Comparison of Antifungal Efficacy of Biosynthesized versus Chemically Synthesized Silver Nanoparticles against Candida Species: Phytochemical Surface Chemistry at the Nano-Fungal Biointerface

We report a one-step biosynthesis of silver nanoparticles (Fa-AgNPs) using an aqueous Fagonia indica extract and benchmark their activity at the nano-fungal biointerface against Candida albicans and the emerging, multidrug-resistant pathogen Candida auris. Fa-AgNPs were polydisperse and quasi-spherical, with a smaller mean diameter than citrate-capped chemically synthesized AgNPs (Cs-AgNPs) (19.41 ± 7.32 nm vs. 29.01 ± 2.63 nm). Fa-AgNPs outperformed Cs-AgNPs on both species, with MICs of 31.25 vs 125 µg/mL against C. albicans and 3.91 vs 7.81 µg/mL against azole-resistant C. auris. Against C. auris, Fa-AgNPs were at least 64-fold more potent than fluconazole (3.91 vs >250 µg/mL). To our knowledge, this is the first report of F. indica-mediated AgNPs achieving an MIC below 4 µg/mL against this pathogen. Mechanistically, Fa-AgNPs delayed the onset of growth, elevated intracellular ROS in C. albicans, and induced catalase-based antioxidant defense in both species; SEM showed loss of budding cells and extracellular polymeric substances, together with a transition from smooth to rough surfaces and cell-wall damage, in both species, consistent with a primarily oxidative interfacial mechanism. Hemolysis assays indicated acceptable blood compatibility at the lowest concentration tested (2.5 µg/mL), with hemolysis increasing at higher concentrations.