Antibiotic-resistant bacteria have become a rapidly growing threat to public health. Each year, they account for more than 2.8 million infections, according to the US Centers for Disease Control and Prevention. Without new antibiotics, even common injuries and infections have the potential to become fatal.
Scientists are now one step closer to eliminating this threat, thanks to a Texas A&M University collaboration that developed a new family of polymers capable of killing bacteria without causing antibiotic resistance by disrupting the membrane of these microorganisms.
“The new polymers we synthesized could help fight antibiotic resistance in the future by providing antibacterial molecules that work through a mechanism to which bacteria do not seem to develop resistance,” said Dr. Quentin Michaudel, assistant professor in the Department of Chemistry and lead researcher on the study, published Dec. 11 at Proceedings of the National Academy of Sciences (PNAS).
Working at the interface of organic chemistry and polymer science, the Michaudel lab was able to synthesize the new polymer by carefully designing a positively charged molecule that can be stitched together many times to form a large molecule from the same repeating charged pattern using a carefully selected catalyst called AquaMet. According to Michaudel, this catalyst proves to be key since it must tolerate a high charge concentration and also be water-soluble — a feature he describes as unusual for this type of process.
After achieving success, the Michaudel Lab tested its polymers against two major types of antibiotic-resistant bacteria — E. coli and Staphylococcus aureus (MRSA) — in collaboration with Dr. Jessica Schiffman at the University of Massachusetts Amherst. Pending these results, the researchers also tested the toxicity of their polymers against human red blood cells.
“A common problem with antibacterial polymers is the lack of selectivity between bacteria and human cells when targeting the cell membrane,” explained Michaudel. “The key is to strike the right balance between effectively inhibiting bacterial growth and killing several cell types indiscriminately.”
Michaudel credits the interdisciplinary nature of scientific innovation and the generosity of dedicated researchers on Texas A&M’s campus and country as factors in his team’s success in identifying the perfect catalyst to assemble their molecules.
“This project has been several years in the making and would not have been possible without the help of many groups, beyond our partners at UMass,” Michaudel said. “For example, we had to send some samples to the Letter Lab at the University of Virginia to determine the length of our polymers, which required the use of an instrument that few labs in the country have. We are also extremely grateful for [biochemistry Ph.D. candidate] Nathan Williams and Dr. Jean-Philippe Pellois here at Texas A&M, who provided their expertise in evaluating red blood cell toxicity.”
Michaudel says the team will now focus on improving their polymers’ activity against bacteria — specifically, their selectivity for bacterial cells versus human cells — before moving on to in vivo analyses.
“We are in the process of synthesizing a variety of analogs with this exciting goal in mind,” he said.
The team’s work, which includes Michaudel Lab member and Texas A&M chemistry Ph.D. The 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 fellow Dr. Arunava Maity and former postdoctoral fellow Dr. Nattawut Yuntawattana, who is now an assistant professor of materials science at Kasetsart University in Thailand.
This research was primarily funded by the Michaudel National Health Maximization Research Award (MIRA) through the National Institute of General Medical Sciences.
A native of La Rochelle, France, Michaudel joined the Texas A&M Chemistry faculty in 2018 and holds a joint appointment in the Department of Materials Science and Engineering. In addition to the 2020 NIH MIRA, his career honors to date include a 2022 National Science Foundation Faculty Early Career Development Award, a 2022 American Chemical Society Young Investigator Award for Polymer Materials: Science and Engineering (PMSE), and a 2021 Thieme Award Chemistry Journals.