New synthetic polymers kill superbugs without inducing antibiotic resistance and without being harmful

Good news! Defeating harmful bacteria once and for all is only a matter of time! The publication of this research is dating back to December 2023, but it is very relevant.

"... antibiotic polymers are a decent step in that direction. These synthetic molecules latch onto and disrupt the outer membranes of bacteria, in a form of attack that the bugs can’t develop resistance to. ...
The key is a catalyst called AquaMet, which can handle a high concentration of charges and is water-soluble. That charge tolerance is important – antibacterial polymers work because their positive charge attracts them to the negative charge of the bacteria. ...

In lab tests, the new polymers were found to be active against the two main groups of bacteria – gram-positive, such as Methicillin-resistant Staphylococcus aureus (MRSA), and gram-negative, such as E. coli. This suggests the molecules will work against a variety of superbugs. Importantly, the drugs also worked at low concentrations. ..."

From the significance and abstract:

"Significance

... Cationic polymers are a promising class of bioactive agents, which trigger bacterial cell death through physical disruption of their membranes. However, polymerization processes must be designed to optimize the therapeutic potential of cationic polymers. In this work, we report the precise synthesis of main-chain cationic polymers via controlled ring-opening metathesis polymerization of N-methylpyridinium-fused norbornenes. These charged polymers were found to be active against both Gram-positive and -negative bacteria. Additionally, modification of the chain length and pyridinium core allowed for the improvement of their selectivity for bacterial cells over human red blood cells.

Abstract

Cationic polymers have been identified as a promising type of antibacterial molecules, whose bioactivity can be tuned through structural modulation. Recent studies suggest that the placement of the cationic groups close to the core of the polymeric architecture rather than on appended side chains might improve both their bioactivity and selectivity for bacterial cells over mammalian cells. However, antibacterial main-chain cationic polymers are typically synthesized via polycondensations, which do not afford precise and uniform molecular design. Therefore, accessing main-chain cationic polymers with high degrees of molecular tunability hinges upon the development of controlled polymerizations tolerating cationic motifs (or cation progenitors) near the propagating species. Herein, we report the synthesis and ring-opening metathesis polymerization (ROMP) of N-methylpyridinium-fused norbornene monomers. The identification of reaction conditions leading to a well-controlled ROMP enabled structural diversification of the main-chain cationic polymers and a study of their bioactivity. This family of polyelectrolytes was found to be active against both Gram-negative (Escherichia coli) and Gram-positive (Methicillin-resistant Staphylococcus aureus) bacteria with minimal inhibitory concentrations as low as 25 µg/mL. Additionally, the molar mass of the polymers was found to impact their hemolytic activity with cationic polymers of smaller degrees of polymerization showing increased selectivity for bacteria over human red blood cells."

New antibiotic family kills superbugs in a way they can't resist

Texas A&M Team Develops Polymers That Can Kill Bacteria Dr. Quentin Michaudel and his research team have created a new family of polymers capable of killing bacteria without inducing antibiotic resistance — a major step in the fight against superbugs like E. coli and MRSA.

Ring-opening metathesis polymerization of N-methylpyridinium-fused norbornenes to access antibacterial main-chain cationic polymers (no public access)