Turning to dirt for antibiotics in the fight against superbugs

Chemical biologist Sean Brady at The Rockefeller University in New York City and his team in 2018 discovered new antibiotics, called malacidins, by applying genetic sequencing techniques to bacteria in soil samples.

(CNN)Think about aphids — those little, green, garden-destroying bugs. The bane of the begonia. But aphids exist in an ecosystem. Which is to say, those little suckers have enemies. When gardeners see aphids, it's often ladybugs to the rescue.

There is another plague out there right now: the antibiotic-resistant bacteria currently making a home in our health care system that kills thousands each year.
But by thinking like a gardener and looking to the ecosystem those microbes originally came from, we may be able to find new ways to fight them.
For instance, researchers at Vanderbilt University recently unearthed a new kind of chemical compound that may one day help fight off antibiotic-resistant bacteria. The source? Dirt.
    Dirt, it turns out, contains an entire microbial ecosystem, with a wealth of intriguing compounds. And while there are major hurdles between discovering a new drug and using it, scientists are hopeful new techniques could pay off.

    Stuck in the mud

    Antibiotic-resistant microbes, commonly called superbugs, have become a major health problem across the world. More than 2.8 million infections happen every year in the United States alone; more than 35,000 people will die from those infections.
    The answer for an infection is often antibiotics. Or stronger antibiotics.
    But we're not the original inventor of this class of compounds — for time immemorial, antibiotics have been deployed by the microbes themselves. Microbes, such as the myriad species of fungi, bacteria and other critters that live in the soil, live in a complex ecosystem where chemical defenses are often necessary in order to fend off or attack competitors.
    In fact, soil was actually one of the great historical sources for new antibiotics.
    "The vast majority of antibiotics we use today come from growing bacteria out of soil," said Sean Brady, a chemical biologist and professor at The Rockefeller University in New York City. Though we came up with ways to make them ourselves, it was in dirt that these antibiotics were first discovered.
    Streptomycin, which is often used to treat tuberculosis, came from a sample of New Jersey soil back in the 1940s, for instance.
    At the time, a wealth of new medicines seemed just within reach.
    Unfortunately, it turned out that soil microbes are finicky. Only a handful grow well in traditional laboratory setups, and what we could get out of them was limited. Stuck discovering the same compounds over and over again, the pharmaceutical industry's focus shifted to tweaking the antibiotics we already had.

    Returning to our roots

    However, in the last few years, a number of researchers have been going back to the soil with new techniques.
    One potential breakthrough came when Kim Lewis, a microbiologist and university distinguished professor at Northeastern University, and his colleague Slava Epstein, a professor of biology, figured out how to "domesticate" wild microbes. The duo loaded soil bacteria into a special device called the "iChip" (short for isolation chip), then buried it back into their native soil until the bacteria grew into usable colonies.
    Microbiologist Kim Lewis of Northeastern University and Yu Imai, a postdoctoral research associate, observe a petri dish encasing darobactin, a new type of antibiotic that can selectively kill gram-negative bacteria in October 2019.
    One compound Lewis and Epstein's team discovered, called teixobactin, originally came from a grassy field in Maine. Teixobactin got a write-up in Nature in 2015 and was hailed as the first truly novel antibiotic to be discovered in nearly 30 years.
    Brady and his team announced a few years later that they had managed to discover a class of compounds they called malacidins, again from soil samples. In this case, the researchers skipped growing finicky bacteria altogether, instead processing bits of the bacterial genome from the soil directly, a technique known as metagenomics.
    These discoveries, and others like them, could represent major breakthroughs in fighting antibiotic-resistant bacteria.
    Neither teixobactin nor malacidins are ready for use yet, though.
    Teixobactin is currently being studied by a company called NovoBiotic Pharmaceuticals, which said in an email statement that the compound is in preclinical development, with the goal to submit it for FDA approval to begin testing in humans in 2022.
    Brady, meanwhile, said his research team is continuing to investigate the malacidin family of compounds and are hoping to narrow down the candidates to the ones that would have the best chance of working in humans before moving toward trials.
    "You don't always want to go with the very first thing you find," he said.
    The truth is, for all their potential, these drugs may still fail. Both Lewis and Brady, as well as industry experts, caution that the pipeline for turning these discoveries into drugs can be long and, it turns out, pretty leaky.

    The leaky pipeline

    "It's exciting to have these potential new novel classes of drugs, but there's a lot of work that needs to be done to take it from soil to patient," said Wes Kim, a drug development expert and senior officer at Pew Charitable Trust's Antibiotic Resistance Program.
    The trust has been advocating and supporting the development of new antibiotics for a long time. The nonprofit institution is committed to seeing these kinds of discoveries come to light.