Researchers have made a significant breakthrough by discovering and creating a group of molecules that fight tuberculosis in a novel manner. They explain that these new compounds, known as callyaerins, combat the infectious disease using a completely different strategy from the antibiotics currently in use.
A joint team from Heinrich Heine University Düsseldorf (HHU) and the University of Duisburg-Essen (UDE) has successfully identified and synthesized a new group of molecules that can combat the cause of tuberculosis in an innovative way. The findings have been published in the scientific journal Cell Chemical Biology, where they detail how the callyaerins function against this infectious disease using a unique approach compared to the antibiotics available so far.
Tuberculosis is caused by the bacterium Mycobacterium tuberculosis (often abbreviated as M. tuberculosis). Each year, over ten million people around the globe become infected with this disease. According to the World Health Organization (WHO), 1.6 million individuals lost their lives to tuberculosis in 2021, making it one of the most critical infectious diseases, especially in regions with poor healthcare systems where it poses a severe threat to public health.
Over the years, M. tuberculosis has become resistant to many antibiotics, complicating treatment efforts. Currently, there are only a limited number of drugs that are effective against these resistant strains. Thus, researchers are in search of new antibacterial agents and mechanisms as a foundation for creating entirely new medications.
The team, led by Professor Dr. Rainer Kalscheuer of the Institute of Pharmaceutical Biology and Biotechnology at HHU and Professor Dr. Markus Kaiser of the Center for Medical Biotechnology at UDE, has found an innovative approach involving callyaerins. These natural compounds, derived from marine sources, are categorized as cyclopeptides.
“We successfully synthesized the substance found in marine sponges to evaluate its impact on tuberculosis bacteria within cell cultures. This process allowed us to create new, more effective derivatives that are not available in nature. Successful chemical synthesis is crucial before any potential drug can be produced on a larger scale,” shares Dr. David Podlesainski from UDE, one of the lead authors of the study published in Cell Chemical Biology.
The tuberculosis bacterium mainly targets human immune cells, specifically macrophages, where it can reproduce. The research team has determined that callyaerins can inhibit the growth of the bacterium within human cells.
Emmanuel Tola Adeniyi, a Ph.D. student at HHU and co-lead author of the study, states: “The callyaerins specifically target a membrane protein of M. tuberculosis known as Rv2113, which is not crucial for the bacterium’s survival. This significantly disrupts the bacterium’s metabolism, preventing its growth, while human cells remain unharmed by the callyaerins.”
Professor Kalscheuer, the study’s corresponding author, adds: “We have identified a new mechanism of action with the callyaerins. Unlike other antibiotics that disrupt essential metabolic pathways in bacterial cells, these substances specifically attack a non-essential membrane protein of the bacterium, which has not previously been seen as a target.”
Professor Kaiser, also a corresponding author, highlights an important next step: “In our future research, we need to thoroughly investigate how callyaerins interact with Rv2113 and how this interaction affects various cellular processes, leading to the inability of M. tuberculosis to grow. Our findings suggest that non-essential proteins can also serve as valuable targets for developing new antibiotics.”
