An antibiotic developed about 80 years ago before being abandoned and forgotten could once again offer exciting new solutions, this time against the emerging threat of drug-resistant superbugs.
Half of the antibacterial drugs we use today are variations of compounds discovered nearly a century ago, during the “golden age” of antibiotics.
One of them, 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 do not have a 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 subsequently buried in the scientific literature.
This year, Harvard University pathologist James Kirby and colleagues dug it up, 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,” he said. Kirby told ScienceAlert in May.
Nourseothricin is a natural product made from 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 exhibit toxic effects on kidney cells in the laboratory, Kirby and colleagues have now established that this is not the case for SF. This compound remains very effective at killing drug-resistant Gram-negative bacteria, but at concentrations that are not toxic.
In mouse models, SF successfully killed a strain of bacteria that has proven resistant to many existing drugs, all with minimal to no toxicity.
“Soil-dwelling bacteria, in their quest to maintain their turf, have figured out over eons of evolution how to make antibiotics that can penetrate the armor of Gram-negative bacteria. Streptothricins are one of the results of this ongoing arms race,” Kirby said.
“These compounds offer a distinctive solution to penetrate the defense mechanisms of Gram-negative pathogens.”
The precise details behind the attack of streptothricin are not yet clear, but it appears that the antibiotic binds to Gram-negative bacteria and disrupts its protein-producing mechanism 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 highly resistant.
Kirby and his colleagues have already begun exploring how to improve natural streptothricins, like SF, to work even better as superbug killers.
He said they “look forward to a renewed interest in this historically important, but long forgotten, class of antibiotics.”
The study was published in Biology PLOS.
An earlier version of this article was published in May 2023.
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