Researchers have discovered the human microbiome – the collection of microorganisms that live in and on our bodies – contains over 3,000 clusters of bacterial genes with blueprints for building cellular factories that make drug-like molecules. In a study published in Cell, they reveal how one gene cluster from bacteria that live in the vagina codes for enzymes capable of making an antibiotic called lactocillin.
The traditional view of how antibiotics come about is drug companies develop them, the federal authorities approve them, doctors prescribe them, and then we take them to overcome the bugs they are designed to tackle.
But this new study reveals a surprising alternative scenario: bacteria in and on our bodies are already busy creating tiny factories that make antibiotics just as powerful and capable of targeting specific pathogens as the ones made by pharmaceutical companies.
One of the most remarkable biological discoveries of recent times is the human microbiome, the trillions of microbes that live in and on the human body. As they continue to explore and better understand it, scientists have come to realize the human microbiome is not random and plays a role in many basic life processes.
While researchers have long known bacteria live in and on the human body, traditional microbiology has typically focused on individual species, and regarded them as isolated, culturable units. But recent advances in technologies like DNA sequencing have revealed a different picture – that species of microbes live as communities that have evolved intimately with their hosts over millions of years.
Our bacteria are involved in a wide range of metabolic and developmental processes, from food digestion to vitamin synthesis. Recently, scientists have even suggested the gut microbiome may offer clues about autism.
Now in this latest study, the researchers suggest the human microbiome may be a rich source of naturally occurring drugs for protecting health.
Senior author Michael Fischbach, assistant professor of bioengineering in the School of Pharmacy at the University of California San Francisco, says while scientists have discovered that disease appears to arise when microbiome species diversity and abundance differs from the normal range, the identification of molecules that control interactions between the bacteria and the host cells has lagged behind, and so far we are only aware of a handful of these.
In a way, it should not be surprising that our microbiomes make drugs. Prof. Fischbach, who specializes in discovering interesting molecules made by microbes, says around a third of all the drugs we use come from microbes and plants. These include antibiotics like penicillin, many chemotherapy drugs, and drugs for lowering cholesterol.
In their study, he and his colleagues purified and solved the structure of lactocillin, an antibiotic compound that is produced by a common bacterial species, Lactobacillus gasseri, found in microbial colonies in the vagina.
Lactocillin is closely related to antibiotics that pharmaceutical companies are already testing. It kills several bacteria that infect the vagina, while leaving harmless microbes intact.
In their study the team made use of an algorithm they developed called ClusterFinder to identify clusters of bacterial genes that are switched on in a coordinated way to guide the production of molecules that are biologically active in humans.
When they used it to systematically analyze genomes from microbiome species and data on gene activity from human samples, they identified 3,118 distinct clusters of bacterial genes that are found in various parts of the human body.
The gene clusters they identified encode enzymes that produce drug-like molecules that fit into known classes of drugs produced by drug companies.
They also found that the level of analysis used to identify bacteria within human microbiomes is not detailed enough to reveal specifically which molecules are made by which bacteria. Different species make different molecules, and even strains within each species differ in the molecules they produce, says Prof. Fischbach, who explains:
“We need to learn what these molecules are and what they are doing. This could represent a pool of molecules with many tantalizing candidates for drug therapy. It’s been clear for several years that variations and changes in the human microbiome have interesting effects on the human host, and now we can begin to determine why this is true on a molecular level.”