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Tuesday, January 13, 2015
New antibiotic could be game changer in fight against resistance
An antibiotic with the ability to vanquish drug-resistant pathogens has been discovered, through a soil bacterium found just beneath the surface of a field in Maine. The discovery, coming at a time of increasing concern over use and curbs to antibiotic use, could lead to considerable benefits for human medicine and, by implication, for veterinary medicine.
A team from Northeastern University in Boston, Massachusetts, have reported in Nature that the antibiotic, which they have named teixobactin, is active against the bacterium methicillin-resistant Staphylococcus aureus (MRSA) in mice, and a host of other pathogens in cell cultures. If the compound behaves similarly in people, it may prove to be a much-needed triumph in the war against antibiotic resistance.
The researchers used a device to discover teixobactin that has the potential to reveal further undiscovered antibiotics as it enables “unculturable” microbes to thrive in the laboratory, and so makes it easier to discover bacteria that naturally produce compounds deadly to other pathogens.
Mining dark matter
Many of the most successful antibiotics were found by scientists who trawled microbial communities for bacteria capable of killing their brethren. But the researchers missed the type that produces teixobactin, Eleftheria terrae, as well as many more candidates – known collectively as microbial “dark matter” – because of their reluctance to adapt to life on a petri dish.
The device used to identify teixobactin, called the iChip, works by sorting individual bacterial cells harvested from soil into single chambers. The device is then buried in the ground. Several molecules in that environment are able to diffuse into the iChip, allowing the bacteria to thrive in a more natural setting than a petri dish. Typically, only about 1 percent of microbes in a soil sample are able to grow in the laboratory. The iChip extends that to 50 percent, offering the possibility of further discoveries.
The researchers tested 10,000 of the resulting bacterial colonies to see whether any were able to halt the growth of S aureus. That search yielded 25 potential candidates, but teixobactin has been the most attractive so far.
Research team leader Kim Lewis believes that the importance of teixobactin lies in the fact that it will be difficult for pathogens to develop resistance against it.
Unusually for an antibiotic, he says, teixobactin is thought to attack microbes by binding to fatty lipids that make up the bacterial cell wall, and it is difficult for a bacterium to alter such fundamental building blocks of the cell. By comparison, most antibiotics target proteins and it can be relatively easy for a microbe to become resistant to those drugs by accumulating mutations that alter the target protein’s shape.
Seeing a commercial product come to market could still be some time away, however.
While teixobactin has been tested in mice and has yet to show any toxic side effects, demonstrating safety in humans will be important, notes Barry Einstein, senior vice-president of scientific affairs at Cubist Pharmaceuticals, which attempted mining dark matter a decade ago.
Toxicity is still the leading cause of failure in turning a potential antibiotic drug into a real drug, and disappointingly, teixobactin has disappointed in its failure to kill gram-negative bacteria, however Einstein believes there is reason to be optimistic about teixobactin because it is rare to find a single molecule with so many promising properties.
Need for more medicine choices
Both human and veterinary medicine need new antibiotics;however, research in the field has been significantly reduced over recent years.
Resistance is spreading faster than the introduction of new compounds into clinical practice, causing a public health crisis, and the discovery of teixobactin comes amid growing warnings from public-health experts about the dangers of antibiotic resistance, and decreasing options for treatment.
In 2014, the World Health Organization declared that the post-antibiotic era – a time in which people could die from ordinary and minor injuries – could begin this century.
In human medicine doctors are repeatedly being urged to prescribe antibiotics with greater caution, while in agriculture, producers are facing growing curbs as, use of antibiotics in livestock, it has been argued, is leading to antibiotic resistance in human medicine.
Agriculture has been at the forefront in efforts to reduce antibiotic use, particularly where drugs can be used across animals and humans, however, it is not the case that all agricultural use antibiotics are used in human medicine, take for example ionophores.
There are also some macrolides, which are also derived from soil organisms, for example tyvalosin, marketed by Eco Animal Health as Aivlosin, and used in the poultry industry against mycoplasma spp. Company global marketing manager Marc Coulier notes that tyvalosin is not used in human medicine and is only administered in low doses for a rapid response as and when issues arise, meaning that its use can help producers align with responsible use initiatives.