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Antibiotic resistance poses a significant challenge to public health. While there are few new compounds in the pipeline, a promising newcomer, clovibactin, has emerged. This antibiotic, derived from previously unexplored bacteria, demonstrates potential in combating multidrug-resistant “superbugs” through unique mechanisms of action.
Researchers from Utrecht University (Netherlands), the University of Bonn (Germany), the German Center for Infection Research, Northeastern University (Boston), and NovoBiotic Pharmaceuticals (Cambridge, Massachusetts) collaborated on this breakthrough, which was published in the journal Cell.
Markus Weingarth, MD, PhD, a researcher at Utrecht University’s chemistry department, noted, “Since clovibactin was isolated from bacteria that couldn’t be cultivated previously, pathogenic bacteria hadn’t encountered such an antibiotic before, leaving them no opportunity to develop resistance.”
Utilizing the iCHip device, developed in 2015, researchers isolated clovibactin from sandy soil in North Carolina. This innovative technique allowed for the cultivation of “bacterial dark matter,” a group encompassing 99% of bacteria, including previously unculturable strains. This device also played a pivotal role in the discovery of the antibiotic teixobactin in 2020, which, like clovibactin, targets gram-positive bacteria.
In their Cell article, the researchers demonstrated that clovibactin operates through multiple mechanisms, successfully treating mice infected with the superbug Staphylococcus aureus. It exhibited efficacy against various gram-positive pathogens, including drug-resistant strains of S. aureus and vancomycin-resistant Enterococcus faecalis and E. faecium. Escherichia coli was minimally affected, likely due to limited penetration of the compound.
What sets clovibactin apart is its unique mechanism of action, binding to three crucial molecules involved in bacterial wall construction. By encasing its targets in a “cage-like” structure, clovibactin effectively hinders bacterial resistance. This binding leads to the formation of stable fibrils on bacterial membranes, ensuring prolonged sequestration of target molecules for effective bacteria elimination.
Due to its specific mode of action, clovibactin is anticipated to have minimal side effects, as it selectively targets bacterial cells without affecting human cells. However, further studies, especially in humans, are necessary before considering it a potential treatment. Meanwhile, strict antibiotic usage regulations remain crucial to combat antibiotic resistance.
In 2019, approximately 4.95 million deaths worldwide were linked to bacterial antimicrobial resistance, including 1.27 million directly attributable to it. Without the introduction of new antibiotics, it is estimated that by 2050, antimicrobial resistance could lead to an annual toll of 10 million lives lost.
