Pghi-4 restored vancomycin’s bacteria-killing activity in drug-resistant E. faecium when researchers paired the small molecule with the antibiotic in a new CSHL-Scripps study.
SagA, a bacterial enzyme tied to resistance, was the key target: inhibiting it made the pathogen more susceptible to vancomycin rather than requiring an entirely new antibiotic.
More than 150 compounds in a molecular library built with CSHL’s diversity oriented clicking method enabled the finding; pghi-4 itself was first identified in the Moses lab in 2020.
The work, published in Nature Communications on June 16, points to antibiotic adjuvants as a broader strategy for reviving existing drugs against other resistant pathogens, potentially including tuberculosis.
A revived antibiotic can now kill superbugs. Is this the key to ending the resistance crisis?
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SagA Inhibition Revives Vancomycin Potency Against Deadly VREfm Superbugs
Overview
Vancomycin-Resistant Enterococcus faecium (VREfm) is a major cause of healthcare-associated infections and represents a growing crisis in global health due to its resistance to antibiotics. This resistance leads to significant economic burdens, with costs predicted to reach hundreds of billions of dollars annually. The report highlights a novel strategy that targets a key bacterial enzyme, SagA, to restore the effectiveness of vancomycin against VREfm. By focusing on this innovative approach, researchers aim to overcome the challenges posed by multidrug-resistant pathogens and reduce the impact of antimicrobial resistance on healthcare systems worldwide.