Antivirulent Properties of the Adamantane Derivative 4-(Adamanthyl-1)-1-(1-Aminobutyl) Benzene Against Pseudomonas Aeruginosa

Abstract

Background. Pseudomonas aeruginosa is an opportunistic pathogen characterized by a high level of virulence and classified as a microorganism with a critical priority for the development of new antimicrobial drugs. Targeting virulence factors is one of the promising approaches in antimicrobial drug development. Objective. Investigating the antivirulence properties of the aminoadamantane derivative 4-(adamantyl-1)-1-(1-aminobutyl)benzene against P. aeruginosa. Methods. The minimum inhibitory concentration (MIC) of 4-(adamantyl-1)-1-(1-aminobutyl)benzene (code AM-166) against the clinical strain P. aeruginosa 449 was determined using the serial microdilution method. We conducted quantitative real-time PCR to assess the impact of AM-166 on gene expression. Additionally, we investigated the synthesis of pyocyanin, hemolytic and protease activity, as well as motility of P. aeruginosa under the influence of AM-166. Results. The obtained data indicate that the MIC of the AM-166 compound is 100 μg/ml. When exposed to AM-166 (at 0.5 MIC), we observed a decrease in the transcriptional activity of the lasI, lasR, pqsR, aprA, exoA, and exoS genes, along with an increase in the expression of the rhlR gene. Notably, AM-166 did not alter the expression of the toxA gene. Furthermore, AM-166 increased the production of pyocyanin, had no significant effect on protease activity, and inhibited both hemolytic activity and motility in P. aeruginosa 449. Conclusions. The adamantane derivative AM-166 disrupts the functioning of the Quorum sensing systems and pathogenicity of P. aeruginosa while also altering the expression of genes that regulate the synthesis of virulence factors.