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The author is a science commentator.
The majority of the world’s bacterial species remain invisible, as they cannot be cultivated in traditional laboratory settings.
However, scientists are now exploring ways to uncover this “bacterial dark matter.” In a recent study published in the journal Cell, an international team discovered a potential new antibiotic called clovibactin in the sandy soil of North Carolina. This compound has a unique method of killing bacteria, making it difficult for them to develop resistance. While human trials are still years away, this finding provides hope in the face of increasing drug resistance.
In 2019, drug-resistant bacterial infections directly caused the deaths of at least 1.2 million people, surpassing the mortality rates of HIV and malaria, according to The Lancet. Antimicrobial resistance (AMR) not only poses a significant public health threat but also has economic consequences. A landmark review in the UK predicted that by 2050, “superbugs” would result in 10 million annual deaths and a cumulative $100 trillion decrease in global GDP.
The postwar era was a golden age for antibiotic research, yielding compounds such as tetracyclines and vancomycin. However, progress stagnated in the 1980s due to the inability to culture the vast majority of bacterial species in the lab. Markus Weingarth, an antibiotics researcher at Utrecht University, emphasizes the importance of finding new medicines that work differently to combat drug resistance. He believes that the untapped potential lies in the remaining 99% of bacterial species, known as the bacterial dark matter.
Studying these understudied species presents challenges, as they require specific nutrients or the presence of other micro-organisms to thrive. NovoBiotic Pharmaceuticals, founded by professors Kim Lewis and Slava Epstein from Northeastern University, has been exploring this pool by collecting micro-organisms from soil samples and cultivating “domesticated” variants capable of growth in the lab. These variants are then tested for their ability to kill bacteria, including superbugs like MRSA.
The clovibactin plate demonstrated a “zone of inhibition,” indicating that the staph bacteria had been eliminated. Further studies showed its effectiveness against various bacterial infections in mice. Importantly, clovibactin utilizes a unique mechanism by targeting three different components of the bacterial cell wall, forming a deadly cage. This approach makes it challenging for bacteria to develop resistance. The compound also targets the immutable parts of the cell wall components, further reducing the chances of resistance and potentially providing a long-lasting drug. It has shown efficacy against MRSA, bacterial pneumonia, and vancomycin-resistant enterococcus. Currently, it is undergoing testing against other diseases, such as anthrax and tuberculosis.
While success is not guaranteed, clovibactin represents another potential solution in a limited pipeline of new antibiotics. NovoBiotic has previously identified teixobactin and darobactin from soil, which show promise against gram-negative bacteria such as E. coli and salmonella. These types of bacteria, resistant to multiple antibiotics, have become a significant concern in hospitals.
However, the real challenge in combating AMR lies not just in the science but also in the lack of market incentives. Developing a new antibiotic typically takes a decade and substantial funding, only for it to be used sparingly. To address this issue, innovative payment models, such as delinking payments and volume, are being explored. For instance, the NHS is experimenting with a subscription-based model known as the Pasteur bill, currently being considered by the US Congress.
It would be remarkable to imagine that with the potential solutions hiding beneath our feet, governments would prioritize funding research to address the AMR crisis. But that remains uncertain.
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