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Düsseldorf and Duisburg, August 1, 2024 — Researchers from Heinrich Heine University Düsseldorf (HHU) and the University of Duisburg-Essen (UDE) have made a significant breakthrough in the fight against tuberculosis (TB) by identifying and synthesizing a novel group of molecules that target the disease in a fundamentally new way. Their findings, published in the scientific journal Cell Chemical Biology, introduce callyaerins—a promising class of molecules that offer a new approach to combating TB.
Tuberculosis, caused by the bacterium Mycobacterium tuberculosis (M. tuberculosis), continues to be a global health challenge, infecting over ten million people annually. The World Health Organization (WHO) reported 1.6 million TB-related deaths in 2021, underscoring the severity of this infectious disease. In many parts of the world, particularly in regions with limited healthcare resources, TB poses a significant threat. The rise of antibiotic-resistant strains has further complicated treatment, with only a handful of effective drugs available for resistant cases.
In response to this urgent need for new treatment options, a research team led by Professor Dr. Rainer Kalscheuer from HHU’s Institute of Pharmaceutical Biology and Biotechnology and Professor Dr. Markus Kaiser from UDE’s Center of Medical Biotechnology has explored a novel approach using callyaerins. These natural compounds, derived from marine sponges, are chemically classified as cyclopeptides.
Dr. David Podlesainski, a lead author of the study from UDE, explained, “We have successfully synthesized callyaerins in the lab, enabling us to test their effects on TB bacteria in cell cultures. This synthesis has allowed us to create new, more potent derivatives that are not found in nature. Such chemical advancements are crucial before these compounds can be developed into large-scale drugs.”
The researchers discovered that callyaerins effectively inhibit the growth of M. tuberculosis within human macrophages, the primary host cells for the bacteria. Emmanuel Tola Adeniyi, a doctoral researcher at HHU and co-lead author of the study, noted, “Callyaerins target a specific membrane protein in M. tuberculosis called Rv2113. Although Rv2113 is not essential for the bacterium’s survival, its disruption significantly hampers bacterial metabolism and growth, without affecting human cells.”
Professor Kalscheuer emphasized the significance of this discovery: “Callyaerins introduce a new mechanism of action. Unlike traditional antibiotics that block essential metabolic pathways, these substances target a non-essential protein in the bacterium, presenting a novel strategy for antibiotic development.”
Professor Kaiser added, “Further research is needed to fully understand how callyaerins interact with Rv2113 and disrupt bacterial processes. However, our findings highlight that non-essential proteins can be valuable targets for developing innovative antibiotics.”
This breakthrough offers renewed hope in the quest for effective TB treatments, particularly in the face of rising drug resistance. The development of callyaerins could mark a significant advancement in TB therapy, potentially paving the way for new, more effective treatments in the future.
