Drug-Resistant Tuberculosis

New Antibiotic Molecules Discovered for Treating Drug-Resistant Tuberculosis


Researchers have made a significant breakthrough in the treatment of tuberculosis (TB), one of the deadliest infectious diseases worldwide. In a recent study published in Cell Chemical Biology, scientists have identified new antibiotic molecules that target Mycobacterium tuberculosis, the bacterium causing TB, and make it less harmful to humans. These substances also have the potential to enable the renewed treatment of TB with existing medications, even in cases where the bacterium has developed drug resistance.

TB, also known as consumption, primarily affects the lungs but can also cause damage to other organs. If diagnosed early and treated with antibiotics, the disease is curable. However, TB remains a major public health challenge, resulting in millions of deaths each year. In fact, according to the World Health Organization (WHO), TB was the second deadliest infectious disease in 2022, surpassed only by COVID-19. Moreover, TB caused almost twice as many deaths as HIV/AIDS. Insufficient access to medical treatment in many countries is a major contributing factor to the high number of TB cases worldwide.

The emergence of multidrug-resistant TB, particularly in eastern Europe and Asia, has raised concerns among researchers. Mycobacterium tuberculosis has limited targets for conventional antibiotics, making it increasingly difficult to discover new antibiotic substances in laboratories.

To address this challenge, researchers from the University Hospital Cologne, the Institute Pasteur in Lille, France, and the German Center for Infection Research (DZIF) collaborated to develop an alternative treatment strategy for TB. Using host-cell-based high-throughput methods, the team screened 10,000 molecules to identify those that could inhibit the growth of bacteria in human immune cells. Through this process, they isolated a few molecules that were further analyzed during the study. These molecules, known as virulence blockers, targeted structures that differed from conventional antibiotic targets, minimizing selective pressure on the bacterium and reducing the likelihood of resistance.

In addition to identifying virulence blockers, the researchers discovered that some of these newly identified substances were dual-active molecules. They not only targeted the bacterium’s virulence factors but also enhanced the activity of enzymes required for the activation of the conventional antibiotic ethionamide. Ethionamide has been widely used to treat TB for several decades, and the discovery of these dual-active molecules expands the potential of this drug.

The research team, in collaboration with Professor Alain Baulard’s team at Lille, deciphered the precise molecular mechanism of this booster effect. By combining these new active substances with existing drugs used against TB, more effective treatment options may be available in the future.

This groundbreaking discovery provides promising avenues for the development of novel agents against tuberculosis, addressing the urgent need for new treatments. The researchers also highlight the diverse range of pharmacologically active substances, with the potential to modify the activity spectrum through small chemical modifications.

While significant progress has been made, it is important to note that applying these findings in humans is still a long-term goal. Further adjustments and testing of the substances in the laboratory are necessary before clinical trials can be conducted. Nonetheless, this breakthrough brings hope for a more effective treatment approach against drug-resistant tuberculosis, potentially saving millions of lives globally.

1. Source: Coherent Market Insights, Public sources, Desk research
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