25 January 2015

From mud to medicine A major breakthrough in antibiotics

The discovery of a new antibiotic with a unique has altered the perspective in the endless war on disease. The recent announcement of the discovery ofhas led to hopes that an entirely new class ofthat does not trigger drug resistance could be deployed, by using a new approach which makes it easier to culture antibiotics. There have been no new classes of antibiotics released as prescription drugs for 32 years. Although new antibiotics have been discovered in that time, none had promising drug potential and most could not be easily cultured. In that time, a wide range of bacteria has mutated to develop resistance to most of the commonly used antibiotics. This has led to the resurgence of diseases such as pneumonia and tuberculosis in new "superbug", drug-resistant forms, as well as the emergence of new superbugs such as (Methicillin-resistant Staphylococcus aureus) and the so-called Delhi superbug. Drug-resistant superbugs kill an estimated 700,000 people every year.

The new antibiotic, teixobactin, seemed to tackle drug-resistant superbugs effectively in its initial clinical trials with mice. It also seems to do this without setting up detectable resistance within the bacteria. The implication is that this antibiotic may actually have evolved in such a fashion that pathogens will not develop immunity to it even after long exposure.

What is more, teixobactin was isolated and cultured using new methods. There is the promise that more new powerful antibiotics, with good drug-potential, might be found using such an approach. It is early days and it may take two years or more before teixobactin is tested and cleared for clinical trials with humans. It could take five years or so to become a prescription drug, assuming all goes well. But this discovery definitely creates the possibility of deploying new weapons against superbugs, just when it looked as though drug-resistant bacteria would gain the upper hand.

The researchers who found the drug and pioneered the new approach were drawn from several academic institutions. The team was led by Kim Lewis and Slava Epstein, of Northeastern University, Boston, who co-authored the technical paper, published in Nature. It included scientists from the University of Bonn, and researchers from pharmaceutical development lab, NovoBiotic Pharmaceuticals, set up by Prof. Epstein and Prof. Lewis.

Antibiotics have generally been discovered by screening micro-organisms present in the soil. Penicillin was found by accident in bread mould, back in 1928. But very few natural antibiotics can be cultured in the laboratory and many have dangerous side-effects. The team has developed new means of growing and studying bacteria and antibiotics in their natural environment - literally in dirt. They have built a tool they call the ("isolation chip") which allows single cells of an antibiotic to be isolated and cultured. They have so far found 25 new antibiotics, of which teixobactin is the most promising. The new antibiotic is produced by a bacterium called eleftheria terrae, which was found and cultured using iChip technology in a field of grass. Teixobactin has an unusual action, which allowed it to destroy a range of drug-resistant pathogens in mice by multiple attacks on the cell walls. Despite lengthy exposure, these pathogens did not mutate to develop strains that were subsequently resistant to teixobactin's action. Teixobactin itself will need to be studied in much greater detail.

The iChip (which is patented by Northeastern University and licensed to NovoBiotic Pharmaceuticals) will need to be deployed on a wider scale across multiple geographical and climatic regions to see if it can be used to culture more such drugs. If these antibiotics do work, they will have to be deployed with care to ensure that pathogens don't eventually develop some new resistance to their actions. Despite those caveats, this is potentially an enormous breakthrough which could transform drug research.

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