New bacterial ‘dark matter’ offers hope for a drug-resistant world
The writer is a science commentator
Just as most of the energy and matter in the cosmos is invisible, most of the world’s bacterial species go unseen because they cannot be conventionally grown in the lab.
Now scientists are finding ways to sift through this so-called bacterial “dark matter”. On Tuesday, an international team announced in the journal Cell that they had identified a potential new antibiotic lurking unnoticed in the sandy soil of North Carolina. The compound, called clovibactin, employs an unusual method of killing bacteria that makes it tough for targets to develop resistance. While clinical trials in humans are several years away, the finding is a glimmer of hope in an increasingly drug-resistant world.
According to The Lancet, at least 1.2mn people died as a direct result of drug-resistant bacterial infections in 2019, more than from HIV or malaria. The phenomenon of antimicrobial resistance (AMR) — in which infections become untreatable as pathogens evolve resistance to drugs — is not just a public health challenge but a drain on the economy. A landmark 2016 UK review predicted that, by 2050, “superbugs” would kill 10mn a year and cumulatively cut world gross domestic product by $100tn.
The postwar years were the heyday of antibiotic research, yielding such compounds from soil bacteria as tetracyclines, a class of broad-spectrum antibiotics, from the 1940s, and vancomycin in the 1950s. But, with only about 1 per cent of bacterial species culturable in the lab, progress began stalling in the 1980s.
That stasis gave microbes the evolutionary upper hand. As Markus Weingarth, an antibiotics researcher at Utrecht University and co-author on the Cell paper, explains, battling drug resistance depends on finding new medicines that work in different ways: “Most antibiotics are derived from natural products and there may be really novel molecules waiting for us in the other 99 per cent, this bacterial dark matter.”
These understudied species are demanding; they require special nutrients, for example, or the presence of other micro-organisms to thrive. NovoBiotic Pharmaceuticals, founded by professors Kim Lewis and Slava Epstein from Northeastern University in Boston, has been tapping into that pool by collecting micro-organisms from soil samples, mimicking their natural environment in specially designed chambers, and so cultivating “domesticated” variants capable of growing in the lab. These variants are then screened for bug-killing properties, by being placed on plates with the bacteria Staphylococcus aureus (MRSA, a strain resistant to the antibiotic methicillin, is one of the most-feared superbugs).
The clovibactin plate showed a tell-tale “zone of inhibition”, where the staph bacteria had died off. Subsequent studies showed it could also clear several different bacterial infections in mice. Critically, Weingarth, together with colleagues at the University of Bonn, found it displayed an unusual modus operandi: latching on to three different components used to build the bacterial cell wall and essentially forming a deadly cage (its name derives from klouvi, meaning cage in Greek).
That three-pronged attack, Weingarth explains, makes it tough for a bacterium to evolve resistance. Clovibactin also targets the immutable parts of those wall components, additionally lowering the chances of resistance and potentially providing a drug with a long shelf-life. According to the company, the compound is effective in the lab against MRSA, bacterial pneumonia and vancomycin-resistant enterococcus; it is now being tested against other diseases, including anthrax and tuberculosis.
Success is by no means assured, but it is at least another candidate in a relatively empty pipeline. NovoBiotic has also previously identified teixobactin and darobactin from soil. The latter shows promise against “gram-negative” bacteria such as E. coli and salmonella, which have an additional protective membrane. MDR-GNB, or multi-drug resistant gram-negative bacteria, has become a grimly familiar acronym in hospitals.
The real AMR challenge, though, is perhaps not the science but the lack of market incentive. It takes at least a decade and perhaps a billion dollars to bring a new antibiotic to market — which must then be used only sparingly. The NHS is experimenting with delinking payments and volume; the Pasteur bill, currently with the US Congress, is floating a similar subscription-based model.
It would be wonderful to think that, with all those potential superbug slayers under our feet, someone, somewhere is going to hit AMR pay dirt. But that does presuppose governments being prepared to pay for the dirt.
This story originally appeared on: Financial Times - Author:Anjana Ahuja
