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Background: Aureobasidin A is known as a cyclic depsipeptide antibiotic with toxic effects against yeasts such as Candida spp at low concentration. Combination therapy is used as a conventional treatment for fungal infections, especially drug-resistant cases. The current study aimed to investigate the combined effects of fluconazole and Aureobasidin A on fluconazole-resistant C. albicans isolates using broth microdilution method.
Materials & Methods: Antifungal activity of Aureobasidin A (AbA) compared to fluconazole against C. albicans ATCC 76615 strain was determined using the standardized broth microdilution method according to the Clinical and Laboratory Standards Institute (CLSI, document M27-Ed4) guidelines. The checkerboard method was used to test the combined effects of Aureobasidin A and fluconazole. The synergy, indifference, and antagonism were defined based on the fractional inhibitory concentration values below 0.5, 0.5-4, and more than 4 μg/mL, respectively.
Findings: MIC50 and MIC90 evaluations of Aureobasidin A and fluconazole were done at concentrations of 0.25-2 and 32-64 μg/mL against C. glabrata isolates, respectively. The synergy between fluconazole and Aureobasidin A was observed against Candida isolate. A reduced MIC was demonstrated against C. albicans isolate when fluconazole was combined with Aureobasidin A at 4 to 0.12 μg/mL concentrations.
Conclusion: The present study findings revealed that Aureobasidin A combined with fluconazole exhibited potent inhibitory effects against fluconazole-resistant C. albicans isolates. Further studies is recommended to investigate the synergistic effects of Aureobasidin A and other antifungal drugs.

 

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Backgrounds: Aspergillus fumigatus is a pathogen responsible for invasive aspergillosis and the main leading cause of death in immunosuppressed individuals. The present study aimed to evaluate the impact of eugenol-loaded chitosan nanoparticles on the expression of CYP51a and CYP51b, two well-known genes responsible for triazole drug resistance in A. fumigatus.
Materials & Methods: The minimum inhibitory concentration (MIC) of eugenol-loaded chitosan nanoparticles, chitosan, eugenol, and itraconazole was determined based on the Clinical and Laboratory Standards Institute M38-E3 method at concentrations of 4.6-2400, 11.7-12000, 2-2048, and 1-256 μg/mL, respectively. The expression of CYP51A and CYP51B was evaluated in A. fumigatus exposed to 0.5, 1, and 2× of MIC concentration of NPs and itraconazole using the real-time polymerase chain reaction.
Findings: The obtained results showed that eugenol-loaded chitosan nanoparticles sucessfully reduced A. fumigatus fungal growth at 300 μg/mL concentration. MIC of chitosan, eugenol, and itraconazole was measured to be 6000, 256, and 4 μg/mL, respectively. The results of real-time PCR also revealed that eugenol-loaded chitosan nanoparticles increased the expression of both CYP51A and CYP51B in a dose-dependent manner. The expression of fungal CYP51A and CYP51B at mRNA level was significantly increased 1.26, 1.93, and 3.1-fold as well as 1.2, 2.1, and 2.4-fold at concentrations of 150, 300, and 600 μg/mL, respectively (p<.05). However, it seems that the prepared nanoparticles had a lower impact on the expression of these genes compared to itraconazole.
Conclusion: Overall, these findings suggest that the treatment of A. fumigatus with eugenol-chitosan nanoparticles could increase the expression of the CYP51 gene, suggesting the anti-fungal property of these nanoparticles.

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Backgrounds: Allium cepa L. as a traditional medicine is a rich source of beneficial bioactive metabolites. In the present study, the effect of A. cepa ethanolic extract (EAC) was studied on Aspergillus fumigatus growth, ergosterol synthesis, gliotoxin production, and gliP gene expression.
Materials & Methods: The minimum inhibitory concentration (MIC) of EAC (125-4000 µg/mL) was determined against A. fumigatus isolates according to Clinical and Laboratory Standards Institute (CLSI) guidelines (M-38). Protease activity, gliotoxin production, cell membrane ergosterol content, ultrastructure, and gliP gene expression were evaluated in the fungus exposed to 0.5× MIC concentrations of EAC (1000 μg/mL) and fluconazole (FCZ: 64 μg/mL).
Findings: Ergosterol content was significantly reduced to 0.53 and 0.45 µg/mg in FCZ- and EAC-treated fungal cells, respectively (p< .001). The protease activity was significantly inhibited in both EAC- and FCZ-treated groups. The gliotoxin production was inhibited by 51.55 and 68.75% in the treated groups with FCZ and EAC, respectively. The expression of gliP in both EAC- and FCZ-treated A. fumigatus groups was significantly reduced by 0.40 and 0.53-fold, respectively (p< .05).
Conclusion: This study finding revealed that A. cepa ethanolic extract (EAC) effectively suppressed the growth and virulence factors of A. fumigatus, which could be attributed in part to its bioactive metabolites. Further studies are recommended to isolate and identify these metabolites as potential candidates for the development of antifungal drugs.