Antimicrobial effects and mechanism of action of carboxymethyl chitosan-loaded silver ion complexes against drug-resistant Aspergillus fumigatus

Based on the escalating challenge of drug-resistant Aspergillus fumigatus infections, this study developed a silver ion-loaded carboxymethyl chitosan (CMCh-Ag⁺) nanocomposite as a potent antifungal agent. The composite was successfully synthesized and characterized, revealing distinct physicochemical properties, uniform dispersion, and confirmed coordination between CMCh and Ag⁺. In vitro evaluations, including minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC), growth curve, and plate spotting assays, demonstrated that CMCh-Ag⁺ exhibited significantly superior antifungal efficacy against multiple A. fumigatus strains (including azole-resistant isolates) compared to CMCh or Ag⁺ alone. In vivo experiments using a Galleria mellonella infection model confirmed the enhanced therapeutic effect and biocompatibility of CMCh-Ag⁺. Investigations into the mechanism-related phenotypes revealed that CMCh-Ag⁺ significantly removed fungal biofilm and was associated with a substantial accumulation of intracellular reactive oxygen species (ROS), correlating with fungal cell death. This research highlights the preliminary potential of CMCh Ag⁺ as a candidate strategy to combat drug-resistant A. fumigatus infections, warranting further investigation in mammalian models to assess its clinical translational prospects.