Key points
- Researchers developed a compound that may restore the effectiveness of streptogramin antibiotics.
- Powerful X-rays at synchrotron facilities were used to study molecular interactions.
- The compound inhibits a bacterial enzyme (VatD) that renders streptogramins ineffective.
- The study identifies a promising lead for new therapies against antibiotic-resistant bacteria.
The rise of antibiotic-resistant bacteria poses a significant threat to global health. While Alexander Fleming’s discovery of penicillin revolutionized medicine, bacteria have continually adapted, rendering many antibiotics obsolete. A recent breakthrough, however, offers a potential solution.
A team at the University of California, San Francisco, led by Professor James Fraser, has developed a novel compound that could revitalize the efficacy of streptogramins, a class of antibiotics effective against multidrug-resistant Gram-positive bacteria. These bacteria often cause serious infections such as blood poisoning and severe skin infections.
The research leveraged the power of X-ray crystallography at the Stanford Synchrotron Radiation Lightsource (SSRL) and the Advanced Light Source (ALS) at the Lawrence Berkeley National Laboratory. By studying the molecular structures and interactions between candidate compounds and bacteria at an atomic level, researchers identified binding sites previously unknown.
These sites are crucial for the activity of Virginiamycin acetyl transferase D (VatD), a bacterial enzyme that neutralizes streptogramins. The newly developed compound successfully interferes with VatD’s function, thereby restoring the antibiotic’s ability to combat bacteria that have become resistant.
Postdoctoral researcher Pooja Asthana, lead author of the study published in Structure, meticulously screened hundreds of small molecules. Using X-ray crystallography, she identified over 30 fragments that bound to VatD.
Further modifications resulted in a compound demonstrating moderate activity against VatD, proving the concept and paving the way for future optimization. The findings represent a significant step forward in addressing the urgent global challenge of antibiotic resistance.
This exciting discovery highlights the potential of utilizing advanced technologies, such as synchrotron X-rays, to accelerate the development of new antimicrobial therapies. The research team will continue to refine the compound’s structure, aiming to enhance its inhibitory properties significantly.
Successful future development could lead to the widespread reintroduction of streptogramins, offering a much-needed weapon in the fight against drug-resistant infections in both clinical and agricultural settings.
