Improved photodynamic inactivation of resistant Nakaseomyces glabrata yeasts and biofilms mediated by ZnTE-2-PyP4+ porphyrin combined with silver nanoparticles

Abstract

Nakaseomyces glabrata is a high-priority fungal pathogen due to its incidence and antifungal resistance. Photodynamic inactivation (PDI) can offer a promising approach against resistant N. glabrata, particularly when the advantageous photophysical properties of Zn(II) porphyrins can be enhanced by the plasmonic effect of metal nanoparticles (NPs). Herein, the association of ZnTE-2-PyP4+ porphyrin (ZnP-ethyl) with AgNPs (stabilized with polyvinylpyrrolidone, PVP) in PDI against yeasts and biofilms of resistant N. glabrata strains was investigated. AgNPs/ZnP-ethyl (NE) systems were prepared, and physicochemical characterizations indicated the interaction and spectral overlap between AgNPs and ZnP-ethyl, prerequisites for harnessing the plasmonic effect. Moreover, AgNPs had a minimal effect on ZnP-ethyl fluorescence lifetime. To investigate the role of AgNPs and strain susceptibility in PDI, yeast interactions with NE and ZnP-ethyl were assessed by fluorescence microscopy, which indicated that, in general, AgNPs facilitated the internalization of ZnP-ethyl by cells. Interestingly, HGV14 yeasts, which were unable to form biofilm, exhibited the lowest susceptibility to NE-PDI, likely due to reduced cell interaction relative to the other strains. PDI using ZnP-ethyl alone at 1.5 μM reduced HGV11 and HGV20 yeasts by 1 log10, whereas NE-mediated PDI eradicated cells using 4–5-fold lower ZnP-ethyl concentrations. In biofilms, NE-PDI reduced the viability by ∼75% and induced high cell death to a much greater extent compared to other irradiated groups. Therefore, NE boosted the PDI of yeasts and biofilms across all resistant N. glabrata strains, likely driven by plasmonic effect and enhanced cell interaction promoted by PVP-AgNPs, making NE-PDI a promising strategy for combating resistant microorganisms.