Synergistic antifungal effect of fluconazole combined with quorum sensing molecules of Candida parapsilosis against Trichophyton rubrum


Objective: The present study evaluated the synergistic interaction between a pure culture extract of Candida parapsilosis and fluconazole against Trichophyton rubrum.
Method: This study used clinical strains of C. parapsilosis from the Laboratory of Microbiology of the Medical School in São José do Rio Preto (FAMERP), Brazil. A 500-mL Inoculum prepared in Sabouraud Dextrose Broth was filtered through a 0.2 μm millipore membrane and separated using ethyl acetate as a counter-phase. The ethyl acetate phase was dried completely using a rotary evaporator and subsequently solubilized in sterile distilled water with 10% dimethyl sulfoxide (DMSO). Minimal Inhibitory Concentration (MIC) tests were performed for T. rubrum strains following the Clinical and Laboratory Standards Institute (CLSI) M38-A2 guidelines. After obtaining the MIC of the extract, a checkerboard trial with fluconazole was performed to evaluate the synergistic interaction with the extract based on the calculation of the fractional inhibitory concentration index (ICIF) = (MIC fluconazole in the mix / MIC fluconazole alone) + MIC extract in the mix / MIC extract isolated). The synergistic interaction was classified using the method described by Kumar et al., where values ≤ 0.5 indicate significant interactions.
Results: The results obtained for the MIC of C. parapsilosis extract against the T. rubrum strain and fluconazole in isolation were 1000 μg/mL and 8 μg/mL, respectively. However, when the extract was used in combination with fluconazole, the MIC value was 7.8 μg/mL and of fluconazole it was 0.25 μg/mL with an ICIF value of 0.03.
Conclusion: The extract of C. parapsilosis in isolation shows antifungal activity against T. rubrum, which may influence the laboratory diagnosis of mixed infections. Furthermore, the action of this extract is greater in association with an azole derivative, thus proving synergy. In the future, the isolation and identification of extract compounds may allow new therapeutic approaches in the control of fungal infections.