Antibiotic hunters hit pay dirt


The solution to antibiotic resistance could come from soil. Paul Biegler reports.


When searching for new antibiotics, getting down and dirty pays dividends.
When searching for new antibiotics, getting down and dirty pays dividends.
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It might come as a surprise to learn that dirt, that canonical cause of infection, is also a megafactory for antibiotics.

Research, published in the journal Nature Microbiology, has exploited that facility to produce a new class of antibiotics, dubbed “malacidins”, which are not only effective against that bane of modern hospitals, Golden Staph, but could pave the way for exponential increases in the rate of new antibiotic discovery.

Although some antibiotics are fully synthesised in the lab, most have come from the natural world, produced by fungi and bacteria as weapons to fight off other bugs that compete for nature’s microbe-sustaining goodies.

Dirt, as anyone with a passing knowledge of infection control understands, is positively teeming with bacteria, for whom killing off rivals is pretty much a full-time job.

The upshot, write the researchers, led by Sean Brady, a chemical biologist at the Rockefeller University in New York, is that “environmental microbes are in a continuous antibiotic arms race that is likely to select for antibiotic variants capable of circumventing existing resistance mechanisms.”

That could prove very useful; global deaths from antibiotic-resistant infections are predicted to rise more than tenfold, to 10 million a year, by 2050.

The team took their lead from the action of daptomycin, an antibiotic that uses calcium to disrupt bacterial cell walls, and distinguishes itself as a particularly strong performer against multidrug-resistant bugs.

They used a gene sequencing technique to probe samples, from their more than 2000-strong collection of soils, for antibiotics exhibiting a similar calcium-dependent action. This technique of widely interrogating the so-called “soil metagenome” is still in its infancy, but is replacing traditional culture methods which have fallen by the wayside as rates of new antibiotic discovery dwindled.

The researchers, quite literally, struck pay dirt.

They discovered a previously unknown class of antibiotic that deploys calcium in a novel way against bacterial cell walls. They named it, rather unparsimoniously, metagenomic acidic lipopeptide antibiotic-cidins – malacidins to you and me.

Applying malacidin-A to rat wounds infected with Golden Staph (more formally known as methicillin-resistant staphylococcus aureus), a bug whose presence in hospital patients generally presages the arrival of an infectious disease SWAT team, was decisive.

“At 24 and 72 [hours] post infection, malacidin-A treatment resulted in no observed bacterial burdens in the wounds,” the researchers report.

There were, however, yet further good tidings.

“Our experimental efforts to induce resistance to malacidin in the laboratory have so far been unsuccessful. Even after 20 days of exposure to sub-lethal levels of malacidin-A, we did not detect any malacidin-resistant S. Aureus,” they write.

The discovery brings to mind a homily from Brazilian author Paolo Coelho’s novel The Alchemist, which, for infectious disease specialists contemplating the prospect of a trove of undiscovered, resistance-proof antibiotics, could well have new meaning.

The treasure, Coelho famously wrote, is buried beneath your feet.

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Paul Biegler is a philosopher, physician and Adjunct Research Fellow in Bioethics at Monash University. He received the 2012 Australasian Association of Philosophy Media Prize and his book The Ethical Treatment of Depression (MIT Press 2011) won the Australian Museum Eureka Prize for Research in Ethics.
  1. https://www.nature.com/articles/doi:10.1038/s41564-018-0110-1
  2. https://www.nature.com/articles/doi:10.1038/s41564-018-0110-1
  3. https://amr-review.org/
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