Neglected 80-year-old antibiotic is effective against multi-drug resistant bacteria

A recent study published in the journal PLOS Biology suggests that an old antibiotic could be a valuable weapon against drug-resistant bacterial infections. The research, conducted by James Kirby and his team from Harvard Medical School, explores the potential of an antibiotic called nourseothricin, which was discovered in the 1940s but was abandoned due to kidney toxicity.

Nourseothricin is derived from a soil fungus and contains multiple forms of a complex molecule known as streptothricin. Gram-negative bacteria, which have a tough outer protective layer, are particularly difficult to treat with common antibiotics. Previous studies on nourseothricin were limited due to incomplete purification of the streptothricins. However, recent research has revealed that one of its forms, streptothricin-F, is significantly less toxic to kidneys while still showing high activity against drug-resistant bacteria.

In their study, the researchers investigated the antibacterial action, renal toxicity, and mechanism of action of highly purified forms of two streptothricins, D and F. They found that the D form was more potent against drug-resistant bacteria, but also caused renal toxicity at a lower dose. Both forms displayed a strong preference for Gram-negative bacteria.

Using cryo-electron microscopy, the researchers discovered that streptothricin-F, one of the forms of nourseothricin, binds extensively to a specific part of the bacterial ribosome. This binding mechanism leads to translation errors in the bacteria, which is known to be caused by these types of antibiotics. What is interesting is that the binding interaction of streptothricin-F is different from other known translation inhibitors, suggesting it could be useful when those other agents are not effective.

Based on the unique and promising activity of streptothricin-F, lead researcher James Kirby stated that the streptothricin scaffold should be further investigated in pre-clinical studies as a potential treatment for multidrug-resistant Gram-negative pathogens. He also mentioned that streptothricin, isolated in 1942, was the first antibiotic to demonstrate potent activity against gram-negative bacteria. The research team found that not only is streptothricin highly potent, but it also effectively targets contemporary multidrug-resistant pathogens and operates through a unique mechanism of inhibiting protein synthesis.