Attacking Weaknesses in Killer Bacteria with Help from Glowing Beads

Biofilms – tightly packed sticky blobs of many bacteria – are a huge problem in the medical world. Biofilms can form on joint replacements and medical equipment, they cause long-term infections in lungs and urinary tracts, and, according to Centers for Disease Control estimates, are responsible for 1.7 million infections in U.S. hospitals every year – and 99,000 deaths.

With the rise of antibiotic-resistant bacteria, scientists are looking at new ways to attack bacterial infections and biofilms. Rather than analyzing these scourges through the lens of chemistry or genetics, biophysicist Vernita Gordon examines the mechanical properties of biofilms for potential weaknesses.

A type of infection-fighting human white blood cells, called a neutrophil, can swallow one or two bacterial cells at a time and destroy them, but biofilms can be over 10 times the size of the immune cells. Gordon, an associate professor of physics at The University of Texas at Austin, wanted to develop a way to test how different properties of biofilms affected the ability of immune cells to "bite off" small sections of the biofilms to keep them at bay.

In a recent paper in Biophysical Journal, Gordon and a team of UT Austin biologists, physicists and biomedical engineers describe a new system they devised, which uses fluorescent beads that glow when excited by a laser.

In experiments, the team developed gels to mimic different mechanical properties of biofilms and filled them with the glowing beads to represent individual bacterial cells. Then they turned the immune cells loose on the gels.

"We could look at the neutrophils after they had been exposed to the gels and see if they had [internalized] these glowing beads," said Gordon. "The only way they could get those beads was by attacking the gels."

What she discovered was that immune cells attacking softer gels had an easier time taking bites out of the simulated biofilms. On the other hand, immune cells attacking stiffer gels had a harder time.

"If we can compromise the integrity of the biofilm, we can make it easier to eat it one cell at a time," Gordon said. "Then the immune system will do a better job of clearing it out."

Having an avenue of attack against drug-resistant bacteria that goes beyond antibiotic medications is potentially very valuable in medicine.

"With a better understanding of the mechanics of these infections, we could develop treatments that don't contribute to drug resistance," Gordon said.

In addition to killing infections, a better understanding of how to aid immune cells in clearing biofilms could address a dangerous side effect of the infections. When immune cells can't get at an infection, they can enter a state where they cause inflammation in human tissues and tissue damage – a common problem for patients with cystic fibrosis, a genetic condition. Some patients even require lung transplants due to such inflammation.

"This technique is one step on the road to better understanding, and it's a valuable tool," Gordon said.

Other authors on the paper include Megan Davis-Fields, Layla A. Bakhtiari, Ziyang Lan, Kristin N. Kovach, Liyun Wang and Elizabeth M. Cosgriff-Hernandez of the University of Texas at Austin. Funding for the research was provided by grants from the Cystic Fibrosis Foundation, the National Institutes of Health, and the National Science Foundation.