Dirt: the answer to antibiotic resistance?

The search for new antibiotics has taken us to soil bacterium.

It has been nearly 30 years since the last new class of medically viable antibiotics was discovered. Since then, bacteria have developed immunity to most common drugs, and the pool of available antibiotics that are still effective is thinning at a greater rate than we can replenish it. Pathogens evolve resistance quickly because they have short generations, although the process is sped up by improper use of antibiotics, such as their routine inclusion in livestock fodder. But this is only half the story. Most antibiotics currently in use come from cultured bacteria –those that can be grown in the lab–, which account for a mere 1% of all microbes. Now scientists are turning to the remaining population of bacteria that refuse to grow on their Petri dishes.

Kim Lewis and fellow researchers of Northeastern University, in Boston, came up with a way of culturing these uncooperative microorganisms in their natural environment. They diluted soil samples so that individual bacteria became isolated in the chambers of a chip-like device. When buried in soil, nutrients and growth factors necessary for cell proliferation could permeate the chambers while the bacteria remained trapped. This original method, reported in Nature, allowed the team to screen 10,000 different substances secreted by soil-dwelling bacteria for antimicrobial activity. Twenty-five potential antibiotics were found this way, but one particular chemical, which they have named teixobactin, stands out.

Teixobactin targets fatty molecules necessary for bacteria of the Gram-positive family to build up a cell wall. This makes it an excellent killer of many pathogenic microbes such as Mycobacterium tuberculosis (M. tuberculosis) and Staphylococcus aureus (S. aureus), both of which cause severe human diseases. But more importantly, Prof Lewis believes that this drug’s mechanism of action has evolved specifically to elude antibiotic resistance. Bacteria can rapidly develop resistance to antibiotics that target proteins, as mutations in their DNA change the shape of these proteins, making them unrecognisable to the antibiotic. However, as this drug acts on essential lipids, which are highly conserved among Gram-positive bacteria, the pathogens are unlikely to shake it off anytime soon. The new drug has already proven more effective than vancomycin, a similar antibiotic used to combat resistant strains of methicillin-resistant S. aureus (MRSA); during trials it was able to clear lethal doses of the pathogen in live mice at lower concentrations. Human tests will follow before the drug can be used clinically.

The novel discovery methods and unique mechanism of teixobactin herald a new age in the hunt for antibiotics. Scientists are optimistic that many more chemicals with similar properties are waiting to be found in our soil’s uncultured bacteria – and they now have the means to get to them. Since the publication of the study, biologists from Rockefeller University have started a citizen science project called “Drugs from Dirt”. They encourage members of the public to send soil samples from across the globe in order to sequence microbial genes that may encode potential antibiotics. The project’s creators hope to produce a complete map of chemicals from the world’s soil bacteria that will guide future discoveries.

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