New way to harness copper makes antibiotic-resistant bacteria and cancer cells more vulnerable

This article has been reviewed according to Science X's editorial process and policies . Editors have highlighted the following attributes while ensuring the content's credibility: A computer-generated visualization shows a compound, MKV3, connected to a protein in the human body that transports copper. Credit: Michael Petris University of Missouri researchers have discovered a new way to harness one of the body's natural defenses: copper. While copper is essential for life and helps power important biological processes, having too much of it can be toxic. To keep copper levels in balance, cells rely on specialized proteins that regulate where it goes and how much is present. In a new study published in the Proceedings of the National Academy of Sciences, the Mizzou team identified the first compound, called MKV3, that blocks a key type of copper transport protein, disrupting both the delivery of copper to enzymes that require it and the export of excess copper from cells. "Copper is already one of the immune system's natural defenses," said Michael Petris, professor of biochemistry in Mizzou's School of Medicine and the College of Agriculture, Food and Natural Resources, a principal investigator in Mizzou's Christopher S. Bond Life Sciences Center and senior author of the study. "What we've done is find a way to make cancer cells and microbes more vulnerable to it." MKV3 was initially identified by Kamal Singh, an assistant professor of veterinary pathobiology in Mizzou's College of Veterinary Medicine, a principal investigator in the Bond Life Sciences Center and co-author of the study. He used computer modeling to help design the drug candidate. Then the team tested it in the lab to confirm that it worked as expected and studied its properties in more detail. MKV3 could open the door to new approaches for fighting antibiotic-resistant infections and developing treatments that target cancer cells. Potential new treatments for infections and cancer Many pathogenic bacteria depend on this copper-export system during infection. When the human immune system attacks invading microbes, it uses high levels of copper as a natural defense. Bacteria fight back by pumping excess copper out of their cells. The Mizzou team found that MKV3 inhibits these copper export pumps, making bacteria more vulnerable to the toxic effects of copper. For example, in laboratory tests, MKV3 made MRSA—one of the most difficult antibiotic-resistant bacteria to treat—significantly more susceptible to copper. "Antibiotic resistance continues to be a major global health challenge," Petris said. "Our findings suggest that targeting copper transport could become an entirely new strategy for helping the body fight infections." The discovery could also have important implications for cancer research because copper metabolism is emerging as a potential target in cancer. By blocking copper transport, MKV3 attacks this metabolic dependence in two ways. "In cultured cancer cells, it caused copper to accumulate, increasing sensitivity to cuproptosis, a form of cell death caused by copper," said Vinit Shanbhag, an assistant research professor in the College of Veterinary Medicine, a principal investigator in the Bond Life Sciences Center and the study's lead author. "At the same time, MKV3 reduced the activity of lysyl oxidase by limiting copper delivery to this enzyme, which is linked to tumor invasion and metastasis. Together, these findings support further investigation of MKV3 as a potential strategy for cancer treatment." Discover the latest in science, tech, and space with over 100,000 subscribers who rely on Phys.org for daily insights. Sign up for our free newsletter and get updates on breakthroughs, innovations, and research that matter—daily or weekly. A discovery that spans the tree of life The discovery reaches well beyond human health. Researchers demonstrated that MKV3 affects copper transport proteins not only in mammals but also in fungi, plants, fish and disease-causing microbes. "What makes this discovery especially powerful is that MKV3 targets a pocket that is conserved in copper transporters across organisms separated by millions of years of evolution," Shanbhag said. "For the first time, researchers have a chemical tool to probe the same fundamental transport mechanism in bacteria, fungi, plants and animals, allowing discoveries in one system to inform work in another." MKV3 remains an early-stage discovery that will require additional testing before it could be considered for any medical applications. But researchers say identifying the first compound capable of targeting this fundamental copper transport system establishes a foundation for future discoveries in medicine, agriculture and basic biology. Publication details Vinit C. Shanbhag et al, A broad-spectrum inhibitor of copper-exporting P 1B -type ATPases, Proceedings of the National Academy of Sciences (2026). DOI: 10.1073/pnas.2604078123 Journal information: Proceedings of the National Academy of Sciences