Candida tropicalis is a common member of human and animal microbiota, with invasive candidiasis having an overall mortality ranging from 55% to 60% in adults, and 26% to 40% in pediatric patients and is included as an emergent pathogen in the “high group” of the World Health Organization Antimicrobial Resistance Division fungal priority pathogens list.
We studied the antifungal activity of gold nanoparticles (AuNPs) stabilized with cetyltrimethylammonium bromide (CTAB-AuNPs) and those conjugated with cysteine, in combination with Amphotericin B (AmB), on sessile and persister cells (PCs) of Candida tropicalis biofilms.
The PC model was used and synergistic activity was tested by the checkerboard assay. Biofilms were studied by crystal violet and scanning electron microscopy. The fractional inhibitory concentration (FIC) is a widely accepted means of measuring interactions by calculating the fractional inhibitory concentration index (FICi) using the following equations: FICi = (MBIC in combination/MBIC AuNPs alone) + (MBIC in combination/MBIC AmB alone). The Bliss independence model was chosen as a theoretical approach to compare the effects of AuNPs in combination with AmB. The data interpretation was made by response surface analysis, which served to calculate a theoretical response surface of an indifferent interaction.
Mature biofilms decreased in biomass after the combination of both AuNPs and AmB. A biofilm reduction of 97.29% was obtained with CTAB-AuNPs plus AmB, corresponding to 0.05 FICi points (synergism). Meanwhile, by conjugating cys-AuNPs with AmB, a 91.66% biofilm reduction was obtained, resulting in a FICi value of 0.75 (additive). Analysis of the checkerboard data by the response surface approach led to similar results. For the combination of CTAB-AuNPs with AmB, the SUM-SYN-ANT metric ranged from 5.69 to 36.06, with a mean of 30.91.
Our improved understanding of how these AuNPs aid in the fight against biofilm-associated candidiasis and the development of new approaches to eradicate PC biofilms have great clinical relevance in the treatment of mycoses, which has seen an increasing number of at-risk patients.
