Synthetic polymers could be the silver bullet for multidrug-resistant superbugs

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Targeting drug-resistant bacteria with synthetic polymers is not a new idea, but it has run into challenges, such as toxicity and a limited ability to target multiple strains of bacteria. (Steve Buissinne)

Drug-resistant bacteria are on the rise and could soon outpace our capacity to develop new antibiotics. An international team is trying to head this off with synthetic molecules to treat multiple superbugs.

The team, from IBM Research and Singapore’s Institute of Bioengineering and Nanotechnology (IBN), created a new class of synthetic polymers targeting five deadly drug-resistant bacteria. Although this approach is not new, others who have tried it have hit some roadblocks, such as non-biodegradability, which could lead to a toxic buildup of polymer in the body. Some polymers had trouble targeting multiple strains of bacteria, wrote James Hedrick of IBM Research in a blog post.

The IBM-made polymers, called guanidinium-functionalized polycarbonates, work by binding to a bacterial cell and then being transported across the cell membrane into the cytoplasm. Once inside the cell, they cause the precipitation—or deposition in solid form—of cell contents, such as proteins and genes, which ends up killing the bacterial cell.

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The researchers tested the drug in mice infected with five different superbugs, including E. coli and methicillin-resistant Staphylococcus aureus (MRSA), as well as in mice with systemic infections. The treatment eliminated the bacteria from the mice and effectively treated the infections with “negligible” to no toxicity. The findings appear in Nature Communications.

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Superbugs kill about 700,000 people each year, according (PDF) to the Review on Antimicrobial Resistance. This could increase to 10 million people each year if superbugs keep developing resistance. They are already starting to beat last-line antibiotics, polymyxins, which are only given to patients infected with drug-resistant bacteria.

Some researchers are looking for new antibiotics or working to improve existing ones. A Rutgers University-led team discovered a new antibiotic produced by a microbe found in Italian soil that could be useful against bacteria that have become resistant to the antibiotic rifampin. And scientists at the University of Queensland re-engineered the antibiotic vancomycin, finding it has the potential to fight MRSA and vancomycin-resistant Enterococci (VRE).

A Rockefeller University team created an entirely new type of molecule, dubbed “lysibodies,” which are hybrids of human antibodies and lysins, which bind to carbohydrates on cell walls. These human-germ hybrids attach to bacterial cells and trigger an immune response to destroy the bacteria. And Canadian researchers are working to cripple a pathway that supplies energy to more than 20 types of pathogenic bacteria.

A genomic analysis performed by the IBM team showed that the bacteria did not develop resistance to their polymers, even after multiple treatments. The scientists are now looking for pharma partnerships to develop the polymers into an antimicrobial treatment.