Darobactin - Novel Antibiotic Against Drug-resistant Bacteria

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What is darobactin a?

Darobactin A has an unusual fold and is a 7mer peptide with two fused rings that produce a rigid, preformed β-strand. Darobactin forms a β-β interaction with the lateral gate of BamA, outcompeting native substrates 15. Computational approaches comprise another important area of antibiotic discovery.

Can darobactin be used as an antibiotic?

Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Darobactin is an experimental antibiotic compound that may be effective against Gram-negative bacteria. If it can be developed into a human-compatible form it would be the first to come from an animal microbiome.

Is darobactin a Gram-negative pathogen?

In this context, Gram-negative pathogens listed in the WHO priority list are particularly problematic. Darobactin is a ribosomally produced and post-translationally modified bicyclic heptapeptide antibiotic selectively killing Gram-negative bacteria by targeting the outer membrane protein BamA.

How is darobactin coded?

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.

How does darobactin work?

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.

How are darobactin-producing organisms identified?

The proposed darobactin-producing organisms were identified by a BLASTp search of the seven-amino-acid sequence of darobactin A, confirming the presence of darBCDE downstream of the propeptide. Amino acid changes from darobactin A are highlighted in red. f, The propeptide sequence of the various darobactin analogues.

What Is Darobactin

1. https://en.wikipedia.org/wiki/Darobactin
2. https://www.nature.com/articles/s41586-019-1791-1
3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7188312/
4. https://pubmed.ncbi.nlm.nih.gov/34659729/
5. https://pubs.acs.org/doi/10.1021/acs.jmedchem.3c01660
6. https://pubs.rsc.org/en/content/articlehtml/2021/sc/d1sc02725e