A US-based team of researchers has found a new candidate for treating tuberculosis.
While the potential treatment has only been currently shown to work in a lab, making it years away from patient use, it uses a new mechanism to defeat the drug-resistant pathogen.
Tuberculosis kills 1.5 million people a year: it’s second only to COVID in lethal infectious diseases.
Currently, the standard way to treat it involves four different antimicrobial drugs, taken over six months.
These target the tuberculosis-causing bacteria, Mycobacterium tuberculosis.
But the rise of antibiotic resistance is making it harder and harder to use these drugs: tuberculosis bacteria become resistant, particularly if the patient doesn’t finish the full course, and the drugs can also affect other bacteria in someone’s body.
This has spurred the search for other compounds that could take out tuberculosis.
A study published in Nature Chemical Biology has landed on a substance, isolated from another bacteria, that can destroy M. tuberculosis.
The compound, called evybactin by the researchers, targets tuberculosis bacteria specifically.
Evybactin comes from a bacteria called Photorhabdus noenieputensis, which lives in nematodes.
“Microorganisms such as actinomycetes and filamentous fungi have long been used as a source of antibiotics,” says first author Yu Imai, assistant professor at the Institute for Biomedical Sciences at Shinshu University, Japan, who did the research at the Antimicrobial Discovery Center, Northeastern University US.
Imai says in recent years, it has become difficult to find new antibiotics from these microorganisms, as known substances have been re-isolated.
“Recently, we have succeeded in discovering several antibiotics from the nematode symbiotic bacterium Photorhabdus,and have shown that this bacterium is a useful source for the discovery of new antibiotics.”
The researchers took a number of cultures from Photorhabdus, and tested them against M. tuberculosis and another bacteria, S. aureus, to test their specificity.
“We used this method, called differential screening, [that] allows us to eliminate antibiotics that may exhibit broad-spectrum or cytotoxic activity in the early stages of screening,” says Imai.
“Thus, differential screening is an excellent method for finding antibiotics that exhibit species-specific activity.”
They found that evybactin could target M. tuberculosis specifically.
They also figured out the mechanism behind evybactin’s destruction of tuberculosis: how it gets carried inside the cell and binds up a key enzyme in tuberculosis bacteria.
It’s the first time this antimicrobial mechanism has been observed.
Before it becomes the next big tuberculosis drug, evybactin will need to go through animal and then human clinical trials – a process that will take several years.
“For accelerated development as an antituberculosis drug, it is necessary to evaluate the safety, pharmacokinetics and long-term administration of evybactin to M. tuberculosis patients,” says Imai.
Still, even if this specific compound doesn’t work, the researchers now have a better method for finding new antimicrobial drugs.
“In this study, we demonstrated that it is possible to find new antibiotics by using relatively untouched microorganisms as a search source for useful antibiotics,” says Imai.
Ellen Phiddian is a science journalist at Cosmos. She has a BSc (Honours) in chemistry and science communication, and an MSc in science communication, both from the Australian National University.
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