Scientists have revived the powerful antibiotic vancomycin to fight drug-resistant superbugs. By pairing it with a small molecule called pghi-4, researchers from CSHL and Scripps Research were able to kill resistant E. faecium. The companion drug works by inhibiting a key bacterial enzyme, SagA, restoring vancomycin's effectiveness. This strategy could lead to new treatments for other resistant infections.
Antibiotic resistance threat
- ▪Antibiotic resistance is a serious danger to modern medicine, making common infections harder to treat
- ▪Antibiotic resistance increases risks associated with routine surgery, cancer care, and other medical procedures
- ▪Drug-resistant pathogens like MRSA and Clostridium difficile (C. diff) can spread through hospitals, nursing homes, and communities
Diversity oriented clicking technique
- ▪Using the DOC technique, researchers built a library containing more than 150 different compounds for drug discovery
- ▪Professor John Moses's team at Cold Spring Harbor Laboratory (CSHL) developed a chemical reaction technique called diversity oriented clicking (DOC)
Vancomycin restoration strategy
- ▪When drug-resistant E. faecium was treated with both vancomycin and the molecule pghi-4, the antibiotic regained its ability to kill the bacteria
- ▪Scientists restored the effectiveness of the antibiotic vancomycin by pairing it with a companion molecule, an approach using antibiotic adjuvants
- ▪Vancomycin is a powerful antibiotic commonly used against severe infections, including those caused by MRSA and Clostridium difficile (C. diff)
SagA enzyme inhibition
- ▪The new strategy targets and blocks a bacterial enzyme called secreted antigen A (SagA)
- ▪The SagA enzyme was blocked using a small molecule known as pghi-4, which was first discovered in 2020
Molecular library collaboration
- ▪The research was a collaboration between Professor John Moses's team at CSHL and Professor Howard Hang's team at Scripps Research
- ▪Researchers hope similar approaches using the molecular library could lead to treatments for other drug-resistant infections, including resistant forms of tuberculosis
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