Unlocking monosaccharide composition of capsular polysaccharide and lipopolysaccharide to combat Pseudomonas...

The pathogen Pseudomonas aeruginosa produces capsular polysaccharide (CPS) and lipopolysaccharide (LPS) as key pathogenic factors. However, the responses of their monosaccharide compositions to antibacterial agents remain poorly understood. This study characterized and compared the monosaccharide composition and proportion in CPS and LPS of P. aeruginosa strains ATCC 9027 and ATCC 15442 after treatment with a polysaccharide modulator, quinazolin-6-yl isoindolinone (IQE-X1). Monosaccharide levels were analyzed using optimized ion-exchange chromatography. The antibacterial activity, biofilm suppression, and cellulase inhibition of IQE-X1 were also assessed. Results showed that CPS and LPS from both strains contained eight monosaccharides: rhamnose, arabinose, glucosamine, galactose, glucose, xylose, mannose, and ribose, with strain-specific abundance profiles. ATCC 9027 was rich in ribose, while ATCC 15442 had high glucose and ribose in CPS, and high ribose and glucosamine in LPS. Neither strain contained trehalose, galacturonic acid, or glucuronic acid. IQE-X1 exhibited antibacterial activity, with IC₅₀ values of 0.39-4.12 μg/mL for ATCC 9027 and 0.36-7.97 μg/mL for ATCC 15442 after 16 h of treatment. It also inhibited 99.5 % of biofilm formation and 82.4 % of cellulase activity in ATCC 9027. IQE-X1 reduced all monosaccharide levels in the CPS of both strains, with distinct reduction patterns for each strain. Furthermore, it altered LPS composition: ATCC 9027 showed increased glucosamine and mannose levels, while ATCC 15442 exhibited a significant decrease in arabinose, galactose, and glucose. These findings reveal strain-specific monosaccharide profiles in CPS and LPS and highlight a potential strategy to combat P. aeruginosa by modulating monosaccharide composition and proportion.