Molecular Tweezers Found To Attack Antibiotic-Resistant Bacteria

June 16, 2021

By Deborah Borfitz

June 16, 2021 | An international team of researchers has come up with a new application for “molecular tweezers” originally developed to untangle the amyloid nanofibers found in the brain of patients with Alzheimer’s and Parkinson’s disease. As it turns out, the tiny synthetic molecules may also be a way to prevent and treat bacterial infections like Staphylococcus aureus that have grown resistant to antibiotics, according to Raz Jelinek, a professor in the department of chemistry at Ben-Gurion University (Israel).

As recently described in a paper published in Cell Chemical Biology (DOI: 10.1016/j.chembiol.2021.03.013), the tweezers were found to be highly effective in both preventing S. aureus bacteria from constructing a protective biofilm, and also in tearing apart the tiny network of fibers forming the biofilm once it had already been built. The results, based on mouse blood and serum samples, suggest that the tweezers may be potent biofilm inhibitors and antibacterial agents, Jelinek says.

The novel strategy targets biofilms that bacteria build around themselves once they reach a certain population threshold, he explains. This protective shield is stable, resilient, and impenetrable by chemicals the immune system uses to fight off pathogens and is part of the reason bacterial infections can be dangerous if not lethal.

Shielded by biofilms, bacteria can quickly multiply and start wreaking havoc in the body, says Jelinek. But biofilms form gradually and intervening early in the process ups the odds of evading infection.

The clinical potential is untrivial. In the U.S., S. aureus infections have an estimated mortality rate of over 25%—up to 40% when a drug-resistant strain is the culprit, he says.  

Since many other types of bacteria have similar biofilm fiber structures, the tweezers may have broad applicability as an anti-infective agent, Jelinek says, although that assumption still needs to be tested. The tweezers, first synthesized a decade ago by researchers in the U.S. and Germany, have already been shown to inhibit abnormal protein aggregation and attracted a lot of interest among drug developers in pursuing the approach as a treatment for Alzheimer’s disease.

Jelinek says he hopes his current line of research will lead to a marketable treatment, possibly a pill containing millions of "swallowable tweezers" that could identify bacteria-affiliated biofilms in the body and break them apart. Other possibilities are to administer the tweezers through the bloodstream or directly to places in the body where bacteria are congregating, he adds.

A patent related to the molecular tweezers is owned by researchers from the University of California, Los Angeles, and the University of Duisburg-Essen (Germany), some of whom were co-authors on the Cell Chemical Biology study.