Synergistic Antifungal Interaction between Pseudomonas aeruginosa LV Strain Metabolites and Biogenic Silver Nanoparticles against Candida auris
Laís Fernanda de Almeida Spoladori, Gabriella Maria Andriani, Isabela Madeira de Castro, Helena Tiemi Suzukawa, Ana Carolina Ramos Gimenes, Guilherme Bartolomeu-Gonçalves, Kelly Ishida, Gerson Nakazato, Phileno Pinge‐Filho, Rayanne Regina Beltrame Machado, Celso Vataru Nakamura, Galdino Andrade, Eliandro Reis Tavares, Lucy Megumi Yamauchi, Sueli Fumie Yamada‐Ogatta
Abstract
Candida auris has been found to be a persistent colonizer of human skin and a successful pathogen capable of causing potentially fatal infection, especially in immunocompromised individuals. This fungal species is usually resistant to most antifungal agents and has the ability to form biofilms on different surfaces, representing a significant therapeutic challenge. Herein, the effect of metabolites of Pseudomonas aeruginosa LV strain, alone and combined with biologically synthesized silver nanoparticles (bioAgNP), was evaluated in planktonic and sessile (biofilm) cells of C. auris. First, the minimal inhibitory and fungicidal concentration values of 3.12 and 6.25 μg/mL, respectively, were determined for F4a, a semi-purified bacterial fraction. Fluopsin C and indolin-3-one seem to be the active components of F4a. Like the semi-purified fraction, they showed a time- and dose-dependent fungicidal activity. F4a and bioAgNP caused severe changes in the morphology and ultrastructure of fungal cells. F4a and indolin-3-one combined with bioAgNP exhibited synergistic fungicidal activity against planktonic cells. F4a, alone or combined with bioAgNP, also caused a significant decrease in the number of viable cells within the biofilms. No cytotoxicity to mammalian cells was detected for bacterial metabolites combined with bioAgNP at synergistic concentrations that presented antifungal activity. These results indicate the potential of F4a combined with bioAgNP as a new strategy for controlling C. auris infections.