before-and-after-cell-stress-80By Tina Hilding, Voiland College of Engineering & Architecture

PULLMAN, Wash. – A Washington State University research team has successfully used a mild electric current to take on and beat drug-resistant bacterial infections, a technology that may eventually be used to treat chronic wound infections.

The researchers report on their work in the online edition of npj Biofilms and Microbiomes (http://www.nature.com/articles/s41522-016-0003-0).

Led by Haluk Beyenal, the team used an antibiotic in combination with the electric current to kill all of the highly persistent Pseudomonas aeruginosa PAO1 bacteria in their samples.

These bacteria are responsible for chronic and serious infections in people with lung diseases, such as cystic fibrosis, and in chronic wounds. They also often cause pneumonia for people who are on ventilators and infections in burn victims.

“I didn’t believe it. Killing most of the persister cells was unexpected,” said Beyenal, who is the Paul Hohenschuh Distinguished Professor in WSU’s Gene and Linda Voiland School of Chemical Engineering and Bioengineering. “Then we replicated it many, many times.”

Biofilm aids antibiotic resistance

Bacterial resistance is a growing problem around the world. While antibiotics were a miracle drug of the 20th century, their widespread use has led to drug-resistant strains of bacteria. In the U.S., at least 2 million infections and 23,000 deaths are attributable to antibiotic-resistant bacteria each year, according to the U.S. Centers for Disease Control.

When doctors use antibiotics to treat a bacterial infection, many of the bacteria die. Bacteria that form a slime layer (called a biofilm), however, are more difficult to kill because antibiotics only partially penetrate this protective layer. Subpopulations of “persister” cells survive treatment and are able to grow and multiply, resulting in chronic infections.

Electronic scaffold weakens bacteria

cell-stress-web
Researchers used electric current to kill “persister” cells that cause chronic infections. The frames to the right show cells that are under stress from the e-scaffold treatment.

In the new study, the researchers used an “e-scaffold,” a sort of electronic band-aid made out of conductive carbon fabric, along with an antibiotic to specifically tackle these persister cells.

The e-scaffold creates an electrical current that produces a low and constant concentration of hydrogen peroxide, an effective disinfectant, at the e-scaffold surface. The hydrogen peroxide disrupts the biofilm matrix and damages the bacteria cell walls and DNA, which allows better antibiotic penetration and efficacy against the bacteria.

“It turns out the hydrogen peroxide is really hard on biofilms,’’ said Doug Call, a professor in WSU’s Paul G. Allen School for Global Animal Health and co-author on the paper.

Patent filed; companies express interest

Researchers have tried electrical stimulation as a method to kill bacteria for more than a century but only saw mixed results.

Beyenal’s team determined the conditions necessary for the electrochemical reaction to produce hydrogen peroxide. The current has to be carefully controlled to assure the correct reaction at an exact rate. Their method does not damage surrounding tissue, and the bacteria are unable to develop resistance.

“We pushed past the observation and got to the mechanism,’’ said Call. “If you can explain why it works, then you can move forward, describe the limitations and hopefully augment the effect.”

The researchers have filed a patent application and are working to commercialize the process. Several companies have contacted WSU to discuss commercialization. They also hope to begin conducting clinical tests.

Fuel cell failure leads to discovery

Similar to the way that penicillin was discovered by accident, the research to develop the e-scaffold came out of the Beyenal group’s failed attempt to improve fuel cells, he said. When the researchers figured out they could only produce a small amount of electric current for their fuel cell cathode, they decided to see if they could use the process for a different purpose.

“As engineers, we are always trying to find solutions to a problem, so we decided to use bad cathodes to control biofilm growth – and it worked. Our inspiration came from the fundamental work to understand its mechanism,” he said.

Along with Beyenal and Call, Sujala T. Sultana, a graduate student in the Voiland School, was a lead author on the paper. The work was supported by Beyenal’s National Science Foundation CAREER award (No. 0954186).

 

News media contacts:
Haluk Beyenal, WSU Gene and Linda Voiland School of Chemical Engineering and Bioengineering, 509-335-6607, beyenal@wsu.edu
Tina Hilding, WSU Voiland College of Engineering and Architecture communications, 509-335-5095, thilding@wsu.edu