An antibiotic developed around 80 years ago before being abandoned and forgotten could once again offer exciting new solutions, this time to the emerging threat of drug-resistant superbugs.
Half of the bacteria-killing drugs we use today are variants of compounds discovered nearly a century ago, during this “golden age” of antibiotics. One called streptothricin was isolated in the 1940s, drawing attention to its potential in treating infections caused by so-called gram-negative bacteria.
Unlike gram-positive bacteria, these microbes lack the robust cell wall that many antibiotics target. Finding alternatives has been one of the great challenges of the pharmaceutical industry. In 2017, the World Health Organization (WHO) published a list of the most dangerous and drug-resistant pathogens. Most were gram-negative bacteria.
But despite its potential to kill bacteria, streptothricin was unsuccessful. It was found to be too toxic to human kidney health in an early study and was later buried in scientific literature.
Harvard University pathologist James Kirby and his colleagues are digging into it, exploring its potential under a new name – nourseothricin.
“Now, with the emergence of multidrug-resistant pathogens, for which there are few or no active antibiotics available for treatment, it is time to revisit and explore the potential of what we have previously overlooked,” said Kirby told ScienceAlert.
Nourseothricin is a natural product made by Gram-positive soil bacteria. It is actually a mixture of antibiotics, with individual names such as streptothricin F (SF) and streptothricin D (SD).
While nourseothricin and SD show toxic effects on kidney cells in the laboratory, Kirby and his colleagues have now established that this is not the case for SF. This compound is still very effective at killing drug-resistant gram-negative bacteria, but at concentrations that are not toxic.
In mouse models, SF actually managed to kill a strain of bacteria that was found to be resistant to many existing drugs, all with minimal or no toxicity.
“Soil bacteria, in their quest to maintain their territory, have figured out during evolution how to make antibiotics capable of penetrating the armor of gram-negative bacteria. Streptothricins are one of the results of this race to ongoing armaments,” Kirby said.
“These compounds offer a distinctive solution for penetrating the defense mechanisms of Gram-negative pathogens.”
The precise details behind streptothricin’s attack are still unclear, but it appears that the antibiotic binds to gram-negative bacteria and disrupts its protein-making machinery in a way that other drugs do not.
If researchers can figure out how, it could help them develop an entirely new class of drugs for bacteria that have so far proven to be very resistant.
Kirby and his colleagues have already started exploring how to improve natural streptothricins, like SF, to work even better as superbug killers.
He says they “look forward to renewed interest in this historically important, but long forgotten class of antibiotics.”
The study was published in PLOS Biology.