Researchers from the University of Sydney and Centenary Research Institute have discovered how a promising class of experimental antibiotics could destroy the bacteria that causes tuberculosis (TB), paving the way for urgently needed new treatments.
Globally, tuberculosis remains a major health crisis, claiming approximately 1.2 million lives each year and ranking as one of the world’s deadliest infectious diseases. The increase in drug-resistant strains, including in the Asia-Pacific region, makes the search for new therapeutic strategies increasingly urgent.
In a study published in nature communicationsThe research team investigated how three natural antibiotic compounds, ecumicin, iramycin, and cyclomarin, act on important protein breakdown machinery in the body. Mycobacterium tuberculosisthe bacteria that causes tuberculosis.
A molecular machine known as the ClpC1-ClpP1P2 complex allows bacteria to degrade damaged or unnecessary proteins, allowing them to withstand stress and maintain essential functions. Without it, Mycobacterium tuberculosis cannot survive, making it an attractive drug target.
Co-senior author Professor Warwick Britton, laboratory director in the Centenary Institute’s Center for Infection and Immunity, said the study revealed surprising complexity in how the three antibiotic compounds affect this system.
“Mycobacterium tuberculosis relies on this decomposition system to stay alive, especially under stressful conditions within the human body,” Professor Britton said.
“Our findings show that these compounds don’t just shut down the system. Rather, each interferes with the system in different ways, causing widespread imbalances throughout the bacteria. This disruption weakens the bacteria’s ability to function and survive.”
Lead author Isabel Barter, a PhD candidate at the University of Sydney, who also carried out part of the study at Centenary Research Institute, said they measured changes in more than 3000 proteins. Mycobacterium tuberculosis.
“By tracking changes across a large portion of the bacterial protein network, we were able to see how disrupting a single essential complex reshapes the entire bacterial internal protein landscape,” she said.
“This deeper understanding will provide valuable insight into how to purify these compounds and design more precise and effective anti-tuberculosis treatments.”
Co-senior author Professor Richard Payne from the University of Sydney said the ClpC1-ClpP1P2 complex was a promising but still relatively understudied drug target.
“Our study highlights the possibility of directly targeting this proteolytic system,” Professor Payne said. “Understanding how different compounds interact and disrupt their normal functions will allow us to more strategically design the next generation of anti-tuberculosis drugs.”
The research team believes this study is an important step toward expanding the pipeline of potential new treatment options for tuberculosis, including drug-resistant forms.
[ENDS]
Publication:
Peptide natural products targeting ClpC1 specifically dysregulate the M. tuberculosis proteome
https://www.nature.com/articles/s41467-026-68423-2
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