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Within the Soil

Researchers led by Northeastern University's Kim Lewis report in Nature that they've developed a novel approach to find an antibiotic that appears to be able to kill pathogens.

Antibiotic resistance is an increasing concern as resistant bacterial strains have been cropping up faster than new ways to try to stop them have been found. As the New York Times reports, drug-resistant bacteria infect about two million people in the US each year, and 23,000 people die from those infections.

The search for new antibiotics has been hampered by the limits of the screening approaches. Many existing antibiotics have been found by sifting through soil for bacteria that naturally produce compounds that thwart other microbes. But only a small percentage of bacteria can be cultured and studied in the lab, leaving an untapped population to test.

Lewis and his colleagues report that they diluted their soil samples down so that one cell was in each aliquot. They then mixed those samples with agar and placed them into an iChip that was kept in a box with soil from where the samples were originally obtained. "The microbes are constrained to the agar, but they can still soak up nutrients, growth factors, and everything else they need from their natural environment," Ed Yong notes at Not Exactly Rocket Science. "And thus, the ungrowable grows."

Using this approach, Lewis and his colleagues uncovered a new antibiotic they've dubbed teixobactin. Teixobactin, they report in Nature, inhibits cell wall synthesis by binding to lipid II, the precursor of peptidoglycan, and to lipid III, a wall teichoic acid precursor.

The researchers note that teixobactin was effective against Gram-positive microbes. In vitro they showed that it could effectively kill Staphylococcus aureus, Mycobacterium tuberculosis, Clostridium difficile, and Bacillus anthracis. In mice, teixobactin was effective against methicillin-resistant S. aureus and Streptococcus pneumonia. It has not yet been tested people; Lewis tells the Times that such studies won't start for another two years.

Because of how teixobactin works — it binds to regions of lipid II and lipid III that are fairly constant across bacteria — Lewis and his colleagues say that it may be harder for bacteria to develop resistance against it. Though Stanford University's David Relman notes to the Times that "unsuspected mechanisms of resistance" do arise.

Still, Relman says that the paper "illustrates the amazing wealth and diversity of as-yet-unrecognized, potent, biologically active compounds made by the microbial world — some of which may have real clinical value.

"We've been blind to the vast majority of them because of the biased and insensitive methods we use to discover drugs," he adds.