Antibiotic adjuvants have no or little antibiotic activity themselves but can enhance the activity of co-administered antibiotics, or reverse antibiotic resistance mechanisms. Now, Song, Liu et al. report a broad-spectrum antibiotic adjuvant that reverses resistance in multi-drug resistant (MDR) Gram-negative pathogens. The short linear antibacterial peptide known as SLAP-S25 carries four non-natural amino acids of 2,4-diaminobutanoic acid and was found to increase the efficacy of antibiotics in all major classes. SLAP-S25 potentiated the efficacy of antibiotics against diverse Gram-negative bacteria, including carbapenem-resistant and colistin-resistant Escherichia coli, and reversed resistance to MDR E. coli in animal models. SLAP-S25 binds to lipopolysaccharide and phosphatidylglycerol to induce membrane damage, which is required for synergy with antibiotics.
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Song, M. & Liu, Y. et al. A broad-spectrum antibiotic adjuvant reverses multidrug-resistant Gram-negative pathogens. Nat. Microbiol. https://doi.org/10.1038/s41564-020-0723-z (2020)
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York, A. Finding a good combination. Nat Rev Microbiol 18, 363 (2020). https://doi.org/10.1038/s41579-020-0392-1
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DOI: https://doi.org/10.1038/s41579-020-0392-1