New antibiotic candidate shows promise

A compound isolated from soil might have the right stuff for fighting troublesome bacteria, researchers report January 7 in Nature. While still far from being declared a true antibiotic drug, the compound teixobactin tested well in lab dishes against Clostridium difficile, a microbe high on doctors’ most-wanted list, as well as against bacteria that cause anthrax and tuberculosis.

In mice, teixobactin also knocked out strep microbes without showing any adverse effects in the animals. And also in mice, it killed staph bacteria that were resistant to other drugs. In these tests, the target bacteria showed no hint of developing resistance to teixobactin itself. That’s important because too often bacterial mutations engender resistance to treatment, rendering many drugs ineffective and outpacing Big Pharma’s efforts to come up with alternative drugs.

Teixobactin works by interrupting the biosynthesis of building blocks bacteria need for constructing their cell wall, says study coauthor Kim Lewis, a biochemist at Northeastern University in Boston. The breakdown of the cell wall destroys the bacteria’s defenses, killing them. The new compound’s lethality is directed at one broad class of microbes called gram-positive bacteria. It is not effective against some microbes, such as E. coli, a gram-negative bacterium.

The oft-prescribed antibiotic vancomycin also attacks cell wall biosynthesis. Microbes needed nearly 40 years — a long time in the world of bacteria — to gin up resistance to that drug, notes Gerard Wright, a biochemist at McMaster University in Hamilton, Ontario, who was not involved in the study. “In a field dominated by doom and gloom,” he writes in a commentary in Nature, the new finding “offers hope that innovation and creativity can combine to solve the antibiotics crisis.”

Researchers are excited about the finding in part because the method by which they discovered this compound might yield other drug candidates. Bacteria in soil, where teixobactin was found, naturally make antibiotics to fend off other bacteria. In the past, scientists have tried culturing such microbes in a lab but many do not readily grow in culture. In the new study, Lewis and colleagues first identified promising bacteria and then grew them in patches of soil.

After weeks of building a colony of desirable bacteria that way, the team transferred the operation to lab dishes and mass produced the bacteria. A microbe called Eleftheria terrae makes the potent compound teixobactin.

Teixobactin will require up to two years of additional testing before it can reach human trials, probably as an injected drug. Tests in people will then take a few more years, Lewis says. But he is optimistic. “Teixobactin will represent a new class of antibiotics,” he predicts. “This represents something of a paradigm shift in our minds because we thought resistance was inevitable.”  He says bacteria usually gain resistance to a drug by modifying the molecules targeted by those drugs, but the building block bound by teixobactin doesn’t lend itself to that. “It would take so much energy for the cell to modify this motif that I think it’s unlikely that resistance will appear that way,” he says.

Editor’s note: This article was updated January 14, 2015, to correct the spelling of Eleftheria in the main text.