“The stocks of new bioactive compounds in nature have certainly not dried up yet.”

In a report from the World Health Organization some years ago, scientists stated that “antibiotic resistance has risen dangerously in all parts of the world.” This means that antibiotic resistance and the growing number of people with infections pose an increasingly serious global threat to our health. The demand for new types of antibiotics is therefore increasing sharply. Researchers are therefore constantly scrutinizing new microbes in order to fully characterize them. And a new analysis shows we shouldn’t lose hope of solving antibiotic resistance.

jet fungi

In the search for new drug candidates, researchers studied a soil microbe known as Lentzea flaviverrucosa† †L. flaviverrucosa is a member of a large and diverse group of related bacteria, the ray fungi,” said study researcher Joshua Blodgett in conversation with Scientias.nl from. “Practically speaking, this group includes some very beneficial organisms (such as the streptomycetes, which produce many life-saving antibiotics and other drugs), as well as some notoriously bad ones (such as mycobacterium, which can cause tuberculosis and leprosy).”

Ray fungi are known to produce some bioactive components, which are the basis for many clinically useful drugs, especially antibiotics and anticancer drugs. Since the 1940s, pharmaceutical companies have analyzed common ray fungi to see what they produce. Today, about two-thirds of all antibiotics used in hospitals and clinics are derived in part from ray fungi.

Some of the microbes that can be categorized as jet agarics — known as the rare jet agarics — have been catalogued, but have not been extensively studied until now. And Lentzea flaviverrucosa is one such. “It Lentzeagender wasn’t formally recognized until the mid-1990s, so they’re not very well studied yet,” Blodgett said. “We do know that Lentzea is more closely related to the benign streptomycetes mentioned earlier, although it still differs considerably from them. These organisms are believed to be primarily bottom dwellers.”

Striking appearance

While the definition of ‘rare’ is not set in stone, the microbes that are known to be so are generally more difficult to find in nature than others. In addition, they grow more slowly. And both of these may have contributed to the fact that many rare ray fungi have not yet been fully characterized. “Among the rare ray fungi came Lentzea flaviverrucosa however, as a standout,” said Blodgett. “It has unusual biology, codes for unusual enzymes and stimulates the production of unexpected chemistry.”

Cancer

As the researchers dug further, they stumbled upon a pleasant surprise. It turns out that Lentzea flaviverrucosa actually produces two different bioactive molecules from a single set of genes called a supercluster. And superclusters, which are scarce in biology. In addition, it appears that the molecules produced by the rare microbe are active against certain types of human ovarian cancer, fibrosarcoma, prostate cancer and leukemia. “The approach we used was perfectly suited for antibiotic discovery,” Blodgett explains. “But our tests instead led us in the direction of cancer cells. This is not mutually exclusive, however. Some really important drugs for cancer and immunotherapy were originally discovered as antifungal antibiotics and were later developed to treat other diseases.”

Antibiotic resistance

So it means that scientists have discovered a potential new candidate for drug development. The study also shows that rare ray fungi are an untapped source of new bioactive compounds. And that offers hope in the fight against antibiotic resistance. “The fact that we have encountered such an interesting array of new bioactive compounds from a rare ray fungus underlines that new molecular discoveries await within overlooked or unusual groups of bacteria,” Blodgett said. “And that is promising for our search for new antibiotics. It shows that the stocks of new bioactive compounds in nature have certainly not dried up yet.”

Clinical Applications

Incidentally, it is still too early to say whether the molecules that Lentzea flaviverrucosa produces – and are active against various types of cancer – will have clinical applications. “The fact that we have discovered such activities is very promising,” Blodgett says. “We are therefore enthusiastic, but do not exaggerate. In terms of drug development, there are still many steps to be taken.”

What the study does show is that nature is an important source of inspiration for the discovery and design of new medicines. And that’s an important lesson for our search for new antibiotics: we don’t have to give up the fight just yet. As regards Lentzea flaviverrucosa, the researchers now plan to further map the promising molecules. “We’re actually just beginning to characterize them and study whether they have other activities against different cell types and organisms,” Blodgett says. “I’m sure there’s more to be found there…”