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CryoEM guided development of antibiotics for drug-resistant bacteria.
ChemMedChem 2019 January 23
While the ribosome is a common target for antibiotics challenges with crystallography can impede the development of new bioactives using structure based drug design approaches. Herein we exploit common structural features present in linezolid-resistant forms of both methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) to redesign the antibiotic. Enabled by rapid and facile cryoEM structures this process has identified LZD-5 and LZD-6, which inhibit the ribosomal function and growth of linezolid-resistant MRSA and VRE. The strategy discussed highlights the potential for cryoEM to facilitate the development of novel bioactive materials.
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