Bacteria are at least as much of a threat to each other as they are to us, and the chemical warfare among them gets lethal. The molecules they use as weapons are an obvious resource in the quest to create new antibiotics. Unfortunately, the armed bacteria have been holding out on us, hiding many chemicals that could provide the next generation of antibiotics. One team think they’ve found a way around that.
If there’s one lesson to take from the pandemic, it’s to act early before infectious diseases get away from us. The slow-growing crisis of antibiotic resistance could prove the most important example, making scandalous the limited number of drugs under development to tackle bacteria that have developed resistance to existing drugs.
Actinobacteria are already the source of some of the most widely used antibiotics, such as streptomycin and actinomycin. However, it’s known these are just a small sample of what they produce.
“In laboratory conditions, bacteria don’t make the number of molecules they have the capability of making,” said Professor Satish Nair, of the University of Illinois at Urbana-Champaign, in a statement. “And that’s because many are regulated by small-molecule hormones that aren’t produced unless the bacteria are under threat.”
Avenolide is a hormone known to play an important role in the production of some actinobacteria’s anti-parasitic chemicals, but it has been difficult to synthesize. One of Nair’s graduate students Iti Kapoor has improved the methods for producing avenolide using an efficient 22-step process (which the team call “concise”), giving the lab enough to study its effects.
In eLife, Nair and Kapoor report avenolide binds to a receptor. In the hormone’s absence, the receptor binds instead to the DNA of its own bacterium, blocking the organism’s production of defensive chemicals. Adding avenolide turns production back on. So, problem solved? Just add avenolide and watch the actinobacteria pour out next-generation antibiotics? Not so fast, there are many different species of actinobacteria, and the team have identified 90 that have similar but slightly different receptors. They expect some these can be blocked with avenolide, verifying in two cases, but anticipate others require related hormones.
“Our long-term project is to take those 90 bacteria, grow them up in the laboratory, add chemically synthesized hormones to them and see what new molecules are being produced,” Nair said.
If the team can match the right hormone to the actinobacteria species, the potential rewards are immense. Genes for the production of 300,000 molecules thought to serve as weapons against other bacteria are known to exist in the Streptomyces genus alone. Many will prove unsuitable for treating human diseases, for example because they harm us as much as the pathogens we are trying to kill. If even a small proportion serve our needs, however, they could save millions of lives.
