Certain polymers have antibacterial capabilities, which means they can kill or limit the growth of germs. Scientists have developed a new class of polymers capable of killing bacteria without causing antibiotic resistance – a significant step forward in the fight against superbugs such as E. coli and MRSA.
Antibiotic-resistant bacteria are posing an increasing hazard to public health. According to the Centers for Disease Control and Prevention, they cause more than 2.8 million infections each year. Even minor injuries and illnesses can become fatal in the absence of new antibiotics.
Scientists are one step closer to eradicating that threat, owing to a Texas A&M University-led team that has produced a novel family of polymers capable of killing bacteria without inducing antibiotic resistance by breaking the membrane of these germs.
“The new polymers we synthesized could help fight antibiotic resistance in the future by providing antibacterial molecules that operate through a mechanism against which bacteria do not seem to develop resistance,” said Dr. Quentin Michaudel, assistant professor in the Department of Chemistry and lead investigator in the study, which was published in the Proceedings of the National Academy of Sciences (PNAS).
A common issue with antibacterial polymers is a lack of selectivity between bacteria and human cells when targeting the cellular membrane. The key is to strike a right balance between effectively inhibiting bacteria growth and killing several types of cells indiscriminately.
Dr. Quentin Michaudel
The Michaudel Laboratory was able to synthesize the new polymer by carefully designing a positively charged molecule that can be stitched many times to form a large molecule made of the same repeating charged motif, using a carefully selected catalyst called AquaMet. According to Michaudel, the catalyst is critical since it must tolerate a high concentration of charges while still being water-soluble – a quality he describes as unusual for this type of operation.
After achieving success, the Michaudel Lab put its polymers to the test against two main types of antibiotic-resistant bacteria – E. coli and Staphylococcus aureus (MRSA) – in collaboration with Dr. Jessica Schiffman’s group at the University of Massachusetts Amherst. While awaiting those results, the researchers also tested their polymers’ toxicity against human red blood cells.
“A common issue with antibacterial polymers is a lack of selectivity between bacteria and human cells when targeting the cellular membrane,” Michaudel explained. “The key is to strike a right balance between effectively inhibiting bacteria growth and killing several types of cells indiscriminately.”
Michaudel credits the multidisciplinary nature of scientific innovation and the generosity of dedicated researchers across the Texas A&M campus and country as factors in his team’s success in determining the perfect catalyst for their molecule assembly.
“This project was several years in the making and would not have been possible without the help of several groups, in addition to our UMass collaborators,” Michaudel stated in a press release. “For example, to determine the length of our polymers, we had to ship some samples to the Letteri Lab at the University of Virginia, which required the use of an instrument that only a few labs in the country have.” We are particularly appreciative to [biochemistry Ph.D. candidate] Nathan Williams and Dr. Jean-Philippe Pellois at Texas A&M for their assistance in assessing toxicity against red blood cells.”
Michaudel says the team will now focus on improving the activity of its polymers against bacteria — specifically, their selectivity for bacterial cells versus human cells — before moving on to in vivo assays.
“We are in the process of synthesizing a variety of analogs with that exciting goal in mind,” he said.
The team’s paper, which features Michaudel Lab member and Texas A&M chemistry Ph.D. graduate Dr. Sarah Hancock ’23 as first author, can be viewed online along with related figures and captions. Other key contributors from the Michaudel Lab are chemistry graduate student An Tran ’23, postdoctoral scholar Dr. Arunava Maity and former postdoctoral scholar Dr. Nattawut Yuntawattana, who is now an assistant professor of materials science at Kasetsart University in Thailand.
This research was funded primarily by Michaudel’s National Institutes of Health Maximizing Investigators’ Research Award (MIRA) through the National Institute of General Medical Sciences.
