In a study published this week in the journal Advanced Science, researchers detail polymers they claim are effective against antibiotic-resistant bacteria. For this project, IBM researchers teamed up with scientists from the Agency for Science, Technology and Research and the Singapore-MIT Alliance for Research and Technology. The researchers say their technique enabled them to generate up to 100 bacteria-fighting polymers in nine minutes. They believe these polymers could be combined with other therapeutics to make them more effective.
Antibiotics have transformed the world of medicine over the past century or so, but they’ve also been misused, leading to the emergence of bacteria with powerful resistance. “Gram-negative” pathogens, which include E. coli, salmonella, and those that cause pneumonia, tuberculosis, and sepsis, pose a particular challenge because their outer membranes can protect them from antibiotics like penicillin. Amid a surge in drug-resistance infections, the World Health Organization (WHO) has identified gram-negative pathogens as a “critical priority.”
Combination therapy has attracted attention as a method of treating multidrug-resistant (MDR) bacteria, with studies showing biodegradable polymers called broad-spectrum antimicrobial guanidinium-functionalized polycarbonates can “modestly” improve outcomes in conjunction with anti-tuberculosis and anti-rheumatic drugs. Inspired by this, the IBM researchers and their colleagues designed a process for testing and exploring a range of polymers for increasing antibiotic strength, iterating until the most effective polymer was identified.
Typically brought on by “sublethal” drug doses, antibiotic resistance develops when bacteria modify enzymes, proteins, or genes. The researchers’ polymer appears to prevent this by attaching to the modifying enzymes, enabling drugs to bypass protective measures and take effect. It also seems to reduce required dosages to levels equal to or below amounts used for weaker strains, suggesting it can strengthen drugs to fight more serious (and potentially lethal) infections.
For example, in an experiment with the MDR a. baumannii, which can cause infections in the blood, urinary tract, and lungs, the coauthors say the presence of the polymer improved the effectiveness of the drugs azithromycin, gentamicin, imipenem, tetracycline, and colistin. In a separate experiment, the polymer enabled the team to repurpose the anti-tuberculosis and anti-rheumatic drugs rifampicin and auranofin — which are normally not effective against gram-negative bacteria — to fight a. baumannii with “strong potency.” The rifampicin therapy in particular seemed to accelerate bacterial death by stressing the cytosol, the intracellular fluid within the cells.
“Going forward, we will seek to leverage the knowledge gained in this study, our prior work in automated, programmatic polymer synthesis, … and IBM’s AI capabilities to rapidly develop novel polymeric adjuvants. Applications of these new treatments can potentially range from treating drug-resistant pathogens and cancer to new antiviral therapies,” the researchers wrote in a blog post. “The global crisis of antibiotic resistance continues to grow at an alarming pace. In the absence of a new class of stronger antibiotic drugs to help curb the consequences of this resistance, applying therapeutic combination approaches such as those published in our research could hold significant potential for fighting MDR gram-negative bacterial infections.”