Combating bacterial biofilms and related drug resistance: Role of phyto-derived adjuvant and nanomaterials

The emergence of antimicrobial resistance (AMR) in clinical microbes has led to a search for novel antibiotics for combating bacterial infections. The treatment of bacterial infections becomes more challenging with the onset of biofilm formation. AMR is further accelerated by biofilm physiology and differential gene expression in bacteria with an inherent resistance to conventional antibiotics. In the search for innovative strategies to control the spread of AMR in clinical isolates, plant-derived therapeutic metabolites can be repurposed to control biofilm-associated drug resistance. Unlike antibiotics, designed to act on a single cellular process, phytochemicals can simultaneously target multiple cellular components. Furthermore, they can disrupt biofilm formation and inhibit quorum sensing, offering a comprehensive approach to combat bacterial infections. In bacterial biofilms, the first line of AMR is due to biofilms associated with the extracellular matrix, diffusion barriers, quorum sensing, and persister cells. These extracellular barriers can be overcome using phytochemical-based antibiotic adjuvants to increase the efficacy of antibiotic treatment and restrict the spread of AMR. Furthermore, phytochemicals can be used to target bacterial intracellular machinery such as DNA replication, protein synthesis, efflux pumps, and degrading enzymes. In parallel with pristine phytochemicals, phyto-derived nanomaterials have emerged as an effective means of fighting bacterial biofilms. These nanomaterials can be formulated to cross the biofilm barriers and function on cellular targets. This review focuses on the synergistic effects of phytochemicals and phyto-derived nanomaterials in controlling the progression of biofilm-related AMR. IT provides comprehensive insights into recent advancements and the underlying mechanisms of the use of phyto-derived adjuvants and nanomaterials.