Endophyte-Mediated Green Synthesis of Metallic Nanoparticles: Mechanistic Insights, Antibiofilm Efficacy, and Translational Challenges

Antimicrobial resistance, a major health problem for the world’s population, is caused by pathogenic bacteria capable of forming biofilms, claiming 4.95 million lives each year, according to WHO (World Health Organization) data, and could escalate up to 10 million annual deaths by 2050 if unchecked. Biofilms are the structured microbial populations surrounded and composed by an EPS (Extracellular Polymeric Substance) matrix to protect themselves from host immune responses and antibiotics, which makes the infections persistent and difficult to treat. Current global approaches to the pathogenic microbes to address AMR (Antimicrobial Resistance) are solved by different alternative strategies; one such strategy is nanotechnology, a rapidly developing field in the twenty-first century, using metallic nanoparticles that are generally characterized by dimensions within the range of 1–100 nm, have distinct structural and functional properties from bulk materials, and perform higher penetration in the cell membranes of pathogenic microbes. Overall, the present review offers a detailed overview of significant knowledge gaps regarding scalability, long-term safety, and the mechanistic pathway of nanoparticles synthesized from endophytic microorganisms. The inclusion also summarizes a comparison of bacterial and fungal endophyte-mediated metallic nanoparticles with plant-mediated metallic nanoparticles, particularly in terms of metabolite diversity, synthesis efficiency, size, nanoparticle stability, toxicity, antimicrobial activity, and antibiofilm potential. The novelty lies in how the efficacy of endophytic-mediated metallic nanoparticles acts against the defense mechanisms of pathogenic microorganisms in terms of molecular pathways and processes associated with ROS (Reactive Oxygen Species), disruption of membrane integrity, quorum sensing interference, EPS (Extracellular Polymeric Substance) degradation, DNA and protein disruption, and biofilm collapse. However, nanoparticles synthesized from endophytic microorganisms face translational challenges and limitations that need to be addressed.