The search for new and potentially potent therapeutic molecules in nature is a vital quest spurred on by parallel health crises: antibacterial resistance and the growing global cancer burden.
A team of scientists has discovered that a rare soil microbe produces some strange yet familiar building blocks with drug-like activity. Drug design and discovery programs could benefit from this.
Joshua Blodgett, a microbiologist at Washington University in St. Louis, is the senior author of the new study.
The focus of their exploration was a group of spindly, soil-dwellingbacteria called actinomycetes, which are prolific producers of medical compounds.
Once thought to be largely devoid of new drugs, the team discovered a deep trove of yet-undiscovered drug-like molecules hidden in actinobacterial genomes.
The building blocks for more than 50 percent of antibiotics used today in clinics and hospitals are found in actinomycetes.
The global health threat of antimicrobial resistance, which is spawning drug-resistant faster than new drugs can be produced, has led to a renewed interest in exploring actinomycetes as rich sources of bioactive molecule.
In the search for new drug candidates, Blodgett, Lia and colleagues turned their attention to a rare actinomycete, which was found in China and goes by the name of Lentzea flaviverrucosa.
It is more difficult to find in nature than other actinomycetes and it is harder to grow in the lab. The researchers found it to be quite odd.
It has unusual biology, driving the production of unexpected chemistry, all harbored within a largely overlooked group ofbacteria.
The team had tried to find out if L. flaviverrucosa could make small, circular molecule called piperazyl molecule, which are useful scaffolds for synthesizing drugs.
The researchers discovered that L. flaviverrucosa produces two types of piperazyl molecule. The compounds were different because they were produced by a single set of genes.
At a high level, it looked as if one region of the genome might be able to make two different molecules.
Usually, we think of a gene cluster as groups of genes that are like blueprints for making individual drug-like molecules. It looked like there was too much chemistry predicted.
The researchers realized that one of the compounds was unlike anything they had ever described before. When tested against certain types of human cancer cell lines, the asymmetrical duo had potential drug-like activity.
Blodgett explains that nature is welding two different things together.
Drug testing on lab-grown cell lines is not the same as treatment in a clinical trial. It takes decades for potential drug candidates to make their way from the lab to the clinic, and many fail in the process.
Ursula Theuretzbacher, an independent antibacterial drug expert, and colleagues wrote that much more work, focus and funding are needed for the novel approaches to result in effective antibacterial therapies.
The hope is that with more analyses like this one, which seek to identify which strains hold the most promise and which compounds are most likely to succeed, researchers are on the right track.
The research was published in a journal.
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