Finding these small molecules — known as natural products — has traditionally been a slow affair. Microbes typically make natural products in exquisitely tiny amounts, and they don’t rely on a single gene to do so. Instead, microbes need dozens of different proteins made by different genes to craft a natural product. Dr. Fischbach and his colleagues set out five years ago to speed up the search. They wrote a software program that learns how to recognize the genes for natural products. Those genes tend to sit together in a cluster in a microbe’s DNA, and they are very similar to one another. By shuffling them into different combinations, microbes can produce a staggering range of molecules.
To train the software, Dr. Fischbach and his colleagues introduced it to 732 gene clusters that are already known to make natural products. As the software examined cluster after cluster, it came to recognize distinctive patterns. Eventually the program got so good that it could accurately pinpoint new gene clusters in DNA sequences it had never encountered before. The scientists wondered what would happen if they turned their well-educated computer loose on the microbes that live in our bodies.
They provided it with a vast genetic library created in an ongoing study called the Human Microbiome Project. The project scientists have collected microbial DNA from five different body sites on 242 healthy volunteers. From that genetic material, they were able to sequence the entire genomes of 2,340 different microbial species, most of which were new to science.
Searching those genomes, the computer spotted more than 14,000 gene clusters for natural products. Dr. Fischbach and his colleagues tossed out the gene clusters that were present in only a few people. They were left with 3,118 common ones.
Their study suggests that the human microbiome is a rich source of previously unknown natural products. “That wasn’t where I expected to find interesting drug-producing genes,” said Dr. Fischbach. “I was really taken aback.”
To show the potential medical value of these genes, Dr. Fischbach and his colleagues picked out a single cluster to study more closely. It belongs a species of bacteria called Lactobacillus gasseri. They reared huge numbers of the bacteria in the laboratory in order to isolate a speck of one its products, which they dubbed lactocillin.
They found that its structure is similar to a recently discovered antibiotic called LFF571, which the drug company Novartis is now testing in clinical trials. When Dr. Fischbach and his colleagues exposed several species of bacteria to lactobacillin, the microbes died, suggesting that it might also be a good antibiotic. The idea that our own bacteria are making potent antibiotics may seem strange. If the microbiome is churning out poison, how does it avoid killing itself?
- Mining for Antibiotics, Right Under Our Noses
To train the software, Dr. Fischbach and his colleagues introduced it to 732 gene clusters that are already known to make natural products. As the software examined cluster after cluster, it came to recognize distinctive patterns. Eventually the program got so good that it could accurately pinpoint new gene clusters in DNA sequences it had never encountered before. The scientists wondered what would happen if they turned their well-educated computer loose on the microbes that live in our bodies.
They provided it with a vast genetic library created in an ongoing study called the Human Microbiome Project. The project scientists have collected microbial DNA from five different body sites on 242 healthy volunteers. From that genetic material, they were able to sequence the entire genomes of 2,340 different microbial species, most of which were new to science.
Searching those genomes, the computer spotted more than 14,000 gene clusters for natural products. Dr. Fischbach and his colleagues tossed out the gene clusters that were present in only a few people. They were left with 3,118 common ones.
Their study suggests that the human microbiome is a rich source of previously unknown natural products. “That wasn’t where I expected to find interesting drug-producing genes,” said Dr. Fischbach. “I was really taken aback.”
To show the potential medical value of these genes, Dr. Fischbach and his colleagues picked out a single cluster to study more closely. It belongs a species of bacteria called Lactobacillus gasseri. They reared huge numbers of the bacteria in the laboratory in order to isolate a speck of one its products, which they dubbed lactocillin.
They found that its structure is similar to a recently discovered antibiotic called LFF571, which the drug company Novartis is now testing in clinical trials. When Dr. Fischbach and his colleagues exposed several species of bacteria to lactobacillin, the microbes died, suggesting that it might also be a good antibiotic. The idea that our own bacteria are making potent antibiotics may seem strange. If the microbiome is churning out poison, how does it avoid killing itself?
- Mining for Antibiotics, Right Under Our Noses
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