Big pharma gave up on soil bacteria as a source of antibiotics too soon, according to research published in the June issue of Microbiology. Scientists have been mining microbial genomes for new natural products that may have applications in the treatment of MRSA and cancer and have made some exciting discoveries.

“Over the last eight years we have been looking for new natural products in the DNA sequence of the antibiotic-producing bacterium Streptomyces coelicolor,” said Professor Gregory Challis from the University of Warwick. “In the last 15 years it became accepted that no new natural products remained to be discovered from these bacteria. Our work shows this widely-held view to be incorrect.”

In 1928 Alexander Fleming discovered penicillin, which was subsequently developed into a medicine by Florey and Chain in the 1940s. The antibiotic was hailed as a ‘miracle cure’ and a golden age of drug discovery followed. However, frequent rediscovery of known natural products and technical challenges forced pharmaceutical companies to retreat and stop looking for new molecules.

Currently the complete genetic sequences of more than 580 microbes are known. It is possible to identify pathways that produce new compounds by looking at the DNA sequences and many gene clusters likely to encode natural products have been analysed. ‘Genome mining’ has become a dynamic and rapidly advancing field.

Professor Challis and his colleagues have discovered the products of two cryptic gene clusters. One of the clusters was found to produce several compounds that inhibit the proliferation of certain bacteria. Three of these compounds were new ones, named isogermicidin A, B and C. “This discovery was quite unexpected,” said Professor Challis. “Our research provides important new methodology for the discovery of new natural products with applications in medicine, such as combating MRSA infections.”

The other product they discovered is called coelichelin. Iron is essential for the growth of nearly all micro-organisms. Although it is the fourth most abundant element in the Earth’s crust it often exists in a ferric form, which microbes are unable to use. “The gene cluster that directs production of coelicehlin was not known to be involved in the production of any known products,” said Professor Challis. “Our research suggests that coelichelin helps S. coelicolor take up iron.”

Many researchers have followed Professor Challis and his colleagues into the exciting field of genome mining. “In the near future, compounds with useful biological activities will be patented and progressed into clinical or agricultural trials, depending on their applications” said Professor Challis.

Source: Society for General Microbiology

G. L. Challis. Mining microbial genomes for new natural products and biosynthetic pathways. Microbiology; 154: 1555-1569 (not available at time of publication. Link goes to “Future Table of Contents”)

Josh says:

I’m not surprised at all that they found new potential antibiotics in soil bacteria. They are known for producing antibiotics, and it only makes sense that different species will produce different antibiotics. If they didn’t, they would become ineffective, like we’re seeing now with MRSA. Since I can’t read the paper, I’m don’t know if they known the mode of action of these antibiotics, but my impression from the press release is that it prevents the bacteria from uptaking iron.

Andrew says:

Soil bacteria genome mining is also interesting for potential insertional gene therapies to metabolize waste substances which accumulate in the body and contribute to aging. I’m excited to learn about those genes as they’re discovered.

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Researchers at MIT had recently tricked a bacteria, Rhodococcus, into producing two variations of a previously unknown antibiotic by making it fight for survival against another bacteria, Streptomyces. The original paper can be found in the Journal of the American Chemical Society. The researchers believe the genes encoding the enzymes necessary to produce these new antibiotics are on or related to a megaplasmid (a sequence of DNA) that Rhodococcus acquired from Streptomyces.

When I originally saw this, I thought they had coaxed a bacteria into evolving a new antibiotic rather than getting it to produce one it already had the genes for. It would still be an interesting approach, though to develop new antibiotics or modifications to existing ones.

I was reading this article and I thought: what if bacteria could designed with every sunlight-capturing pigments —this rare form of chlorophyll, “green” chlorophyll, beta-carotene, etc.— to capture the widest possible light spectrum? It would be able to convert an absurd proportion of sunlight energy into chemical energy. If this was coupled with an up-regulation of the fatty acid synthesis pathway, then these bacteria would be used to directly convert light energy into oil at a very high efficiency.

Unlike existing plant alternatives, the raw bacteria oil would be a transportable, near-end product that would save us from having to invest in an extensive new refining and transportation infrastructure. Even better, the bacteria could be hypothetically grown anywhere: massive hydroponic plants in the desert, miniature hydroponic tiles on buildings, even on Antarctic ice or quarantined open ocean.

Certainly, this bacteria would be far more efficient than terribly energy-inefficient, agriculturally-exhaustive corn ethanol or dangerous, difficult-to-transport hydrogen.