Biofilm-associated antibiotic tolerance in the era of multidrug resistance: quorum-sensing mechanisms and emerging therapeutic strategies

Biofilms are highly organised complex structures formed by microorganisms that adhere to surfaces and are embedded with an extracellular polymeric matrix. This matrix provides structural stability, retains nutrients and offers defence against unfavourable environments and antibiotics. Multi-layered molecular mechanisms controlled by quorum-sensing networks are involved in the transition from the planktonic stage to a mature biofilm. Surface attachment, maturation and dispersion are coordinated by these mechanisms, which also provide communication between different species. Biofilm development poses a significant challenge to implants in nosocomial settings and is considered a major threat in the global health care sector and industries, leading to persistent infection. In addition to assessing current biofilm management techniques such as quorum quenching agents, enzymatic matrix disruptions, antimicrobial peptides, nanoparticles and metal complex-based interventions, this review highlights the major regulatory components and molecular mechanisms causing biofilm formation. It also emphasises the necessity to combat biofilm-associated tolerance by highlighting the increasing significance of computational approaches in drug discovery and development of next-generation anti-biofilm therapeutics.