Squalamine and claramine A1 disperse Pseudomonas aeruginosa biofilm

Abstract

Pseudomonas aeruginosa is an opportunistic pathogen that causes both acute and chronic infections, including pneumonia, bloodstream infections, urinary tract infections, and surgical site infections. It poses a significant threat to individuals with chronic lung conditions, particularly those with cystic fibrosis. Squalamine and claramine A1 have emerged as promising antibacterial compounds, exhibiting activity against a broad range of both Gram-positive and Gram-negative bacteria. Beyond their potent antibacterial properties, our findings reveal that sub-inhibitory concentrations of claramine A1 and squalamine can disperse pre-formed P. aeruginosa biofilm without impacting bacterial growth. While claramine A1, but not squalamine, enhances membrane fluidity, the structural difference between these compounds lies primarily in their spermine and spermidine moieties. Notably, we found that spermine, unlike spermidine, was able to both disperse biofilm and increase membrane fluidity. Together, our results suggest that while both compounds are effective at disrupting P. aeruginosa biofilm, they likely act through distinct mechanisms.