Biosynthesized Silver Selenide Nanoparticles from Meyerozyma guilliermondii as a Novel Adjuvant to Revolutionize Gentamicin Therapy

The increasing prevalence of antibiotic resistance necessitates the development of novel antimicrobial agents and therapeutic strategies. This study reports the extracellular biosynthesis of silver selenide nanoparticles (Ag₂Se NPs) using <i>Meyerozyma guilliermondii</i> PG-1 and evaluates their antimicrobial and antibiofilm efficacy, both alone and in combination with gentamicin. The NPs were thoroughly characterized, confirming their nanoscale size, crystallinity, and biomolecule-mediated stability. Ag₂Se NPs exhibited broad-spectrum antibacterial activity against Gram-positive (<i>Staphylococcus aureus</i>) and Gram-negative (<i>Pseudomonas aeruginosa</i>, <i>Escherichia coli</i>) pathogens and showed strong synergy with gentamicin, particularly against <i>P. aeruginosa</i> and <i>E. coli</i>, as demonstrated through checkerboard and time-kill assays. The NPs also significantly inhibited biofilm formation and disrupted pre-formed biofilms. Mechanistic studies revealed that the antibacterial effects involved membrane disruption, ATP leakage, and elevated oxidative stress, while gene expression analysis in <i>S. aureus</i> indicated triggered stress responses related to biofilm formation. These findings suggest that biosynthesized Ag₂Se NPs represent a promising synergistic agent for enhancing antibiotic efficacy and combating biofilm-related infections.