Cologne: Researchers discovered new antibiotic molecules that target Mycobacterium tuberculosis and make it less pathogenic for humans in collaboration with research partners in Germany and France. Furthermore, some of the found compounds may enable the re-treatment of tuberculosis with existing treatments, including strains of the bacterium that have already established drug resistance. The findings were published in Cell Chemical Biology as ‘Discovery of dual-active ethionamide boosters blocking the Mycobacterium tuberculosis ESX-1 secretion pathway’.
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Tuberculosis (TB) – or ‘consumption’, as it used to be called – mainly affects the lungs, but can also damage other organs. If diagnosed early and treated with antibiotics, it is curable. Although the disease is relatively rare in most western European countries, it still ranks among the infectious diseases that claim the most lives worldwide: According to the World Health Organization (WHO), only Covid-19 was deadlier than TB in 2022. The disease also caused almost twice as many deaths as HIV/AIDS. More than 10 million people continue to contract TB every year. This is mainly due to insufficient access to medical treatment in many countries.
Multidrug-resistant tuberculosis is emerging especially in eastern Europe and Asia. That is of particular concern to researchers because like all bacteria that infect humans, Mycobacterium tuberculosis possesses only a limited number of targets for conventional antibiotics. That makes it increasingly difficult to discover new antibiotic substances in research laboratories.
Working together with colleagues from the Institute Pasteur in Lille, France, and the German Center for Infection Research (DZIF), the researchers at University Hospital Cologne have now identified an alternative treatment strategy for the bacterium. The team utilized host-cell-based high-throughput methods to test the ability of molecules to stem the multiplication of bacteria in human immune cells: From a total of 10,000 molecules, this procedure allowed them to isolate a handful whose properties they scrutinized more closely in the course of the study.
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Ultimately, the researchers identified virulence blockers that utilize target structures that are fundamentally distinct from those targeted by classical antibiotics. Jan Rybniker, who heads the Translational Research Unit for Infectious Diseases at the Center for Molecular Medicine Cologne (CMMC) and initiated the study, said,
These molecules probably lead to significantly less selective pressure on the bacterium, and thus to less resistance.
In deciphering the exact mechanism of action, the researchers also discovered that some of the newly identified chemical substances are dual-active molecules. Thus, they not only attack the pathogen’s virulence factors, but also enhance the activity of monooxygenases – enzymes required for the activation of the conventional antibiotic ethionamide. Ethionamide is a drug that has been used for many decades to treat TB. It is a so-called prodrug, a substance that needs to be enzymatically activated in the bacterium to kill it. Therefore, the discovered molecules act as prodrug boosters, providing another alternative approach to the development of conventional antibiotics. In cooperation with the research team led by Professor Alain Baulard at Lille, the precise molecular mechanism of this booster effect was deciphered.
Thus, in combination with these new active substances, drugs that are already in use against tuberculosis might continue to be employed effectively in the future.
The discovery offers several attractive starting points for the development of novel and urgently needed agents against tuberculosis. “Moreover, our work is an interesting example of the diversity of pharmacologically active substances. The activity spectrum of these molecules can be modified by the smallest chemical modifications,” Rybniker added. However, according to the scientists it is still a long way to the application of the findings in humans, requiring numerous adjustments of the substances in the laboratory.
(This story has not been edited by NDTV staff and is published from a syndicated feed.)
NDTV – Dettol have been working towards a clean and healthy India since 2014 via the Banega Swachh India initiative, which in its Season 10 is helmed by Campaign Ambassador Ayushmann Khurrana. The campaign aims to highlight the inter-dependency of humans and the environment, and of humans on one another with the focus on One Health, One Planet, One Future – Leaving No One Behind. It stresses on the need to take care of, and consider, everyone’s health in India – especially vulnerable communities – the LGBTQ population, indigenous people, India’s different tribes, ethnic and linguistic minorities, people with disabilities, migrants, geographically remote populations, gender and sexual minorities. In a world post COVID-19 pandemic, the need for WASH (Water, Sanitation and Hygiene) is reaffirmed as handwashing is one of the ways to prevent Coronavirus infection and other diseases. The campaign will continue to raise awareness on the same along with focussing on the importance of nutrition and healthcare for women and children, fight malnutrition, mental well-being, self-care, science and health, adolescent health & gender awareness. Along with the health of people, the campaign has realised the need to also take care of the health of the eco-system. Our environment is fragile due to human activity, which is not only over-exploiting available resources, but also generating immense pollution as a result of using and extracting those resources. The imbalance has also led to immense biodiversity loss that has caused one of the biggest threats to human survival – climate change. It has now been described as a “code red for humanity.” The campaign will continue to cover issues like air pollution, waste management, plastic ban, manual scavenging and sanitation workers and menstrual hygiene. Banega Swasth India will also be taking forward the dream of Swasth Bharat, the campaign feels that only a Swachh or clean India where toilets are used and open defecation free (ODF) status achieved as part of the Swachh Bharat Abhiyan launched by Prime Minister Narendra Modi in 2014, can eradicate diseases like diahorrea and the country can become a Swasth or healthy India.
