Near-infrared activated Fosfomycin-Silver nanoparticles against multidrug-resistant bacteria: Microbiological and molecular insights into resistance modulation.

Globally, public health is seriously threatened by multidrug-resistant (MDR) microorganisms. This work investigates the potential benefit of using Fosfomycin (FOS, 71 μg/mL)-loaded near-infrared (NIR, 808 nm, 1 W/cm2 for 10 min, penetration depth ≈ 8-10 mm) responsive plasmonic silver nanoparticles (AgNPs, 100 μg/mL) as a new antibacterial approach against MDR Escherichia coli (E. coli) and methicillin-resistant Staphylococcus aureus (MRSA). Synthesized AgNPs were loaded with FOS and then analyzed by UV-Vis spectrophotometry, dynamic light scattering, zeta potential, transmission electron microscopy, FTIR spectroscopy, XRD, and thermogravimetric analysis. Using an 808 nm NIR laser, the photothermal effect of NIR-responsive AgNPs was evaluated, and UV-Vis spectrophotometry was used to measure FOS release. We determined the antimicrobial effectiveness against MDR E. coli and MRSA using growth curves, CFU, disc diffusion, MIC, MBC, and live/dead assays. Using NIH/3T3 cells, cytotoxicity was measured. Evaluation of ROS production, oxidative stress indicators, efflux pumps, and β-lactamase gene expression was done. We discovered extremely favorable bacteria growth inhibition and photothermally stimulated antibacterial action with minimal cytotoxicity, providing a platform for improved antimicrobial therapy.