In vitro effects of quorum sensing molecules (Tryptophol) on the growth of antifungal drug-resistant fungi
Keywords:fungal quorum sensing molecules, tryptophan, fibroblast cells, cytotoxicity cells
Human pathogenic fungi such as Candida spp. and Aspergillus spp. have been shown to increase the frequency of antifungal resistance, especially in the Azole group. The previous study found that tryptophol, which is classified as fungal quorum sensing molecules (QSMs), plays a role in fungal growth inhibition. Therefore, in the present study aimed to investigate the potential of tryptophol to control the growth of both drug susceptibility and Azole resistant strains of C. albicans and A. fumigatus in vitro, as well as to evaluate the inhibitory concentration of tryptophol on the cytotoxicity of fibroblast cells. This study results showed that tryptophol at the Minimum Inhibitory Concentration (MIC) of 2 mM and 8 mM was able to inhibit the growth of C.albicans and A. fumigatus, respectively. In addition, tryptophol at concentrations of 2 mM and 4 mM did not cause damage to mitochondria and cytotoxicity after treatment with fibroblast cells by MTT Assay. The percentage of cell viability was 113.86±9.34% and 105.08±13.66%, respectively. However, tryptophol at a concentration of 8 mM can produce a cytotoxic effect. When examining the apoptosis of fibroblast cells using Ethidium Bromide-Acridine Orange Staining Assay, we found that tryptophol at concentrations of 2 mM and 4 mM was able to induce fibroblast apoptosis by 46% and 40.2%, respectively. Tryptophol at concentrations of 8 to 64 mM and was able to induce 100% of fibroblast cell apoptosis. Moreover, tryptophol at concentrations of 2 mM and 4 mM was able to down-regulate the expression of Caspase-8 andCARD-9 genes and to up-regulate the Caspase-8 andCARD-9 genes when treated at concentrations of 8 to 64 mM. From the results, this study showed that the tryptophol at a concentration of 8mM was capable of inhibiting growth both drug susceptibility and Azole resistant strains of C. albicans and A. fumigatus. However, the utilization of tryptophol is limited to fibroblast cells in the induction of cell apoptosis.
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