With bacteria evolving to resist antibiotics faster than scientists can concoct new drugs, the fight against resistant infections in hospitals and food supplies is a tough one to win. But a newly discovered antibiotic may prove irresistible to bacteria.
Every time an antibiotic is used, bacteria are getting to know it a little better. And eventually, they develop methods to fight it. But because of its unique method of action, this new antibiotic could keep working for longer than any other before bacteria even started to get wise — maybe even longer than 30 years.
That’s the promise of a study published Wednesday in Nature. But the antibiotic, called Teixobactin, is still a couple years away from human trials, and at least four years away from your medicine cabinet. And unfortunately, it doesn’t treat some of the world’s nastiest bugs. But it could still make a huge impact on health.
Along with his colleagues and the help of a biotech start-up called NovaBiotic Pharmaceuticals, Northeastern University professor Kim Lewis tapped into a largely unexplored treasure trove of new antimicrobials: The dirt.
Dirt from a grassy field in Maine, to be specific.
Most microbiologists only ever work with around 1 percent of microbes — the ones that will grow politely in the lab. But the rest refuse to grow on petri dishes. But there are potential antibiotics all over the world being created by plants, fungi, and microorganisms. Lewis and his colleagues sandwiched soil between two semi-permeable membranes, effectively tricking soil microbes into growing in a “natural” environment that was actually a lab culture.
Among the 10,000 organisms and 25 antibiotics they grew in this new type of culturing method is Teixobactin. It successfully obliterated MRSA and drug-resistant TB in cell cultures and in mice, and did so without any signs that the bacteria might become resistant to it.
And, importantly, it did so without killing the mice. That was actually a concern: The drug performed so well in cell cultures that the researchers assumed it would blindly kill mammalian cells along with bacteria. But the mice, who were infected with MRSA and given pneumonia, didn’t die or have notable side effects.
The world needs new antibiotics, and several new classes of them — distinguished by unique chemistry and new methods of action against the microbes they fight — are in the research pipeline. But because antibiotics are expensive to develop and don’t make much money (after all, over-prescribing simply speeds up the formation of bacterial resistance), true innovation comes rarely. If Teixobactin makes it to the market, it could be the first new class of antibiotic in decades.
Teixobactin works by targeting the building blocks of the bacterial cell wall. Most antibiotics target proteins inside the cell to disrupt it, but Teixobactin binds to two different lipids that are necessary in cell wall production. So even if one developed resistance, the other could still be targeted. In traditional tests to coax bacteria into mutating resistance to a drug, the researchers just kept being able to kill the bacteria.
But all good things must eventually come to an end.
“They didn’t find resistance in a couple of simple tests, so it won’t happen in a minute, but there is no compound on this planet that bacteria will not develop resistance to,” Said Richard Novick, an NYU Langone Medical Center professor who wasn’t involved in the study. “But it would certainly happen more slowly with this one.”
And unfortunately, the drug’s genius mechanism is also its biggest flaw. It can only target so-called gram-positive bacteria, like staph, strep and TB, because they’re unprotected once their cell walls start to break down. Gram-negative bacteria like E. coli and the organisms that cause many sexually transmitted infections have an outer membrane that Teixobactin can’t penetrate. That’s probably a safety mechanism built-in by the gram-negative bacteria that created Teixobactin in the first place.
But on the other hand, if the only resistance that exists to the antibiotic is gram-negative membrane, gram-positive bacteria are out of luck.
“It looks like it evolved to be resistance free,” Lewis said during a Nature news briefing on Tuesday. “I think it should be used as broadly as possible, because it’s exceptionally well-protected from resistance development.”
He pointed out that Vancomycin, which also works by targeting a cell wall building block, was on the market for 30 years before cases of resistant pathogens were reported. And in Vancomycin’s case, the resistance came from the organism that originally produced the antibiotic. Bacteria fending off Teixobactin have no such mechanism to borrow.
Novick praised the study, but was more conservative about Teixobactin’s potential uses.
“The danger in a drug like this is that the minute it gets released, everyone and their cousin will want to use it, and that would be a catastrophe,” he said. “If I made the rules, I’d rule that it not get used outside the hospital, and not without supervision.”
By limiting the world’s exposure to the drug, doctors can stave off resistance even longer — and save Teixobactin as a much-needed last resort for gram-positive infections.
But not to worry. Lewis’ method of digging around the dirt for drugs has already yielded several other promising microorganisms, including a potential cancer drug — so it’s likely that the research team has unlocked a great new resource for drug discoveries.
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