Various in vitro studies and animal studies have provided evidence for a relationship between the proclivity of opportunistic Candida species to adhere to mucosal surfaces (vascular structures such as endothelial cells and subendothelial basement membrane) and their presence in infections. Therefore candidal adherence to human buccal epithelial cells (BECs) is considered as the critical initial step in the pathogenesis of oral candidiasis, which may lead to eventual systemic infection, especially in compromised people. Facing of candidiasis increased, the discovery of new antifungal agents thus remains an important challenge for the scientific community and metal-based drugs might represent an alternative therapeutic route.
The present work reports the results of inhibition of the adhesion of Candida spp. to BECs by two new antifungal agents (ruthenium dithiocarbamate complexes).
The adhesion testing was performed in accordance with method described by literature and it was tested against four Candida species (C. albicans, C. parapsilosis, C. tropicalis and two clinical isolates strains of C. dubliniensis). Fluconazole (FLC) was used as control. The effect of antifungal drugs on candidal adhesion to BECs has been examined following limited exposure (1h) of the isolates to sublethal concentration of the drug. The preparations of BEC were air dried, fixed with heat and stained with gentian violet. The number of adherent yeast cells was quantified by light microscopy at 400 magnification. In each experiment, 50 BECs were observed for adherent yeast cells. Clumped, folded, or overlapping BECs were excluded.
The reference concentration of testing was obtaining by the determination of the Minimum Inhibitory Concentration (MIC). Compared with the fluconazole, one expressive reduction of adhesion to BECs was observed, was higher for Complex 1 against C. parapsilosis (35%) and Complex 2 against C. tropicallis (25%). By relationship ligand/complex there were data similar in all testing (50%). Others results showed adhesion inhibition as good as fluconazole (ligand 1 agaisnt C. albicans and C. dubliniensis CD22; ligand 2 against C. tropicalis and both C. dubliniensis clinical isolates; complex 1 against C. albicans and C. tropicalis; complex 2 against C. dubliniensis CD22).
In conclusion, inhibition of Candida spp. adhesion by ruthenium dithiocarbamate complexes is clearly epithelial cell-specific for preponderance of strains. Therefore, the presence of drug during the "adherence phase" may be of clinical relevance. These results addition others publications (Minimum Inhibitory Concentration from 10–6-10–8 micromol.mL–1 against some important fungal pathogens) proved the possible application of these ruthenium complexes as new drugs for invasive fungal infections .