Quorum-quenching enzymes as next-generation antibiofilm therapeutics: mechanisms, applications, and future perspectives.

Quorum sensing (QS) is a form of cell-to-cell communication in bacteria which regulates the activities of biofilm formation, virulence, motility, sporulation and antimicrobial resistance. The growing prevalence of multidrug-resistant pathogens complicates the use of traditional antibiotics. Quorum quenching (QQ) enzymes are considered promising anti-virulence molecules that disrupt bacterial communication without any effect on cell viability. The present review is intended to offer a detailed discussion on QQ enzymes in terms of their modes of action, classification, therapeutic applications and existing challenges towards the treatment of bacterial infections. This includes QS circuits of Gram-positive and Gram-negative bacteria such as LuxI/LuxR, Las/Rhl, Agr and AI-2 systems as well as the structure, catalytic actions and substrates of QQ enzymes like AHL lactonases, acylases, oxidoreductases, paraoxonases and peptide-degrading proteases. In addition to this, some recent developments in biomedical and industrial fields involving QQ enzymes for application in biofilm control, antivirulence treatment, agriculture, aquaculture, water decontamination, coating of medical devices and nanobiotechnology are discussed. Novel drug strategies involving phage-based QQ enzymes, nanostructures, genetically modified bacteria, and the synergy between QQ and antibiotics are explained in detail for the treatment of bacteria-related diseases. In conclusion, QQ enzymes represent a promising and sustainable approach to controls bacterial pathogenicity and biofilm-associated infections.