Corramycin, a natural antibacterial compound derived from myxobacterial extracts, effectively targets resistant strains of Mycobacterium tuberculosis by attacking bacterial DNA-gyrase in a novel manner, according to a study published in the journal Advanced Science. Researchers from the Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), the Institut Pasteur, Université Paris Cité, and the German Center for Infection Research (DZIF) found that the compound overcomes fluoroquinolone resistance, offering a potential new pathway for treating drug-resistant tuberculosis.
Screening Microbial Extracts for Tuberculosis
The research originated from a screening program evaluating an extensive library of myxobacterial extracts against the tuberculosis pathogen, Mycobacterium tuberculosis. Corramycin emerged from this process as a strong candidate. Laboratory testing demonstrated that the natural compound acts against various forms of the tuberculosis bacterium, including clinical samples already resistant to standard antibiotics. These findings suggest the substance could succeed where established treatments fail. The project reflects collaborative research efforts between HIPS—a site of the Helmholtz Centre for Infection Research in cooperation with Saarland University—and international partners, including teams led by Dr. Stéphanie Petrella at the Institut Pasteur and Université Paris Cité, alongside DZIF research groups headed by Prof. Jan Rybniker at the University Hospital Cologne and Prof. Norbert Reiling at the Research Center Borstel, Leibniz Lung Center.
Mechanism of Action Against DNA-Gyrase
While previous work established Corramycin as an antibiotic agent, the latest research demonstrates its specific activity against Mycobacterium tuberculosis and clarifies its cellular mechanism. Dr. Franziska Fries, a scientist in the Microbial Natural Products department at HIPS, noted that Corramycin targets DNA-gyrase—an essential enzyme bacteria need to replicate their genetic material—differently than fluoroquinolones, which are clinically utilized antibiotics that also bind to DNA-gyrase. This distinct binding profile accounts for why Corramycin remains effective against fluoroquinolone-resistant bacteria. Cryo-electron microscopy allowed the team to visualize how Corramycin binds to DNA-gyrase. The natural compound not only inhibits the enzyme but forces it into a state that damages the bacterium itself. Specifically, Corramycin binds to the gyrase after it has cut the DNA, preventing the enzyme from rejoining the DNA strands. This disruption causes severe genomic damage, leading to bacterial cell death.
Prior Development and Next Steps
Corramycin was evaluated previously in a development program alongside Sanofi/Evotec, focusing on gram-negative bacteria responsible for urinary tract infections. Despite its recognized pharmaceutical potential, that initial development was discontinued due to high production costs. The newly discovered activity against Mycobacterium tuberculosis provides grounds to reevaluate the compound under different circumstances. Prof. Rolf Müller, Scientific Director of HIPS and head of Microbial Natural Products, stated that while the results present a promising starting point for developing new treatments against resistant tuberculosis, substantial hurdles remain. Before the substance can become a clinical drug, researchers must optimize its production methods, verify its activity within the human body, and refine its pharmacokinetic properties.
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