Abstract
The development of opportunistic pathogenic Candida strains insensitive to several classes of antifungals has emerged as a major health care problem during the last years. Combinational therapy of natural products (e.g., essential oils, EOs) with conventional antifungals has been suggested as a promising alternative to overcome this medical problem. The present study investigates the potential antifungal activity of EOs extracted from some selected medicinal plants, alone and in combination with two common conventional antifungals (fluconazole and amphotericin B) against four clinical Candida isolates. MIC assays indicated that EOs induced strong anticandidal activities with MIC values ranging from 0.162 to 4.950 mg/mL. The combination of amphotericin B with Thymus leptobotrys, Origanum compactum and Artemisia herba alba EOs provided a synergistic effect against C. krusei only, with MIC gain of four-fold, and additive effect against remaining strains (MIC gain = two-fold). Interesting synergistic interactions were observed by combining all studied EOs with fluconazole, with reduction rates of their MICs ranging from 16 to 512-fold. This synergistic effect was very pronounced with the combination of T. leptobotrys EO and fluconazole. These findings indicate that studied EOs can be used as anti-candidals in combination with antifungals, particularly fluconazole, to counteract the emergence of resistant Candida spp.
Highlights
The incidence of systemic fungal infections has been increasing significantly and currently affects millions of people worldwide [1,2,3]
Within 200 yeast species, Candida albicans has been described as the most common pathogen found in severe candidiasis infections, but other non-albicans Candida spp. such as C. glabrata, C. tropicalis, C. krusei, and C. parapsilosis are becoming increasingly insidious [6,7,8]
The essential oils (EOs) extracted by steam-distillation were found to be pale to dark yellow, except for A. leucotrichus EO which was blue, with yields ranging from (0.63 ± 0.05)% to
Summary
The incidence of systemic fungal infections has been increasing significantly and currently affects millions of people worldwide [1,2,3]. The current treatment of these candidiasis infections remains essentially based on the use of common polyenes (e.g., amphotericin B) and azole antifungals (e.g., fluconazole), mainly targeting ergosterol in the fungal cell membrane or its biosynthetic pathway [9,10,11]. The development of novel antifungal agents is becoming difficult and challenging due to the eukaryotic nature of Candida cells, which results in a limited number of drug targets. The synergy between conventional drugs and natural antimicrobial products has been described as an emerging strategy to minimize the effective doses of standard antifungals, minimizing their side effects and their related toxicity, while enhancing their biological efficacies [15,16]
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