New class of antibiotic could turn the tables in battle against superbugs

The powerful antimicrobial teixobactin was discovered using a new technique that could speed up the discovery of new antibiotics to tackle resistance.

Scientists have discovered a new class of antibiotic using a revolutionary procedure hailed as a game changer in the hunt for medicines to fight drug-resistant infections. The antibiotic, called teixobactin, kills a wide range of drug-resistant bacteria, including MRSA and bugs that cause TB and a host of other life-threatening infections.

It could become a powerful weapon in the battle against antimicrobial resistance, because it kills microbes by blocking their capacity to build their cell walls, making it extremely difficult for bacteria to evolve resistance.

“Teixobactin kills exceptionally well. It has the ability to rapidly clear infections,” said research leader Kim Lewis, director of the Antimicrobial Discovery Center at Northeastern University in Boston, US.

The public health threat of resistance was highlighted last year in a World Health Organisation report that warned the world was entering a “post-antibiotic era”. The UK’s chief medical officer, Sally Davies, has put antibiotic resistance on the government’s national risk register, alongside terrorist attacks and pandemic flu, and warned that without new antibiotics, more people will die after routine operation in the next 20 years. In December, a report commissioned by David Cameron warned that failure to tackle drug-resistant infections will cost the global economy up to £64tn ($100tn) by 2050.

In studies on mice, the new antibiotic wiped out infections of Staphylococcus aureus and Streptococcus pneumoniae, which can cause life-threatening blood and lung infections. It was also effective against Enterococcus, which can infect the heart, prostate, urinary tract and abdomen.

Most antibiotics are isolated from bacteria or fungi that churn out lethal compounds to keep other microbes at bay. But scientists have checked only a tiny fraction of bugs for their ability to produce potential antibiotics because 99% cannot be grown in laboratories.

Lewis’s group found a way around the problem by developing a device called an iChip that cultures bacteria in their natural habitat. The device sandwiches the bugs between two permeable sheets. It is then pushed back into the ground where the microbes grow into colonies.

The researchers found that after two weeks in the ground, the microbial colonies had grown enough to run tests on them. To do this, they covered the top of the iChip with layers of pathogens. Bugs that produced natural antibiotics revealed themselves by killing the pathogens above them.

Working with a Massachusetts-based company, NovoBiotic, and researchers at the University of Bonn, Lewis’s group screened 10,000 soil bacteria for antibiotics and discovered 25 new compounds. Of these, teixobactin was the most promising.

Teixobactin’s ability to kill bugs is only part of the attraction of the compound. Writing in the journal Nature, the scientists describe how none of the bacteria treated with the antibiotic showed signs of developing resistance.

The reason for the drug’s apparent resilience was discovered by Tanja Schneiderin Bonn. Most antibiotics target bacterial proteins, but bugs can become resistant by evolving new kinds of proteins. Teixobactin works differently. It launches a double attack on the building blocks of bacterial cell walls themselves. “That’s an Achilles’ heel for antibiotic attack,” Schneider said. “It would take so much energy for the cell to modify this, I think it’s unlikely resistance will appear this way.”

Though promising, Lewis said that years more work lie ahead before the drug could be available. Human clinical trials could begin within two years to check its safety and efficacy, but more development would follow that. At the moment the drug would have to be given as an injection, but an oral pill would be more attractive.

Another shortcoming of teixobactin is that it only works against bacteria that lack outer cell walls, known as Gram-positive bacteria, such as MRSA, Streptococcusand TB. It doesn’t work against Gram-negative bacteria, which include some of the most worrying antibiotic-resistant pathogens, such as Klebsiella, E. coli and Pseudomonas.

Despite these limitations, the discovery of the antibiotic, and the process used to grow previously ungrowable microbes, has raised hopes among researchers in the field.

“What most excites me is the tantalising prospect that this discovery is just the tip of the iceberg,” said Mark Woolhouse, professor of infectious disease epidemiology at the University of Edinburgh. “It may be that we will find more, perhaps many more, antibiotics using these latest techniques.”