Bottle-brush antibiotic busts bacterial membranes

A new antibacterial nanoparticle punches holes in bacterial cells but leaves human ones unharmed. And in a boon for combating antibiotic resistance, the nanoparticle breaks down quickly in the presence of enzymes that are abundant in the environment but absent in the human body (Biomacromolecules 2020, DOI: 10.1021/acs.biomac.0c00163).

Typically, antibiotics decompose slowly in the body and then enter wastewater treatment systems, eventually making their way into the environment. But the resulting low levels of antibiotics in these treatment plants or in waterways can drive the evolution of resistant bacteria. For this reason, experts worry about antibiotics persisting in wastewater treatment plants or in waterways.

Hongjun Liang of Texas Tech University Health Science Center and his colleagues designed the nano-antibiotic by using cellulose—an insoluble, glucose-based macromolecule—as the spine of a brush. To this backbone, they linked many positively charged polymer strands to form the bristles.

Bacteria have negatively charged surface membranes that tend to wrap around the nanoparticles, tearing the microbes open in the process. Tests showed that the nanoparticles effectively killed clinical multi-drug-resistant strains of Pseudomonas aeruginosa and Staphylococcus aureus. Then, when treated with cellulase, an enzyme that breaks down cellulose, the antimicrobial nanoparticles disintegrated and stopped working. “Having this very specific trigger to break the molecule down enables more precise control,” says materials science researcher Edmund F. Palermo of Rensselaer Polytechnic Institute, who was not involved with the study. “It’s a big advantage relative to letting the antibacterial degrade on its own.”

Unlike many antibiotics, which tend to be specific for either gram-positive or gram-negative microbes, the nanoparticles can be designed to be effective against both simply by tuning the size of the nanoparticle, Liang says. The nanoparticles were nontoxic to cultured human cells and didn’t appear to break red blood cells apart.

In future studies, the researchers will need to test the nanoparticles in animal models of bacterial infections, and verify that they degrade in real-world environments such as wastewater. The nanoparticles’ size or charge may need to be optimized for different applications, Palermo says. Nonetheless, the results “put a lot of the bottle-brush chemistry of such polymers in a new light,” he adds. Using such structures as antibacterial polymers “is novel and can start inspiring people to think about this architecture as a platform for antibacterial compounds.”