Deciphering the Dilemma of Community Behavior Promotion and Inhibition by Cationic Bactericide-coated Nanoparticles in Gram-Negative Bacteria

Cationic bactericidal-coated gold nanoparticles are known to effectively prevent Gram-negative bacterial initial adhesion and community behavior development by strongly binding to bacterial surfaces and disrupting the cell membranes. However, such nanoparticles have been recently shown to unintentionally promote community behavior in Gram-negative bacteria because of the bacterial stress response. To find whether these contradictory findings are due to emerging stress response or poorly understood nanoparticle interactions of Gram-negative bacteria, in this work, we treated high population curli-producing Gram-negative <i>Escherichia coli</i> with cationic antibiotic/antiseptic-coated gold nanoparticles and followed the consequences in details using a variety of physical methods and controls. Parallelly, we employed standard biological assays commonly used to detect community behavior in bacteria. Biological assays yielded contradictory results some inferring promotion while others inferring inhibition. However, physical methods revealed that promotion and inhibition observations resulted from physical interactions without any bacterial response being involved. Using physical methods, we further demonstrated that macromolecules of cationic antibiotics and antiseptics exhibit similar consequences as nanoparticles, independent of inhibitory concentration. Overall, the results emphasize the need to consider physical interactions, rather than relying solely on standard biological assays, when evaluating the inhibition or promotion of community behavior by cationic antibiotic/antiseptic-coated nanoparticles or free cationic antibiotics/antiseptics against Gram-negative bacteria.