Rediscovered antibiotic shows potential against multidrug resistant infections - study

In the battle against multi-drug 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 combating challenging and potentially life-threatening infections. The research, led by James Kirby from Harvard Medical School 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 initially raised hopes of its efficacy against Gram-negative bacteria, notorious for their resilient outer protective layers that render them resistant to many antibiotics. However, the antibiotic's toxicity to kidneys halted its development. 

Nevertheless, the rise of antibiotic-resistant bacterial infections prompted scientists to revisit nourseothricin.

Revisiting nourseothricin

Early investigations into nourseothricin faced challenges due to incomplete purification of the streptothricins. Recent research, however, has demonstrated that different from of streptothricin exhibit varying toxicities.

Of particular interest in streptothricin-F, which proved less toxic while retaining high activity against contemporary multidrug-resistant pathogen. 

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

Streptothricin-D showcased greater potency against drug-resistant Enterobacterales and other bacterial species but demonstrated renal toxicity at lower doses. Both forms exhibited high selectivity for Gram-negative bacteria.

Through cryo-electron microscopy, the researchers unveiled the extensive binding of streptothricin-F to a bacterial ribosome subunit. 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 regarding the streptothricin scaffold's unique and promising activity. He emphasized the need for further pre-clinical 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 it activity potent, but that it is highly active the hardiest contemporary multidrug-resistant pathogens and works by a unique mechanism to inhibition protein synthesis."

The reemergence of nourseothricin as a potent antibiotic marks and important development in the fight against multidrug-resistant infections. While additional research is needed to advance its clinical potential, the findings offer a glimmer of hope in addressing the pressing challenge posed by antibiotic resistance.