Theoretical response surface modeling of synergistic antibiofilm activity of gold nanoparticle with amphotericin B on Candida tropicalis biofilms.

CRESPO ANDRADA, KARINA FERNANDA; DA SILVA, MARÍA ANGEL; MALDONADO TORALES, MANUELA; MANRRIQUE HUGHES, IVÁN JEREMÍAS; PARAJE, MARÍA GABRIELA.

Congreso; XVIII Congreso de la Sociedad Argentina de Microbiología General; 2023

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Candida tropicalis is a common member of human and animal microbiota, with invasivecandidiasis having an overall mortality ranging from 55% to 60% in adults, and 26% to 40%in pediatric patients. Consequently, C. tropicalis is included as an emergent pathogen in the“high group” of the World Health Organization Antimicrobial Resistance Division fungalpriority pathogens list. Therapies, such as the use of novel compounds alone or combinedwith a first-line antifungal agent, could be an effective solution for Candida biofilm infections,thereby improving the efficacy and reducing side effects.The present study investigated the synergistic antifungal efficacy of gold nanoparticlesstabilized with cetyltrimethylammonium bromide (CTAB-AuNPs) in combination withAmphotericin B (AmB) on Candida tropicalis biofilms. The Bliss independence model waschosen as a theoretical approach to compare the effects of CTAB-AuNPs in combinationwith AmB. The data interpretation was made by response surface analysis, which served tocalculate a theoretical response surface of an indifferent interaction. All calculations wereperformed using Combenefit software. Besides, experimental results generated with thecheckerboard method, considered to be the reference method, were used to evaluate thesynergistic antifungal effect as a consequence of CTAB-AuNPs/AmB interaction. Theminimal biofilm inhibitory concentration (MBIC) was determined and were used (MBIC/6,MBIC/4, MBIC/2, MBIC, MBIC*2, MBiC*4). The fractional inhibitory concentration (FIC) isa widely accepted means of measuring interactions by calculating the fractional inhibitoryconcentration index (FICi) using the following equations: FICi = (MBIC in combination/MBICAuNPs alone) + (MBIC in combination/MBIC AmB alone). The interaction is scored as:≤ 0.5 = synergistic; > 0.5 to ≤1.0 are additive; >1.0 and ≤4.0 = indifferent; > 4.0 =antagonistic.Synergy was detected using a checkerboard with the data being interpreted by twodifferent approaches, FICi or response surface analysis. Combinations of AuNPs plus AmBresulted in at least a 4-fold decrease in the MBIC values of mature C. tropicalis biofilm,thereby demonstrating synergy (FICi = 0.5). The combination of AuNPs with AmB increasesantifungal activity, as it can improve their efficacy by combining different mechanisms ofaction. This combination is a promising strategy for improving efficacy, reducing dosages,shortening the duration of antifungal therapy, and consequently, reducing side effects. Inaddition, relapse may be prevented by the action of this combination on sessile cells directlyassociated with recurrent or chronic infections