An unexpected ally may have appeared in the fight against multidrug-resistant bacterial infections.
In a recent peer-reviewed study, Published in an open access journal PLOS biology, reveals that an old antibiotic called nurseothricin may offer new hope in fighting difficult and potentially life-threatening infections. The study, led by James Kirby and his team at Harvard Medical School, highlights the promise of this natural compound.
Nurseothricin is derived from soil fungi and is composed of various forms of complex molecules known as streptothricins.
Its discovery in the 1940s initially raised hopes for its efficacy against Gram-negative bacteria. Gram-negative bacteria are notorious for their elastic outer protective layer that confers resistance to many antibiotics. However, its development was discontinued due to the toxicity of the antibiotic to the kidney.
Nevertheless, the increase in antibiotic-resistant bacterial infections has caused scientists to reconsider nurseothricin.
Rethinking Nurseothricin
Early studies of nurseothricin were challenged by incomplete purification of streptothricin. However, recent studies have demonstrated that substances different from streptothricin exhibit varying toxicities.
Of particular interest is Streptothricin F, which has demonstrated low toxicity while maintaining high activity against modern multidrug-resistant pathogens.
The researchers aimed to characterize the antibacterial activity, nephrotoxicity, and mechanism of action of two purified streptothricins D and F.
Streptothricin-D showed higher potency against drug-resistant enterobacterial species and other bacterial species, but nephrotoxicity at lower doses. Both forms showed high selectivity against Gram-negative bacteria.
Using cryogenic electron microscopy, the researchers revealed that streptothricin-F is extensively bound to bacterial ribosomal subunits. This interaction explains the translational errors induced within the target bacteria by these antibiotics. Interestingly, its binding mechanism is distinct from other known translation inhibitors, suggesting its potential use when conventional agents prove ineffective.
Kirby expressed optimism about the unique and promising activity of the streptothricin scaffold. He emphasized the need for further preclinical investigations to determine its potential as a therapeutic option for multidrug-resistant Gram-negative pathogens.
“Streptothricin, isolated in 1942, was the first antibiotic discovered to have potent Gram-negative activity,” Kirby said. “We found that it is not only potent, but highly active against some of the most potent multidrug-resistant pathogens of our time, and that it works by a unique mechanism of inhibiting protein synthesis. ”
The re-emergence of nurseothricin as a potent antibiotic represents an important advance in the fight against multidrug-resistant infections. Although additional research is needed to increase its clinical potential, this discovery offers a glimmer of hope in addressing the pressing challenges posed by antibiotic resistance.
