An antibiotic developed nearly 80 years ago, before being abandoned and forgotten, may offer new solutions, this time for the emerging threat of drug-resistant bacteria.
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Half of the drugs we use today to kill bacteria are variations of compounds discovered almost a century ago, during the “golden age” of antibiotics.
A drug called streptothricin was isolated in the 1940s, attracting attention for its potential value in treating infections caused by what are called gram-negative bacteria.
Unlike gram-positive bacteria, these microorganisms lack a resistant cell wall that many antibiotics target. Finding alternatives has been one of the major challenges for the pharmaceutical industry.
In 2017, the World Health Organization (WHO) published a list of the most dangerous, drug-resistant pathogens in existence. Most of them were gram-negative bacteria.
Although streptothricin had the potential to kill bacteria, it failed to catch on. It was found to be highly toxic to kidney health in an initial study, and was thus buried in the scientific literature
This year, pathologist James Kirby of Harvard University and his colleagues are digging it up, exploring its potential under a new name – nourseothricin.
“Now, with the emergence of multidrug-resistant microbes, for which there are few, if any, effective antibiotics to treat, it is time to reexamine and explore the possibility of what we have neglected in the past,” Kirby told ScienceAlert in May.
Nurceothricin is a natural product produced by gram-positive soil bacteria. It is actually a mixture of antibiotics, which have individual names such as streptothricin F (SF) and streptothricin D (SD).
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Although nourseothricin and SD exhibit toxic effects on cells in the laboratory, Kirby and colleagues have now shown that this is not the case for SF. This compound is still highly effective in killing drug-resistant gram-negative bacteria, but at concentrations that are not toxic.
In experiments on mice, SF was actually able to eliminate all bacteria that have proven resistant to many existing drugs, with little or no toxicity.
The exact details behind attack are still unclear, but it appears that the antibiotic binds to gram-negative bacteria and alters their protein production machinery in a different way than other drugs.
If researchers can figure out how, it could help them develop a whole new class of drugs for bacteria that have so far proven resistant. Kirby and colleagues have already begun exploring how to enhance natural streptothricins, such as SF, to work even better as killers of resistant bacteria.
He said they look forward to a resurgence of interest in this historically important but neglected class of antibiotics. The study was published in PLOS Biology.
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Source: sciencealert
