New Molecule Shows Promise In Eradicating Infectious Biofilms

Wally

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https://www.sciencedaily.com/releases/2020/02/200227114507.htm
New immunotherapeutic strategy shows promise in eradicating infectious biofilms
Date: February 27, 2020
Source: Temple University Health System
Summary: The same way baking soda breaks down grease and grime, making surfaces easier to clean, researchers now show that a new therapeutic molecule can break apart communities of harmful bacteria, opening the way for bacteria-killing antibiotics to more effectively clear out infections.

The same way baking soda breaks down grease and grime, making surfaces easier to clean, researchers at the Lewis Katz School of Medicine at Temple University (LKSOM) now show that a new therapeutic molecule can break apart communities of harmful bacteria, opening the way for bacteria-killing antibiotics to more effectively clear out infections.

Communities of bacteria known as biofilms are notorious for forming on implanted medical devices, such as catheters and prosthetics, and on tissues in the body, where they give rise to chronic and sometimes life-threatening infections in patients. 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 molecule, a type of monoclonal antibody, however, is able 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.

The new antibody, named 3H3, was isolated from a healthy human subject . . . .Drs. . . . were intrigued by 3H3's ability to attach to beta-amyloid, a sticky protein that functions abnormally in Alzheimer's disease. 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. . . .

There are currently no existing therapies that are used clinically to break up biofilms.

. . . [W]hile 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 reduce the risk of sepsis.

"We are very excited about these findings," Dr. Tukel said. "There is great need for an immunotherapy that can be used alongside lower dose antibiotics or other antimicrobials to safely and effectively eradicate biofilms in infectious settings."

Dr. Tukel and colleagues plan next to test 3H3 on a wide variety of biofilms. As many important pathogenic bacteria produce curli or curli-like amyloids in their biofilms, such as Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa, this novel immunotherapy has the potential to be applied to a wide variety of infections.

"We also are developing a clinical approach," Dr. Tukel noted. "Our preclinical findings in animals are promising, and we've identified a clear path to clinical development." . . .

See, Salmonella Typhimurium biofilm disruption by a human antibody that binds a pan-amyloid epitope on curli. Nature Communications, 2020; 11 (1) DOI: 10.1038/s41467-020-14685-3