New antibiotic could work for 30 years – if used right

19:00 07 January 2015 by Jessica Hamzelou

It's time to strike back. Antibiotic resistance has garnered headlines in recent years, but 2015 may be the year we make progress. Things are already looking promising, with two new antibiotics announced this week.

One, teixobactin, was discovered by employing a new twist on a tried and tested method: screening soil for bacteria that have evolved to kill their competitors. This is how most antibiotics in use today were discovered, but finding new drugs has proven difficult because only a tiny proportion of bacteria isolated from soil grow successfully in the lab under normal culturing conditions.

Kim Lewis at Northeastern University in Boston, Massachusetts, and his colleagues have hit on a startlingly simple method to solve the problem – just make bacteria feel at home in the lab.

By sandwiching the bacteria between two layers of the soil they were found in, separated by a semi-permeable membrane, they were able to drastically increase the chances of a bacteria growing – and producing antibiotics – in the lab.

Lewis's team used this system to screen 50,000 types of soil-dwelling bacteria for antibiotics that killed bugs like the hospital acquired infection MRSA and the bacteria that cause multi-drug resistant TB.

Different tactic

The screen identified teixobactin which seems to act on the "gram-positive" group of bacteria by targeting a lipid on their cell walls, along with other molecules.

This is different to how most existing antibiotics work. They typically target bacterial proteins but these alter over time as mutations creep into the DNA, leading to resistance.

Lewis's team thinks that if teixobactin was used to treat people, it would take at least 30 years for bacteria to develop resistance.

Other infectious disease experts are impressed, not only by the drug discovery but also by the possibility that this is just the beginning. "The properties of teixobactin suggest that resistance rates will be extremely low," says James Stach at Newcastle University, UK. Although resistance is eventually inevitable, doctors could manage the use of teixobactin to put it off for as long as possible, he says.

"Any report of a new antibiotic is auspicious, but what most excites me is the tantalising prospect that this discovery is just the tip of the iceberg," says Mark Woolhouse at the University of Edinburgh, adding that Lewis's team has found a way to look for antibiotics in the microbial "dark matter" that has so far been very difficult to study.

Scratching the surface

The second drug announced this week is being developed by Swiss drug company Novartis to treat multi-drug resistant TB. The drug works by targeting the same bacterial enzyme that an existing TB drug, isoniazid, hits but in a way that prevents the known mechanisms of resistance.

So far, both drugs have successfully treated infections in mice and human trials are planned for teixobactin in about two years' time. In the meantime, Lewis hopes to use the new culturing technique to search soil for other antibiotic candidates. "Soil has traditionally been a good source of antibiotics and has an enormous diversity of species," he says. "We've only just scraped the surface."

* * * Journal references:

Nature, DOI: 10.1038/nature14098 (teixobactin); Science Translational Medicine, DOI: 10.1126/scitranslmed.3010597 (Novartis)

* * *

Teixobactin (Nature)
Antibiotic Resistance
Teixobactin (Wikipedia)
Teixobactin: molecular structure

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