Findings from research about the role of zinc in the immune system may help the development of new non-antibiotic treatment strategies for bacterial diseases, such as urinary tract infections (UTIs), according to authors of a published study.
UTIs are one of the most common bacterial infections worldwide and can lead to serious conditions such as kidney infection and sepsis. A team of researchers examined how our immune system uses zinc to fight uropathogenic Escherichia coli (UPEC)—the major cause of UTIs.
UTIs are one of the most common bacterial infections worldwide with about 150 million cases each year, and can lead to serious conditions such as kidney infection and sepsis if not resolved.
Dr. Ronan Kapetanovic, of Queensland (AU) University Institute for Molecular Bioscience (IMB), said researchers already knew that zinc was toxic to bacteria. "We confirmed by direct visualization that cells in our immune system known as macrophages deploy zinc to clear bacterial infections," he said.
The researchers also discovered that UPEC has a two-pronged strategy to survive the body's immune response. "We found that, compared to non-pathogenic bacteria, UPEC can evade the zinc toxicity response of macrophages, but these bacteria also show enhanced resistance to the toxic effects of the zinc. These findings give us clues to how our immune system battles infections, and also potential avenues to develop treatments, such as blocking UPEC's escape from zinc to make it more sensitive to this metal,” he explained.
Kapetanovic added that treatment strategies that don't use antibiotics have the advantage of bacteria not developing resistance; “if we can reprogram our immune cells to make them stronger, or change the way they respond to bacteria, we would be better equipped to fight superbugs."
Macrophages deploy zinc toxicity against several types of bacteria, such as Mycobacterium tuberculosis, Salmonella and Streptococcus, that aren't necessarily being cleared from the body by normal mechanisms," said lead author Claudia Stocks, PhD. "We developed zinc sensors that can be adapted to study different types of bacteria, bringing us closer to understanding our immune system better and creating therapies for a range of infectious diseases."
Stocks CJ, et al. “Uropathogenic Escherichia coli employs both evasion and resistance to subvert innate immune-mediated zinc toxicity for dissemination.” Proceedings of the National Academy of Sciences, 2019; 201820870 DOI: 10.1073/pnas.1820870116