New Antibiotic That Fights Resistant Bacteria Found

by Michael Keller

Scientists combing through soil have found a potential new class of antibiotics that appear to stop infections from drug-resistant microbes, an international team announced today.

The work, though still early in its development, is a bit of good news during a time when global health authorities warn about the dangers of more microbial species developing resistance to drugs. The World Health Organization, for instance, has sounded the alarm about a “post-antibiotic era, in which common infections and minor injuries, which have been treatable for decades, can once again kill.”

Discovery of the drug, now being called teixobactin, came after screening 10,000 compounds produced by soil-dwelling bacteria that had never been cultured. In a study published in the journal Nature, the team writes that the drug works by disrupting the construction of bacterial cell walls. They were pleasantly surprised to find that the way the drug worked didn’t seem to be stopped by bacterial strains that had evolved the ability to survive antibiotic attack.

“Early on, we saw that there was no resistance development to teixobactin,” said study coauthor Kim Lewis, the director of Northeastern University’s Antimicrobial Discovery Center. “This was, of course, an unusual and intriguing feature of the compound.”

Tanja Schneider, a microbiologist at Germany’s University of Bonn who coauthored the paper, says teixobactin works against bacteria like those that cause potentially fatal drug-resistant tuberculosis and Staph infections by finding a new target in these cells.

“We found that teixobactin targets the bacterial cell wall biosynthesis, which is the most prominent antibacterial target pathway,” Schneider says. “Teixobactin specifically binds to highly conserved cell wall building blocks.”

Instead of attacking proteins, which bacteria can more readily alter to prevent injury, the drug goes after lipids that make up the cell wall and cannot be easily changed. This difference means the drug won’t see resistance build up in bacteria for quite some time. The target lipid pathway “represents a particular Achilles’ heel for antibiotic attack,” Schneider says.

The discovery, which has shown success treating antibiotic-resistant bacterial lung and blood infections in animals, still has a long road ahead before it might be prescribed to patients. Lewis said it could start human clinical trials in two years if all goes well. Development, which will improve characteristics like the drug’s poor solubility in water, is expected to cost in the low hundreds of millions of dollars.

“If it makes it to the clinic, teixobactin will represent a new class of antibiotics,” Lewis says. “A new class is determined by a combination of chemical novelty and its mode of action. By these two criteria, teixobactin is a member of a new class.”

Neil Woodford, Head of Public Health England’s Antimicrobial Resistance and Healthcare Associated Infections Reference Unit, said the discovery of teixobactin could help to deal with the growing number of resistant microbes that respond to an ever-decreasing list of drugs. Still, because of the specific bacterial source of the drug, it can only treat infections by certain types of bacteria. In fact, the antibiotic was isolated from a gram-negative bacteria called Eleftheria terrae, and it can only kill gram-positive bacteria like those that cause Strep and Staph infections.

“Although this is a step forwards, this new discovery would not be suitable for treating infections caused by E.coli, Klebsiella or other Gram-negative bacteria,” Woodford said. “These are the focus of many concerns about antibiotic resistance and finding a new potential treatment for these would be a major breakthrough.”

There may be more discoveries on the heels of teixobactin that answer Woodford’s concerns. The method the team developed to screen bacteria should help in the search for new antimicrobial compounds. Up to 99 percent of bacterial species living in the wild have not yet been investigated for the chemicals they produce. Any one of these species that produces a useful compound could be another weapon in the constant arms race between humanity and the microbes that harm us.

“Pathogens are acquiring resistance faster than we can introduce new antibiotics,” says Lewis. “This is causing a human health crisis. We now have pathogens such as some strains of the microbacterium tuberculosis that are resistant to all available antibiotics.”

Top Image: Staphylococcus bacteria courtesy of Shutterstock.

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