A research team at the University of Arizona College of Medicine – Tucson is developing a drug that works in combination with copper to kill bacteria, including those that cause MRSA, a type of staph infection that is resistant to usual treatments. They published their results last month in mSphere .
MRSA is caused by methicillin-resistant Staphylococcus aureus, which is classified as a serious threat by the Centers for Disease Control and Prevention and a high-priority pathogen by the World Health Organization .
"It likes to live on our skin – about 30% of people are colonized with it. It becomes a problem when it gets in a wound, where it can wreak havoc," said Michael D. L. Johnson, an associate professor of immunobiology and senior author of the paper.
While MRSA can be treated with other antibiotics, bacteria's ability to evolve drug resistance means finding novel treatments is crucial.
"History has shown us that bacteria have an exquisite ability to adapt to their surroundings," Johnson said. "The more tools we have in our toolkit, the better prepared we will be to fight the next threat."
MRSA can be spread by skin-to-skin contact and appear as a painful boil. It can also occur in a hospital setting, where it might colonize a surgical wound or be introduced to the body through tubing, such as a catheter, or an implant, such as an artificial joint.
"People who are diabetic are very susceptible to staph infections, specifically in wounds they may develop," Johnson said. "It also binds to plastic really well. Can you guess where there's a lot of plastic? In a hospital. We've become quite reliant on plastic, which creates a niche for that microbe."
The team also looked at a cousin of MSRA, Staphylococcus epidermidis, which is usually harmless but can cause infections in hospitals due to its affinity for plastic. Both MSRA and S. epidermidis adhere to plastic by producing a "glue" called biofilm.
"That stuff you feel on your teeth when you wake up in the morning – that's biofilm," Johnson said. "Bacteria make biofilm to hold on to host cells or surfaces, and that biofilm is a protective shield from the bacteria's environment – such as antibiotics or antimicrobial peptides our bodies make."
Supported by funding from Tech Launch Arizona , the Johnson Lab designed the platform for a molecule called BMDC, short for N-benzyl-N-methyldithiocarbamate, to work with copper, based on a similar molecule they studied previously . TLA provided the funds through its Asset Development Program, which provides support to move potentially impactful innovations closer to readiness for commercialization and real-world impact.
"This one actually worked better than our original compound, DMDC, which killed different Streptococcusspecies – but not staph," Johnson said.
He says BMDC works by disguising itself as iron, a nutrient that hungry bacteria scavenge from their surroundings. But instead of iron, the compound contains a toxic dose of copper.
"Our compound mimics specialized molecules that carry iron. The staph bacteria are like, 'Oh, sweet, iron! This is my lucky day!' They unlock the compound, and, oops, it's copper," he explained. "Our compound is a Trojan horse, intoxicating bacteria with copper, killing them within the biofilm. The bacteria don't learn from their mistakes, and they do it over and over again."
Working with TLA, Johnson has filed a patent application on the technology, and they are searching for a company to license the product to develop it further. Their plan is to take it to clinical trials in humans, which they hope will lead to FDA approval to treat MRSA and other infections.
In the meantime, the Johnson Lab is preparing to launch a collaboration with the Department of Surgery's Division Chief of Pediatric Surgery Kenneth W. Liechty, to conduct additional laboratory experiments to see if their compound helps with wound infections and healing.
"How amazing would it be if someday, we could put some of our stuff on an open wound with a bad infection, and the infection got better?" said Johnson, who is also a member of the BIO5 Institute . "We're very interested in the translation of our discoveries to the clinic, and you don't do that unless you're partnered with amazing people here at U of A to do those experiments."
Johnson says the possibility that his work in the lab could someday benefit humanity is profoundly inspiring.
"Those are the things basic science and translational researchers dream about," he said. "It makes the science more exciting when you can see the application at the end of the road."
This research is supported in part by the National Institute of General Medical Sciences, a division of the National Institutes of Health, under award No. 2R35128653.
