New mAb Disrupts Bacterial Biofilms

Temple University researchers have found a therapeutic molecule that can break apart biofilms, opening the way for bacteria-killing antibiotics to more effectively clear out infections. Biofilms are notorious for forming on implanted medical devices and on tissues in the body, where they give rise to chronic and sometimes life-threatening infections. Biofilms are extremely difficult to eradicate, because, united with an impermeable matrix, the microbes are able to resist antibiotics and other agents that would otherwise eliminate them.

The new monoclonal antibody, however, has been shown to open up these biofilms, causing their dissociation. It is the first agent of its kind to show promise as an immunotherapeutic strategy to fight off infectious biofilms, according to the Temple team.

"With this new antibody, we open the door for better treatment strategies for patients who suffer from chronic infections associated with implanted medical devices or who suffer from recurrent infections, such as repeated infections of the urinary tract," explained Cagla Tukel, Ph.D., senior author on the study published last week in Nature Communications.

The new antibody, named 3H3, was isolated from a healthy human subject by Scott K. Dessain, M.D., Ph.D., coauthor on the study. Drs. Dessain and Tukel were intrigued by 3H3's ability to attach to beta-amyloid. A form of amyloid called curli is secreted by bacterial cells and is a major component of biofilms. Bacterial amyloid curli acts like glue, enabling bacterial cells to adhere to one another and form a continuous film over a surface.

In experiments with biofilms of infectious Salmonella enterica serovar Typhimurium, which forms biofilms in the human intestinal tract and on medical devices, the team found that amyloid binding by 3H3 disrupted biofilm formation, causing the separation of bacterial cells within the biofilm. The researchers then tested the antibody in mice infected with catheter-associated S. Typhimurium biofilm. In these animals, 3H3 injections also led to biofilm dissociation and, when followed by antibiotic therapy, allowed for the swift eradication of individual bacterial cells from the animals.

There are currently no existing therapies that are used clinically to break up biofilms. Here Dr. Tukel's team showed that while 3H3 breaks the biofilm, it also prevented the dissociating bacteria from entering the circulation, where they could cause sepsis. 3H3 was found to bind to individual bacterial cells facilitating their uptake by immune cells. Therefore, this novel approach has the potential to also reduce the risk of sepsis.