Last updated April 18, 2018 at 9:22 am
A new class of powerful antibiotics has been discovered in soil samples, which will soon provide doctors with much-needed new weapons to combat drug-resistant infections.
Malactins have been successful against a range of multi-drug resistant pathogens, including against methicillin-resistant Staphylococcus aureus (MRSA). Credit: iStock
The new class of antibiotics, called malactins, has also revived interest in the medical uses of so called “natural products” made by bacteria – historically where most clinically useful antibiotics have been found.
But the strategy of drawing solutions from bacteria themselves has been largely abandoned during the past few years because of a lack of new discoveries.
Culturing most bacterial species has proven to be impossible, so only a tiny fraction of have been grown in laboratories, and even among these, many of the products they produce remain undetected.
Related: In a sort of investigatory end-run around the problem, a team led by Sean Brady of the Laboratory for Genetically Encoded Small Molecules at Rockefeller University in the US turned away from looking at specific species and took a more scatter-gun approach by collecting soil samples and seeing what could be found there.
To do this, the team developed a discovery platform that was not dependent on a known bacterial culture to work. Using this, they tested several soil samples, looking for biosynthetic gene clusters that contained calcium-binding elements that would indicate the possible presence of a particular type of antibiotic.
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The results were stunning. The biological signatures they searched for turned out to be abundant and diverse. Three quarters of sequenced soil samples came back positive for multiple clusters – of which, only 13 per cent bore similarities to those in already identified antibiotics.
In a paper published in the journal Nature Microbiology, Brady and his colleagues predict on the basis of their results that the majority of compounds present in soils globally is as yet undiscovered.
“Even within our large soil collection,” they add, “we have captured only a fraction of the biosynthetic diversity that exists within the calcium-dependent antibiotic family.”
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What they did succeed in capturing, however, should not be underestimated.
The malactins comprise a range of antibiotics that are effective against gram-positive pathogens – and have never been found in lab-based cultures.
Importantly, malactins are triumphant when pitted against a range of multi-drug resistant pathogens, including – at least in rodent-based trials – methicillin-resistant Staphylococcus aureus (MRSA).
This offers hope that grim predictions of a 10-fold increase in mortality due to untreatable infections by 2050 can be avoided.
Brady and colleagues note that although their discovery platform and sequencing methods are still in their infancy, both can be scaled up and automated. This, they say, will enable the continued systematic discovery of new “natural product” antibiotics without the need to culture target species in labs.
