A new antibiotic selectively kills Gram-negative pathogens
By Y. Imai, Kirsten J. Meyer, Akira Iinishi, Q. Favre-Godal, R. Green, S. Manuse, M. Caboni, Miho Mori, Samantha Niles, Meghan Ghiglieri and 20 more. Nature, 2019
606 citations recorded by the source corpus.
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.
Subfields: Insect Science
View Paper: https://www.semanticscholar.org/paper/6dffa1db89c7fac053184a341caa9385966ec501
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Citations in the corpus
- Discovery of a structural class of antibiotics with explainable deep learning (2023, background): “Antibiotic candidates have been discovered in the past decade through various approaches based on natural product mining 2,3 , high-throughput screening 4 , evolution and phylogeny analyses 5,6 , structure-guided and rational design 7,8 , and in silico screens using machine learning 1,12–14 .”
- Antibiotic resistance and persistence—Implications for human health and treatment perspectives (2020, positive): “They screened isolates of Photorhabdus , symbionts of entomopathogenic nematode microbiomes, for antimicrobial substances against Gram-negative bacteria and isolated a new compound named darobactin (Imai et al , 2019).”