The more often antibiotics are used, the higher the probability that pathogens will become resistant to the active substances used. In the case of tuberculosis in particular, such antimicrobial resistance plays an enormously important role, as several active substances have to be used over a period of up to six months during treatment in order to successfully combat the stubborn pathogen. In Europe, the proportion of resistant tuberculosis pathogens is already 20 percent on average, and in some regions of Africa or Asia it is significantly higher. Worldwide, around 1.3 million people die of tuberculosis every year, while the figure for malaria, a disease transmitted by mosquitoes, is around 600,000. New resistance-breaking agents are urgently needed to prevent this situation from worsening and to ensure that both infectious diseases can continue to be treated successfully in the future. Researchers at the HIPS are working on this task together with Evotec as part of a project funded by the Bill & Melinda Gates Foundation. The HIPS is a site of the Helmholtz Centre for Infection Research (HZI) in collaboration with Saarland University. The HIPS is also involved in numerous projects of the German Center for Infection Research (DZIF). As coordinator of the research area "New Antibiotics", Prof. Rolf Müller also plays an important interface role in the DZIF for the development of new active substances.
As part of the project, the researchers want to further develop previously identified drug candidates that can be used to treat the two infectious diseases tuberculosis and malaria – especially if the pathogens are already resistant to commonly used drugs. The basis for this are substances that are produced by soil bacteria to combat competing microbes. "When searching for new active substances, we focus exclusively on molecules that have previously unused modes of action. In this way, we avoid a new drug being limited in its effectiveness by resistance mechanisms that are already widespread," says Jennifer Herrmann, Team Leader Biology in the Department of Microbial Natural Products at HIPS. "With effective substances against both tuberculosis and malaria in our portfolio, we now want to optimize these in the project so that they can ultimately be used safely in human therapy."
Established drug candidates from previous screening programs will be further profiled using Evotec's established platforms. A droplet microfluidics-based screening model enables the identification of new microbial natural products and their use for the development of new antibiotics.
Collaboration between public research institutions and the pharmaceutical industry seems obvious, but is a rarity in the field of antibiotics research. "Most large pharmaceutical companies have stopped developing new antibiotics over the past ten years for economic reasons. Nevertheless, we see it as our responsibility to continue working on this topic, as new active substances are urgently needed. With support from the Gates Foundation, we are pleased to foster close collaboration between academic research and the pharmaceutical industry in this important field," said Dr. Cord Dohrmann, Chief Scientific Officer of Evotec.
In addition to receiving funding from the Gates Foundation, HIPS has also been accepted as a member of the Tuberculosis Drug Accelerator. This is a partnership of leading research institutions and pharmaceutical companies, also coordinated by the foundation, which are developing new strategies and active compounds against tuberculosis. "The funding provided by the Gates Foundation will enable us to significantly advance some of our most promising development projects and take important steps towards potential application. Becoming a member of the Tuberculosis Drug Accelerator also gives us direct access to leading experts and technologies that will be invaluable along the way," says Rolf Müller, Managing Director of HIPS and Head of the Department of Microbial Natural Products. "The current developments will also create valuable synergies for the HIPS research projects based at the DZIF." Evotec has been a member of the Tuberculosis Drug Accelerator since 2018.
The three-year research project between HIPS and Evotec was scheduled to start in January 2024, with funding amounting to around 3.1 million euros.
