The resistance of Candida albicans to azole drugs represents a great global challenge. This study investigates the potential fungicidal effects of atorvastatin (ATO) combinations with fluconazole (FLU), itraconazole (ITR), ketoconazole (KET) and voriconazole (VOR) against thirty-four multidrug-resistant (MDR) C. albicans using checkerboard and time-kill methods. Results showed that 94.12% of these isolates were MDR to ≥ two azole drugs, whereas 5.88% of them were susceptible to azole drugs. The tested isolates exhibited high resistance rates to FLU (58.82%), ITR (52.94%), VOR (47.06%) and KET (35.29%), whereas only three representative (8.82%) isolates were resistant to all tested azoles. Remarkably, the inhibition zones of these isolates were increased at least twofold with the presence of ATO, which interacted in a synergistic (FIC index ≤ 0.5) manner with tested azoles. In silico docking study of ATO and the four azole drugs were performed against the Lanosterol 14-alpha demethylase enzyme (ERG11) of C. albicans . Results showed that the mechanism of action of ATO against C. albicans is similar to that of azole compounds, with a docking score (−4.901) lower than azole drugs (≥5.0) due to the formation a single H-bond with Asp 225 and a pi–pi interaction with Thr 229. Importantly, ATO combinations with ITR, VOR and KET achieved fungicidal effects (≥ 3 Log 10 cfu/ml reduction) against the representative isolates, whereas a fungistatic effect (≤ 3 Log 10 cfu/ml reduction) was observed with FLU combination. Thus, the combination of ATO with azole drugs could be promising options for treating C. albicans infection.

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Background: Benzalkonium Chloride (BC) is widely used in hospitals, industry and cosmetics. Adaptation of Pseudomonas aeruginosa to BC was increased. This adaptation may lead to the emergence of cross-resistance to other disinfectants and antibiotics. Little attention has been focused on the resistant mechanisms. Aim of Study: Examination of mutations in the Quinoloneresistance-Determining Region (QRDR) of GyrA and ParC genes and alterations of Outer-Membrane Proteins (OMPs) in Benzalkonium Chloride (BC)-adapted Pseudomonas aeruginosa isolates. Material and Methods: GyrA and ParC genes of the BCadapted P. aeruginosa isolate and the wild-type strain ATCC 15442 were amplified by Polymerase-Chain-Reaction (PCR) and sequenced. OMPs of these isolates were also analyzed by Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis (SDS-PAGE) in the presence and absence of permeabilizer disodium Ethylenediamine-Tetraacetate (EDTA) to investigate the variations. Results: The results manifested a single mutation in both GyrA (Thr-83-Ile) and ParC (Ser-87-Leu). In SDS-PAGE, one band with molecular weight of 52.23kDa was detected in all samples.

The resistance of Candida albicans to azole drugs represents the great global challenge. This study investigates the potential fungicidal effects of atorvastatin (ATO) combinations with fluconazole (FLU), itraconazole (ITR), ketoconazole (KET) and voriconazole (VOR) against thirty-four multidrug-resistant (MDR) C. albicans using checkerboard and time-kill methods. Results showed that 94.12% of these isolates were MDR to ≥ two azole drugs, whereas 5.88% of them were susceptible to azole drugs. The tested isolates exhibited high resistance rates to FLU (58.82%), ITR (52.94%), VOR (47.06 %) and KET (35.29 %), whereas only three representative (8.82%) isolates were resistant to all tested azoles. Remarkably, the inhibition zones of these isolates were increased at least two-fold with the presence of ATO, which interacted in a synergistic (FIC index ≤ 0.5) manner with tested azoles. In silico docking study of ATO and the four azole drugs were performed against the Lanosterol 14-alpha demethylase enzyme (ERG11) of C. albicans. Results showed that the mechanism of action of ATO against C. albicans is similar to that of azole compounds, with docking score (-4.901) lower than azole drugs (> - 5.0) due to the formation a single H-bond with Asp 225 and a pi-pi interaction with Thr 229. Importantly, ATO combinations with ITR, VOR and KET achieved fungicidal effects (≥ 3 Log10 cfu/ml reduction) against the representative isolates, whereas a fungistatic effect (≤ 3 Log10 cfu/ml reduction) was observed with FLU combination. Thus, the combination of ATO with azole drugs could be promising options for treating C. albicans infection.