Nonantibiotic-Based Pseudomonas aeruginosa Biofilm Inhibition with Osmoprotectant Analogues

The current unsustainable usage of antibiotics for clinical and agricultural purposes has resulted in a global spread of antibiotic-resistant bacterial strains. This rapid reduction in antimicrobial potency is directly caused by the strong evolutionary selection pressure of classical antibiotics. One promising strategy to avoid this problem is the development of antivirulence compounds, which seeks to alleviate the aforementioned selection pressure by specifically mitigating pathogenic phenotypes, for example, toxin secretion or biofilm formation, but without killing the bacteria. In this work, we propose a new target for this emerging antivirulence approach and identify through molecular design followed by chemical screening that bacterial osmoprotectant analogues can be used as antivirulence metabolites against biofilm formation. Among the 19 compounds tested, ethylcholine, a biosynthetic precursor of ethyl glycine betaine and previously reported to induce glycine betaine catabolism, was found to most e...