Iinishi, A., Favre-Godal, Q., Green, R., Manuse, S., Caboni, M., Mori, M., Niles, S., Ghiglieri, M., Honrao, C., Ma, X., Guo, J. J., Makriyannis, A., Linares-Otoya, L., Böhringer, N., Wuisan, Z. G., Kaur, H., Wu, R., . . . Lewis, K. (2019). A new antibiotic selectively kills Gram-negative pathogens. Nature. https://doi.org/10.1038/s41586-019-1791-1

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.