In the battle against multidrug-resistant bacterial infections, an unexpected ally may have emerged.
A recent peer-reviewed study, published in the open-access journal PLOS Biology, reveals that an old antibiotic called nourseothricin could offer new hope in the fight against difficult and potentially deadly infections. The research, led by Harvard Medical School’s James Kirby and his team, highlights the promise of this natural compound.
Nourseothricin is derived from a soil fungus and consists of various forms of a complex molecule known as streptothricin.
Its discovery in the 1940s first raised hopes of its effectiveness against Gram-negative bacteria, known for their resilient outer protective layers that make them resistant to many antibiotics. However, the antibiotic’s toxicity to the kidneys halted its development.
Nevertheless, the increase in antibiotic-resistant bacterial infections has prompted scientists to revisit nourseothricin.
Revisiting Nourseothricin
Early investigations of nourseothricin faced challenges due to incomplete purification of streptothricins. However, recent research has demonstrated that different forms of streptothricin exhibit varying toxicities.
Particular interest in streptothricin-F, which has been shown to be less toxic while maintaining high activity against contemporary multidrug-resistant pathogens.
The researchers sought to characterize the antibacterial action, the renal toxicity and the mechanism of action of the purified forms of two streptothricins: D and F.
Streptothricin-D showed greater potency against drug-resistant Enterobacteriaceae and other bacterial species, but demonstrated renal toxicity at lower doses. Both forms exhibited high selectivity for Gram-negative bacteria.
Using cryo-electron microscopy, the researchers unveiled the extensive binding of streptothricin-F to a bacterial subunit of the ribosome. This interaction explained the translation errors induced by these antibiotics in their target bacteria. Interestingly, the binding mechanism differed from other known translation inhibitors, suggesting potential use when conventional agents prove ineffective.
Kirby expressed optimism about the unique and promising activity of the streptothricin scaffold. He highlighted the need for further preclinical exploration to determine its potential as a therapeutic option against multidrug-resistant Gram-negative pathogens.
“Isolated in 1942, streptothricin was the first antibiotic discovered with potent gram-negative activity,” Kirby said. “We find that not only is its activity potent, but it is highly active against the most resistant contemporary multidrug-resistant pathogens and acts through a unique mechanism to inhibit protein synthesis.”
The re-emergence of nourseothricin as a potent antibiotic marks an important development in the fight against multidrug-resistant infections. Although further research is needed to advance its clinical potential, the results offer a ray of hope in addressing the pressing challenge posed by antibiotic resistance.