Microbe found in grassy field contains powerful antibiotic

Shaky sensor. A cantilever (c) covered with bacteria (b) shakes up and down as the bacteria metabolize on its surface, and the vibrations are detected by a laser beam.

(left) Sandor Kasas; (right) Sandor Kasas and Giovanni Longo

For much of the last decade, a team of researchers in Boston has eagerly exhumed and reburied dirt. It’s part of a strategy to access an untapped source of new antibiotics—the estimated 99% of microbes in the environment that refuse to grow in laboratories. Now, their technique has yielded a promising lead: a previously unknown bacterium that makes a compound with infection-killing abilities. What’s more, the team claims in a report out today, the compound is unlikely to fall prey to the problem of antibiotic resistance. That suggestion has its skeptics, but if the drug makes it through clinical trials, it would be a much needed weapon against several increasingly hard-to-treat infections.

Many existing antibiotics, including penicillin, were identified by cultivating naturally occurring microorganisms—bacteria often try to kill each other with chemical warfare, it turns out. But the supply of novel microbes that will grow in a lab has been largely tapped out. In 2002, microbiologist Kim Lewis, along with his colleague at Northeastern University in Boston, microbial ecologist Slava Epstein, described a new technique for coaxing bacteria to grow: Put soil samples into tiny chambers sandwiched between permeable membranes and return these contraptions to the ground. The bacterial strains confined in the chambers will form colonies—thanks in part, the team suspects, to growth factors from neighboring organisms that cross the membranes. The resulting “domesticated” colony can then be removed from the chamber and sometimes will more readily call a petri dish home.

The researchers used a version of this approach to isolate and grow new bacterial colonies—many scooped out of soil in the backyard of microbiologist Losee Ling, who leads research and development at the startup company NovoBiotic Pharmaceuticals, formed to commercialize their approach. To test the antibacterial properties of these soil microbes, the team let each of them duel in a lab dish with Staphylococcus aureus, a cause of serious skin and respiratory infections. Then they isolated and tested individual compounds—10,000 in all—from the bacteria that most effectively killed the staph bacteria.

One bacterium, from a grassy field in Maine, produced a compound with powerful abilities to kill a variety of other bacterial species, including many human pathogens. Moreover, these pathogens failed to develop resistance to the compound: There were no surviving individuals that had evolved to withstand its attack. (Resistance usually develops when a small percentage of microbes escape an antibiotic because of a mutation and then those bacteria multiply.) Lewis initially took this total devastation as a discouraging sign—the mark of “another boring detergent.” (Bleach, after all, is a strong antibiotic, but it’s a little too effective at killing any surrounding cells.) However, it turned out that the new compound, which the group named teixobactin, was not toxic to human cells in a dish.

And it showed other qualities of a good antibiotic, the team reports online in Nature. On bacteria growing in lab dishes, it outperformed vancomycin, a drug long relied upon to treat the obstinate methicillin-resistant Staphylococcus aureus (MRSA), by a factor of 100, Lewis says. In mice infected with MRSA, injections of teixobactin led to a 100% survival rate at lower doses than vancomycin.

The compound isn’t effective against so-called Gram-negative bacteria, increasingly feared in hospitals for their resistance to existing drugs. But the authors suggest it could be of great value to people fighting MRSA, tuberculosis, and infections with rare-but-nasty Enterococcus bacterial strains that aren’t responding to available drugs.

These results offer hope that other promising agents await discovery in the soil, says Helen Zgurskaya, a biochemist at the University of Oklahoma, Norman, who studies how bacteria become susceptible to antibiotics. “This study demonstrates that unculturable bacteria … have new, previously unrecognized, biologically active compounds,” she says. “We now have proof of principle, and I hope more people will follow this path.”

But will teixobactin, like so many promising agents before it, eventually meet its match in a resistant strain? Lewis and his co-authors believe it’s unlikely. Collaborators at the University of Bonn in Germany figured out that teixobactin works by interfering with two important lipids that bacteria use to build their cell walls. (A few other known compounds work in a similar way, including vancomycin.) The authors suggest that bacteria are unlikely to evolve ways to resist teixobactin because it acts on two different targets that are highly conserved across many bacterial species and are not easily changed.

Bacteria did eventually develop resistance to vancomycin, though Lewis points out that it took 30 years. And he thinks this compound may have even better odds than vancomycin. Based on the team’s screens of soil, the compound seems to be relatively rare, so Lewis doubts that many bacteria have evolved to produce an enzyme that could destroy it.

That’s a logical argument, says Michael Fischbach, a microbiologist at the University of California, San Francisco. But there are many paths to developing resistance, and if any bacterium out there makes a substance with even limited activity against teixobactin, that could be “the starting point for evolution,” he says. “The results that they got were promising, no doubt about it,” he concludes, but “I would never underestimate the wiliness of bacteria.”