Abstract
Candida spp. are one of the most common fungal pathogens. Biofilms formed by Candida albicans offer resistance mechanisms against most antifungal agents. Therefore, development of new molecules effective against these microorganisms, alone or in combination with antifungal drugs, is extremely necessary. In the present work, we carried out a screening process of different cationic carbosilane dendritic molecules against C. albicans. In vitro activity against biofilm formation and biofilms was tested in both Colección Española de Cultivos Tipo (CECT) 1002 and clinical C. albicans strains. Cytotoxicity was studied in human cell lines, and biofilm alterations were observed by scanning electron microscopy (SEM). Antifungal activity of the carbosilane dendritic molecules was assessed by monitoring cell viability using both established and novel cell viability assays. One out of 14 dendritic molecules tested, named BDSQ024, showed the highest activity with a minimum biofilm inhibitory concentration (MBIC) for biofilm formation and a minimum biofilm damaging concentration (MBDC) for existing biofilm of 16–32 and 16 mg/L, respectively. Synergy with amphotericin (AmB) and caspofungin (CSF) at non-cytotoxic concentrations was found. Therefore, dendritic compounds are exciting new antifungals effective at preventing Candida biofilm formation and represent a potential novel therapeutic agent for treatment of C. albicans infection in combination with existing clinical antifungals.
Highlights
Candida is a fungal opportunistic pathogen responsible for serious infections in humans, including candidiasis, especially in immunocompromised individuals [1,2]
The compound BDSQ024 was tested against a clinical C. albicans strain and observed lower minimum biofilm inhibitory concentration (MBIC) and minimum fungicidal concentration (MFC) values (MBIC and MFC: 8 mg/L) than C. albicans Colección Española de Cultivos Tipo (CECT) 1002 (MBIC: 16–32 mg/L and MFC: 32 mg/L). These results show that BDSQ024 has activity against C. albicans and prevents biofilm formation at concentrations between 8–32 mg/L
The data obtained in this study showed that BDSQ024 had a fungistatic effect against biofilm and severely damaged C. albicans cells as clearly observed using scanning electron microscopy (SEM)
Summary
Candida is a fungal opportunistic pathogen responsible for serious infections in humans, including candidiasis, especially in immunocompromised individuals [1,2]. Biofilm formation has clinical implications and continues to be a major problem, contributing to increased mortality rates associated to these fungal infections Medical devices, such as catheters or prostheses [6,7], are common niches where biofilms manage to adhere and develop, and once formed, these biofilms provide resistance to high concentrations of antifungal compounds. The extracellular matrix is composed of self-produced polysaccharides [6,7,11], which offer protection to cells that comprise the biofilm against the host’s immune system This matrix blocks drugs from penetrating the biofilm and prevents antifungal compounds from reaching their target. This often results in the development of drug resistance that causes severe health problems, including bloodstream infections, in hospitalized patients [8,12]. Biofilms are an important reservoir of infections and represent a key target for the development of novel antifungal therapeutics
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