2. Academic Validation
  3. A Family of Antibiotics That Evades Resistance by Binding Polyprenyl Phosphates

A Family of Antibiotics That Evades Resistance by Binding Polyprenyl Phosphates

  • ACS Infect Dis. 2023 Dec 8;9(12):2394-2400. doi: 10.1021/acsinfecdis.3c00475.
Adam F Rosenzweig 1,  Zongqiang Wang 1,  Adrián Morales-Amador 1,  Kaylyn Spotton 1,  Sean F Brady 1
Affiliations

Affiliation

  • 1 Laboratory of Genetically Encoded Small Molecules, The Rockefeller University, 1230 York Avenue, New York, New York 10065, United States.
PMID: 37937847 DOI: 10.1021/acsinfecdis.3c00475
Abstract

Cilagicin is a Gram-positive active Antibiotic that has a dual polyprenyl phosphate binding mechanism that impedes resistance development. Here we bioinformatically screened predicted non-ribosomal polypeptide synthetase encoded structures to search for Antibiotics that might similarly avoid resistance development. Synthesis and bioactivity screening of the predicted structures that we identified led to three Antibiotics that are active against multidrug-resistant Gram-positive pathogens, two of which, paenilagicin and virgilagicin, did not lead to resistance even after prolonged Antibiotic exposure.

Keywords

antibiotics; cilagicin; no resistance; polyprenyl phosphate; synthetic bioinformatic natural product.

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