Pseudomonas aeruginosa is an opportunistic pathogen causing acute and chronic infections, especially in immunocompromised patients. Its remarkable adaptability and resistance to various antimicrobial treatments make it difficult to eradicate. Its persistence is enabled by its ability to form a biofilm. Biofilm is a community of sessile micro-organisms in a self-produced extracellular matrix, which forms a scaffold facilitating cohesion, cell attachment, and micro- and macro-colony formation. This lifestyle provides protection against environmental stresses, the immune system, and antimicrobial treatments, and confers the capacity for colonization and long-term persistence, often characterizing chronic infections. In this review, we retrace the events of the life cycle of P. aeruginosa biofilm, from surface perception/contact to cell spreading. We focus on the importance of extracellular appendages, mechanical constraints, and the kinetics of matrix component production in each step of the biofilm life cycle.

Background/Objectives: Biofilm-associated infections pose a major clinical challenge since bacteria within biofilms exhibit highly antibiotic tolerance. Pseudomonas aeruginosa forms persistent biofilms that cause chronic infections in vulnerable patients, including those with cystic fibrosis, burns, or medical implants. Such biofilm-associated chronic infections require prolonged treatments that promote antimicrobial resistance. To address this, recent strategies focus on enhancing biofilm dispersion. Methods: Thirty-six N-arylimino-1,2,3-dithiazoles were screened for their biofilm dispersal activity using a crystal violet assay. Their cytotoxicity was assessed on A549 and HaCat eukaryotic cells. Moreover, their influence on bacterial growth and virulence was investigated. Lastly, fluorescence anisotropy was used to measure membrane fluidity to obtain the first insights on the mechanism of action of these chemicals. Results: Our results showed that quinazoline-derivatives of imino-1,2,3-dithiazoles display biofilm dispersion activity. These compounds do not increase virulence through pyocyanin production, do not modify the growth kinetics of P. aeruginosa, and do not show cytotoxicity towards eucaryotic cells. Conclusions: These findings highlight the potential use of N-arylimino-1,2,3-dithiazole-derived compounds as safe and effective dispersal agents of P. aeruginosa biofilms.