Much of the achievements of modern medicine can be attributed to antibiotics, without which even routine surgery can quickly turn into a life-threatening infection. However, drug-resistant bacteria are beginning to evolve, threatening to undo decades of progress in global health, particularly for diseases like tuberculosis.
Instead of targeting specific bacterial proteins, antimicrobial peptides kill bacteria by targeting their negatively charged cell membrane. Scientists have mimicked this effect using positively charged polymers called polyionenes, which insert themselves into the bacteria membrane. “Polyionenes destabilize the phospholipid bilayer so that the bacteria have no chance to develop resistance,” explained Yi Yan Yang, Covering Executive Director of A*STAR’s Institute of Bioengineering and Nanotechnology (IBN).
In a finding that addresses the challenge of antibiotic resistance while recycling plastic waste at the same time, Yang and her team have developed a simple chemical process to turn one of the most common plastics into bacteria-killing polyionenes.
The team first broke polyethylene terephthalate (PET) down into three different monomers, using an inexpensive process that did not require catalysts or solvents. They then built up a library of potential polyionenes synthesized using different combinations of monomers, selecting those that were able to kill bacteria cells while leaving human red blood cells intact.
“We found that the hydrophobic-hydrophilic balance of the polymers ensures that we have the best in terms of antimicrobial activity and selectivity towards microbes over mammalian cells,” Yang said.
One of the resulting polyionenes was even able to kill Mycobacterium avium, which, like the closely related M. tuberculosis bacteria, is difficult to treat because it resides inside the host cell. “The polyionenes might enter the mammalian cell by diffusion before eliminating the intracellular microorganisms based on the membrane-disruption mechanism,” Yang said.
“From our studies, repeated treatment of bacteria over many passages using the polyionenes at sub-lethal doses did not increase the effective concentration of the polyionenes. In contrast, multiple treatments with antibiotics significantly increased their effective concentration,” Yang said.
The researchers have filed for a patent on their process, which effectively turns plastic waste into a potent antimicrobial. This study is part of an ongoing collaboration with James Hedrick from the IBM Almaden Research Center.
“We are not only recycling the PETs, but upcycling them into antimicrobial products,” added Yang. “In the future, we hope they can be used as disinfectants for the prevention of bacterial infections.”
The A*STAR-affiliated researchers contributing to this research are from the A*STAR Institute of Bioengineering and Nanotechnology (IBN).