Endogenous Enzymes Enable Antimicrobial Activity
| Autor: | Miguel A. Aguilar Ramos, Ronald T. Raines, Kenton J. Hetrick |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
medicine.drug_class Antibiotics Mycobacterium smegmatis Drug Evaluation Preclinical Heterologous medicine.disease_cause 01 natural sciences Biochemistry Esterase Article 03 medical and health sciences Structure-Activity Relationship Anti-Infective Agents Drug Resistance Multiple Bacterial medicine Escherichia coli Prodrugs chemistry.chemical_classification biology 010405 organic chemistry Esterases Esters General Medicine Prodrug Antimicrobial biology.organism_classification 0104 chemical sciences 030104 developmental biology Enzyme chemistry Acrylates Molecular Medicine Bacteria Bacillus subtilis |
| Zdroj: | ACS Chem Biol |
| Popis: | In light of the continued threat of antimicrobial-resistant bacteria, new strategies to expand the repertoire of antimicrobial compounds are necessary. Prodrugs are an underexploited strategy in this effort. Here, we report on the enhanced antimicrobial activity of a prodrug toward bacteria having an enzyme capable of its activation. A screen led us to the sulfurol ester of the antibiotic trans-3-(4-chlorobenzoyl)acrylic acid. An endogenous esterase makes Mycolycibacterium smegmatis sensitive to this prodrug. Candidate esterases were identified, and their heterologous production made Escherichia coli sensitive to the ester prodrug. Taken together, these data suggest a new approach to the development of antimicrobial compounds that takes advantage of endogenous enzymatic activities to target specific bacteria. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|