(565a) New Insights into the Mechanism of Action of Cationic ?-Conjugated Polyelectrolytes Against Bacteria

The emergence of antibiotic-resistant bacteria has become one of the biggest health concerns in the world due to the misuse and overuse of antibiotics. When bacteria become resistant to antibiotics, they can stop the activity of the antibiotics. As a result, many traditional antibiotics are not effective anymore. It has been shown that cationic π-conjugated oligo- and polyelectrolytes can interact with bacteria through electrostatic and hydrophobic interactions, and kill or inhibit the growth of the antibiotic-resistant bacteria. In this work, we have designed a phenylene-based cationic, π-conjugated polyelectrolyte (CCPE) and studied its antibacterial activity against a series of wild-type and antibiotic-resistant bacteria. Our results showed that just a 3-min treatment with CCPE can lead to almost complete growth inhibition of both wild-type and ampicillin-resistant E. coli. We took a holistic approach to understand the binding and antimicrobial action mechanism of CCPE against ampicillin-resistant E. coli. Zeta potential measurement of treated cells confirmed that CCPE binds to bacterial outer membrane electrostatically, and causes the surface charge reversal of bacteria. We explored the morphological changes of the bacterial outer membrane using atomic force microscopy (AFM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM)). The images showed clear signs of alterations (blebbing, release of components, increase in surface roughness) of the bacterial outer cell envelope. The elastic modulus mapping across the cells, done using AFM nanoindentation, showed that the stiffness of the bacteria decreased upon CCPE treatment. The lipid loss (from lipidomics) and extracellular formation (from electron microscopy), together with the information obtained from metabolomics studies, nicely explains the underlying mechanism of growth inhibition of antibiotic-resistant bacteria caused by CCPE.