Recently graduated Iowa State University doctoral student Logan Ott, microbiology, and senior Chloe Smith, biochemistry, with associate professor Melha Mellata in her microbiology lab.
AMES, Iowa – A research team at Iowa State University has found that zinc supplements may be an inexpensive, effective antidote to the growing health threat of antimicrobial resistance, potentially extending the effectiveness of today’s antibiotic arsenal against disease.
Infections from bacteria resistant to antibiotics are a growing threat to human health. Several million people in the United States are diagnosed with antimicrobial-resistant (AMR) infections every year. By 2050, it is predicted that around 2 million people — the majority aged 70 and over — could die from drug resistant infections annually, according to a 2024 report in the journal Nature.
Antimicrobial resistance can spread from bacteria to bacteria through circular genetic material called plasmids. This transfer is exacerbated in the gut, where billions of microbes live close to each other. When bacteria transfer AMR genes, they can transfer resistance to multiple drugs.
“This means a person can develop a resistant infection even before they receive antibiotics,” said Melha Mellata, associate professor of molecular microbiology at Iowa State. “Stopping the transfer of plasmids could dramatically slow the spread of AMR genes.”
In a lab-based experiment, students working with Mellata were able to significantly reduce the transfer of AMR-carrying plasmids by applying a zinc solution to normal human gut bacteria exposed to avian pathogenic Escherichia coli that contained a multi-drug-resistant plasmid. They created the zinc formulations from off-the-shelf zinc supplements.
Their findings, published this month in Applied and Environmental Microbiology, are spurring widespread interest. The lead author of the article, Logan Ott, completed his doctoral degree in microbiology this summer.
The idea originated with an assignment Mellata and Ott gave undergraduate honors students, inspired by her recent studies that found short-chain fatty acids could reduce antimicrobial resistance in bacteria. In an attempt to find out if other dietary compounds could have a similar effect, Mellata and Ott tasked the students with identifying a list to investigate.
The students each did background research and selected dietary supplements of interest to study, with a goal of looking for any potential impact on plasmid transfer among gut bacteria. They ran hundreds of tests of various compounds. Chloe Smith, a senior honors student in biochemistry, proposed to evaluate zinc. It wasn't long before she saw a sharp drop in bacterial colonies on the test plates with the zinc supplement. The group tried more reactions and realized she was on to something.
"It was a lot like looking for a needle in a haystack," Mellata said, “but she found one!”
The team retested with different zinc concentrations and dug in to further analyze what might be happening. Zinc wasn’t necessarily the most likely supplement to have this result. Some earlier work by others had suggested similar elements could have an opposite effect and boost genes responsible for plasmid transfer.
Ott and Smith also found this general trend, yet the plasmid transfer between bacteria was still significantly reduced. After more research, the team detected that the expression of the plasmid transfer genes was affected by zinc, disrupting the transmission process.
While higher doses of zinc showed the biggest impact, lower concentrations also reduced plasmid transfer. “This finding is important, too,” Mellata said, “since at lower concentrations, the zinc can be expected to have minimal effect on the beneficial bacteria that also live in the gut.”
The researchers emphasize that further studies in live animal models are the next steps needed to verify their findings.
Ott, who will start a postdoctoral research assistant position this year at the University of Denver, praised Smith for her “very structured, deliberate work throughout the project, including evaluating the experimental approach and analyzing the data.”
Smith said the project has been exciting and has encouraged her interest in attending medical school after graduation. In the meantime, she is engaged in new research in Mellata's lab.
“This important work reflects two years with many steps to put this all together and solve a complex puzzle,” Mellata said. “It happened thanks to outstanding, passionate students who kept asking and answering questions.”
Funding for the project included USDA Hatch support for the College of Agriculture and Life Sciences, graduate student research support from the USDA-National Institute for Food and Agriculture and National Science Foundation, and an ISU Honors Undergraduate Research Program grant.
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