Targeting Response Regulator PprB Protein With Natural Compounds to Develop Novel Therapies Against Pseudomonas aeruginosa

The pathogen Pseudomonas aeruginosa (P. aeruginosa) is recognized as an international pathogen of significance due to its multidrug resistance and strong ability to create biofilm as the basis of chronic and device-associated infections. The two-component regulatory system PprAB is important in the biofilm network, where the response regulator PprB regulates binding, aggregation, and biofilm production in the extracellular environment. The current research took PprB as a probable anti-biofilm target and assessed two biogenic ligands, atropine and α-ketoglutarate, as potential inhibitory substrates. PprB was purified and structural studies were conducted to investigate ligand-binding interactions and structural stability. Conserved regulatory motifs were identified through sequence analysis and multiple sequence alignments. Biofilm inhibition, combinatory assays, antimicrobial study, fluorescence spectroscopy, and FESEM were conducted to experimentally validate the interactions and functional analysis of PprB. Collectively, our findings highlight PprB as a promising therapeutic target and demonstrate the potential of atropine and α-ketoglutarate as effective modulators of P. aeruginosa biofilm formation.