Synergistic Antifungal Effect of aspirin Combined with Fluconazole against azole-resistant oral Candida glabrata isolates

Azole compounds have been a treatment option for Candida glabrata infections. However, azole resistance can occur through different mechanisms such as alterations in ERG۱۱ (lanosterol ۱۴α-demethylase). Aspirin (ASA), a non-steroidal anti-inflammatory drug, showed antimicrobial activity against Candida. The purpose of this study was to evaluate the synergistic effect of ASA as an anti-inflammatory drug with the fluconazole on the azole-resistant C. glabrata isolates. In the cross-sectional study, a total of ۶۰ oral samples were collected from the school of dentistry, Tehran University of medical sciences. After confirmation of fungal isolates, template DNA was extracted and PCR for detection of Erg۱۱ gene by specific primers was performed in all Fluconazole-resistant isolates. MIC for ASA was determined using broth dilution method in ۹۶‐well plates. RNA was extracted and cDNA synthesized according to the Omniscript RT kit instructions. The effect of ASA in the treated and non-treated groups on ERG۱۱ gene expression was determined by Real-Time PCR technique. Out of ۶۰ collected samples, ۱۲ (۲۰%) C. glabrata were isolated. All of these isolates were resistant to fluconazole and carried ERG۱۱ genes. Real-time PCR results showed that the combination of ASA with fluconazole reduced ERG۱۱ gene expression. It is concluded that, treatment of candidal infections with ASA significantly reduced resistance in to azole compounds by down expression of ERG۱۱ gene, suggesting that an NSAID might be useful for azole-resistance candidal infections.

Keywords:

Candida glabrata , Fluconazole , Aspirin , ERG۱۱ , Real-time PCR