A New Polymer Reverses Antibiotic Resistance and Boosts Existing Antibiotics

By Katia Moskvitch

IBM researchers have created a new molecule able to fight antibiotic resistance. By modifying the pathogens biomacromolecules (seen right), the molecule allows drugs to reach their target and work as intended.

ntibiotic resistance crisis could start easing soon — thanks to a new a macromolecule polymer created at an IBM Research lab.

Antibiotic resistance is the adaptive ability of pathogens to defend themselves against drugs made to fight them. This ability has evolved because of the misuse and over-use of antibiotics over the last several decades, and it kills some 700,000 people globally every year.

Dr. James Hedrick, material scientist at IBM Research in Almaden

The new polymer boosts the effectiveness of existing antibiotic treatments against increasingly resistant bacteria, write the researchers in a paper recently published in Advanced Science.

The results “can be broadly applied across many diseases and used to address the emergence of stronger strains of bacterial infections,” says the lead author, material scientist James Hedrick at IBM Research in Almaden in the US. It can fight, for instance, the ESCAPE pathogens responsible for hospital acquired infections, he says. Such infections are on the rise because of the lack of new drugs and because antibiotic resistance is happening more and more often.

Typically, such resistance develops if sublethal doses of a drug are used to eradicate a pathogen. This allows the bacteria to evolve to elude the drug, which generally involves chemical modification of the drug or its target with internal biomacromolecules (enzymes, proteins or genes), making the drug useless. But the new polymer, when used with specific existing FDA-approved drugs, reverses antibiotic resistance — a potentially huge breakthrough that could add decades to existing therapeutics.

The researchers combined the polymer with the anti-tuberculosis drug rifampicin and the antirheumatic drug auranofin, and repurposed them to become very effective against Gram-negative bacteria A. baumannii. Such combination approach is often used to develop more efficient ways to treat a disease. But it typically involves a lengthy trial-and-error process, somewhat dependent on luck. Instead, the polymer the team has designed addresses the very root of the problem of antibiotic resistance — the biomolecules within the bacteria that modify the drug or its target.

To do that, the researchers spent a decade studying antimicrobial polymers, together with a team in Singapore’s Institute of Bioengineering and Nanotechnology. The polymer they’ve created overcomes antibiotic resistance phenotypes and enhances the effectiveness of the antibiotic. It attaches itself to the so-called cytosolic enzymes (biological molecules) that bacteria alter when treated with antibiotics. This is why it’s important to take the full course of antibiotics — if the pathogen isn’t eliminated completely, it may develop resistance to the treatment.

The polymer enables antibiotics that have garnered resistance to harmful pathogens to become active again. “Our polymer interacts with these evolved biomolecules to allow the antibiotic to work as intended,” says Hedrick.

Before the polymer is brought to the market, it would have to undergo clinical trials. But Hedrick’s team’s next step, though, is to broaden the approach to address the wider problem of chemotherapeutic resistance. “Typical cancer treatments require taking many drugs because of this resistance. We aim to reduce the amount of drugs and design therapies that will prevent resistance from developing in the first place.”

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