A common ingredient in sunscreen could be an effective antibacterial coating for medical implants such as joint replacements and pacemakers. Zinc oxide nanopyramids can disrupt methicillin-resistant Staphylococcus aureus (MRSA), reducing the film of bacteria growing on coated materials by over 95%.
About one million implanted medical devices are infected each year. Treatment involves a long course of antibiotics, which can lead to antibiotic resistance or toxic side-effects. “Or the implants must be surgically replaced, which can be quite extensive for devices such as heart valves and prosthetic joints,” said J. Scott VanEpps, a clinical lecturer and research fellow in the department of emergency medicine at the University of Michigan, whose team led the biological study.
Ideally, doctors would like to prevent the infections from occurring in the first place. One option is to coat the devices with something that bacteria can’t grow on. The new results, published in the journal Nanomedicine, suggest that such a coating could be made from zinc oxide nanoparticles.
If the nanoparticles are shaped like a pyramid with a hexagonal base, they are very effective at preventing the enzyme beta-galactosidase from breaking down lactose into the smaller sugars glucose and galactose. Human cells also employ a beta-galactosidase enzyme to break down sugars for fuel, but they are not affected until a dose of nanopyramids roughly a thousand times higher than that needed to kill bacteria.
Shape is important, both for the enzymes and the nanoparticles. The enzymes need to be able to twist in order to break down the large sugar molecules. Two amino acids, or protein building blocks, sit opposite one another across a groove in the enzyme. The lactose fits into the groove, and the amino acids come together to catalyze the breakup into glucose and galactose.
The team’s research suggests that part of the nanoparticle—an edge or the point—inserts itself into the groove. By clogging up just one of the four grooves, the nanoparticles can shut down the whole enzyme by preventing the twisting action. To explore the concept of an antibacterial coating, Kotov’s group covered some pegs with the nanopyramids and then VanEpps’s team stuck them into a substance that would allow bacteria to grow. They evaluated four species of bacteria on coated and uncoated pegs—two staphylococcal species, one that causes pneumonia and E. coli.
After 24 hours of growth, the number of viable staphylococcal cells recovered from the coated pegs was 95% less than those from the uncoated pegs. The pneumonia and E. coli species were less susceptible to the nanoparticles.
Staph, including MRSA, is particularly vulnerable to the nanopyramids because its cell wall is a matrix of proteins and sugars. The team suspects that as the MRSA tried to colonize the pegs, the nanopyramids bound to the enzymes that build the cell wall. Since the enzymes couldn’t maintain the cell wall, the cells broke down. If this is indeed how the nanopyramids operate, then the coating should be no trouble for human cells, whose membrane enclosures don’t have the same vulnerabilities. It may also account for why the coating isn’t nearly as effective on E. coli, which doesn’t wear its cell wall enzymes on its sleeve.
Many hurdles stand between the nanoparticle coating and clinical use. The researchers must find out how such a coating would affect human cells near the implant. They must also explore how the nanopyramids affect other enzymes in humans and bacteria.
This work was supported by the U.S. National Science Foundation, the U.S. National Institutes of Health and the National Research Foundation of Korea and the Society for Academic Emergency Medicine.
University of Michigan Engineering