Combating biofilm formation and bacterial killing: N-acetylcysteine's efficacy against Pseudomonas aeruginosa in urinary catheters

Uropathogenic Pseudomonas aeruginosa is a significant contributor to catheter-associated urinary tract infections (CA-UTIs), distinguished by its unique biofilm-forming properties compared to other strains. Despite its clinical significance, optimized strategies for biofilm eradication in the bladder and on catheters remain limited. Thus, the aim of this study was to highlight the potent antibacterial and biofilm-inhibitory effects of N-acetyl cysteine (NAC) against uropathogenic P. aeruginosa. Additionally, we sought to investigate its effect against catheter obstruction caused by P. aeruginosa in a patient, and whether this phenomenon can be replicated in vitro to underscore the urgency of addressing this critical challenge. We demonstrated that uropathogenic P. aeruginosa form thick, mucoid biofilms in vitro that can heavily occlude catheters, with bacterial titres of between 10⁸ and 10¹¹ CFU/cm, thus impairing catheter functionality. Furthermore, treatment with NAC significantly reduced viable bacteria by > 4_log10 (p < 0.01), and inhibited biofilm formation and associated obstruction till experiment endpoint (96h). NAC also displayed significant bactericidal activity (p < 0.001) against P. aeruginosa and significantly impeded bacterial attachment and aggregation through modulation of colloidal forces and change in the structure of the bacterial cell surface, thus impairing the bacterium's ability to initiate biofilm development. Mechanistically, NAC alters the bacterial surface structure, disrupting biofilm-associated virulence. Hence our study found that NAC treatment physically disrupts uropathogenic P. aeruginosa biofilms and significantly alters its virulence. Our novel findings highlight the dual bactericidal and anti-biofilm properties of NAC in vitro, offering valuable insights into its potential application for preventing P. aeruginosa biofilm formation and catheter blockage in CA-UTI management.