Scientists at the University of California-San Francisco have purified an antibiotic they named lactocillin, which is made by a common bacterial species (Lactobacillus gasseri) found in the microbial community within the vagina. Lactocillin kills several vaginal bacterial pathogens, but spares species known to harmlessly dwell in the vagina. The antibiotic is closely related to others already being tested clinically by pharmaceutical companies as potential new human therapeutics.
The researchers published their finding (“Systematic Analysis of Biosynthetic Gene Clusters in the Human Microbiome Reveals a Common Family of Antibiotics”) in Cell.
Michael Fischbach, Ph.D., an assistant professor of bioengineering with the UCSF School of Pharmacy and senior author of the study, thinks this example suggests that there may be an important role for many naturally occurring drugs made by our own microbes in maintaining human health.
“We used to think that drugs were developed by drug companies, approved by the FDA, and prescribed by physicians, but we now think there are many drugs of equal potency and specificity being produced by the human microbiota,” said Dr. Fischbach, adding that about a third of all medicines used in the clinic are derived from microbes and plants. These include antibiotics like penicillin, numerous drugs used in cancer chemotherapy, and cholesterol-lowering drugs.
There are hundreds of bacterial species associated with each of us, and thousands of distinct strains among them. We do not all harbor the same species, and different species are found at different body sites.
Scientists have started to identify microbiomes in which species diversity and abundance differ from the normal range in ways that are associated with disease risks. However, the identification of molecules that govern interactions between microbes and their human hosts has lagged; only a handful have been identified, according to Dr. Fischbach.
By developing new data-analysis software and putting it to work on an extensive genetic database developed from human-associated bacterial samples collected as part of the ongoing Human Microbiome Project, Dr. Fischbach’s lab team identified biosynthetic gene clusters (BCGs) that are switched-on in a coordinated way to guide the production of molecules such as lactocillin that are biologically active in humans.
“We demonstrate that lactocillin has potent antibacterial activity against a range of Gram-positive vaginal pathogens, and we show that lactocillin and other thiopeptide BGCs are expressed in vivo by analyzing human metatranscriptomic sequencing data,” wrote the investigators. “Our findings illustrate the widespread distribution of small molecule-encoding BGCs in the human microbiome, and they demonstrate the bacterial production of drug-like molecules in humans.”
“We need to learn what these molecules are and what they are doing,” explained Dr. Fischbach. “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.”