An unexpected ally may emerge in the fight against multidrug-resistant bacterial infections.

A recent peer-reviewed study, Published in an open access journal PLOS Biology, shows that an old antibiotic called norseothricin offers new hope in fighting challenging and life-threatening infections. Research led by James Kirby and his team from Harvard Medical School highlights the promise of this natural compound.

Nourseothricin is derived from a soil fungus and consists of complex molecules known as streptothricin.

In the year The discovery in the 1940s first raised the prospect of effectiveness against gram-negative bacteria, famous for their outer protective membranes resistant to many antibiotics. However, antibiotics stopped the development of kidney poisoning.

However, the rise of antibiotic-resistant bacterial infections has prompted scientists to revisit nurseothricin.

Antibiotics (illustrative) (Credit: FLICKR)

Revisiting Nourseothricin

Early investigations on norseothricin encountered challenges due to the complete clearance of streptothricin. However, recent studies have shown that streptothricin has different toxic substances.

Special interest in streptothricin-F, which is less toxic while retaining high activity against modern drug-resistant pathogens.

The researchers aimed to identify the antibacterial action, renal toxicity and the mechanism of action of two streptothricins: D and F.

Streptothricin-D showed greater potency against drug-resistant Enterobacterales and other bacterial species but showed less renal toxicity. Both forms showed high selectivity for Gram-negative bacteria.

The researchers used cryo-electron microscopy to reveal the binding of streptothricin F to a subunit of the bacterial ribosome. This interaction explained the translational errors these antibiotics induced in their target bacteria. Interestingly, its binding mechanism is different from other known translation inhibitors, suggesting that it may be used when conventional agents prove ineffective.

Kirby expressed his hopes for the unique and promising activity of the streptothricin scaffold. They stress that further preclinical exploration is needed to identify drug-resistant Gram-negative pathogens as a treatment option.

“Isolated in 1942, streptothricin was the first antibiotic with potent gram-negative activity,” Kirby said. “We note that the activity is not only powerful, but also very active, very strong modern drug resistant pathogens and works in a unique way to inhibit protein synthesis.”

Nourseothricin’s indications as a potent antibiotic and an important advance in the fight against multidrug-resistant infections. While more research is needed to advance its clinical potential, the findings offer promising solutions to the challenges of antibiotic resistance.

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