Researchers at the Texas A&M College of Veterinary Medicine and Biomedical Sciences (VMBS) are investigating how the body utilizes copper as a defense against urinary tract infections (UTIs), particularly against bacteria that have become resistant to antibiotics. The study, backed by a $1.48 million grant from the National Institutes of Health (NIH), builds on previous work by Dr. Sarguru Subash, an associate professor in the VMBS Department of Veterinary Pathobiology, who found that copper levels rise in the urinary tract during infections to help combat invading bacteria.
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Copper serves dual roles; while it is essential in small amounts for humans and animals, it becomes toxic to bacteria under certain conditions. The immune system exploits this toxicity as part of its innate response to infection. During UTIs, specialized immune cells engulf bacteria and expose them to a mix of antimicrobial substances, including copper, which also increases in urine, as noted in Dr. Subash's earlier findings.
Despite this, many bacteria have developed mechanisms to resist copper's effects. The research will focus on understanding the genetic systems that enable UTI-causing bacteria to tolerate increased copper levels, allowing them to thrive even in its presence. "If we better understand how the bacteria overcome the host's copper resistance, then we can develop therapies to make the bacteria more vulnerable to copper and the immune system's defenses," stated Subash.
The team is also looking into evidence suggesting that copper may disrupt fimbriae, the hairlike structures bacteria use to attach to bladder cells. Weakening this attachment could help flush out bacteria more effectively, as attachment is essential for bacterial survival in the urinary tract.
Additionally, the effectiveness of copper in combating UTIs is influenced by other immune strategies. "Bacteria do have adaptations, but in conjunction with this cocktail of defenses, their protective mechanisms can be challenged," Subash explained. The researchers will also focus on ceruloplasmin, a copper-carrying protein that may aid copper delivery during infections. Managing copper levels is critical since high concentrations can harm the body’s own cells.
Through this combined approach, researchers aim to gain insights into both copper delivery and bacterial resistance, potentially leading to treatments that enhance the body’s natural defenses. The laboratory has already identified a compound that increases in effectiveness when copper is present, with plans to test related compounds compatible with the immune response.
Subash mentioned that while a clinical application for copper-based treatment may be several years away, this project marks an important step toward developing alternatives for treating complex UTIs. Discoveries related to how bacteria withstand copper could also extend to other bacterial infections and even veterinary medicine, where UTIs are common in animals. Ultimately, the goal is to connect scientific understanding of both pathogens and host defenses to foster potential new treatment strategies.