Scientists Discover Gene Cluster in Soil Bacteria with Potential Antibiotics

Researchers have pinpointed a cluster of genes within a common soil bacterium capable of producing a variety of antibiotics effective against multidrug-resistant bacteria. This finding, they suggest, could pave the way for creating antibiotics that are more resilient to bacterial resistance.

As antibiotic-resistant infections continue to escalate—forecasted to result in about 39 million deaths from 2025 to 2050—novel antibiotics with new mechanisms are urgently needed. Existing bacteria are increasingly adept at evading current treatments.

In a study published in Nature, the scientists highlight a ‘megacluster’ of genes within Streptomyces bacteria that disrupt a crucial metabolic function in bacteria. This genus of bacteria is well-studied and known for producing numerous antibiotic compounds, like streptomycin, which was the first effective treatment for tuberculosis.

Mark Blaskovich, involved in antibiotic development at the University of Queensland, remarked on the significance of this discovery. It’s intriguing to think that something so noteworthy could be overlooked in a field thoroughly examined. The gene cluster yields five compounds—four antibiotics and a protein—targeting various stages of biotin production, also known as vitamin B7, which is vital for bacterial growth. Blaskovich pointed out that since evolution has seemingly optimized this mix, there might be a chance to use it for developing new combinations of antibiotics.

Brendan Wren, a microbiologist, explained that it’s more challenging for bacteria to create resistance against antibiotics that target multiple stages of an essential metabolic pathway. The research might also uncover other gene clusters producing antibiotic compounds related to different metabolic functions.

A Long-Term Investigation

Study co-author Eric Brown, a biochemist at McMaster University, shared that he and his group have been exploring biotin metabolism as a potential antibiotic target for decades. Their work led them to the significant discovery of the mega-gene cluster. While examining stravidins, a class of antibiotics known to target biotin, they observed that the genes encoding the compounds were part of a more extensive DNA set involved in biotin synthesis. Additionally, they found genes for three other families of antibiotics: acidomycin, α-Me-KAPA, and a new group named dapamycins. The gene region also included the gene for streptavidin, a protein recognized for targeting biotin.

To validate their findings, the team cloned a section of DNA—65,808 base pairs long—holding the megacluster and inserted it into a lab strain of Streptomyces.

Brown stated that it’s unprecedented to find four biosynthetic gene clusters at a single location that produce molecules targeting the same metabolic pathway. The discovery of similar gene clusters in various Streptomyces species indicates these genetic features have been maintained throughout evolution.