Abstract
Candidiasis caused by the fluconazole-resistant opportunistic pathogen Candida albicans is an intractable clinical problem that threatens immunocompromised or normal individuals. The most common mechanism of fluconazole resistance in C. albicans is the failure of cells to accumulate the drug due to increased expression of the efflux proteins encoded by the CDR1, CDR2, and MDR1 genes. Because the number of current antifungal drugs is limited, it is necessary to develop new therapeutic strategies. This study aimed to evaluate the antifungal activity of Thai Cajuput oil, its synergism with fluconazole, and its effect on efflux-pump gene expression in fluconazole-resistant C. albicans clinical isolates. Thus, we first detected the efflux-pump genes in fourteen resistant strains by PCR. The frequencies of the CDR1, CDR2, and MDR1 genes were 68.75%, 62.5%, and 87.5%, respectively, and these efflux-pump genes were distributed in three distinct patterns. Subsequently, the antifungal activity of Thai Cajuput oil was assessed by broth macrodilution and its synergism with fluconazole was evaluated by the checkerboard assay. The changes in the expression levels of CDR1, CDR2, and MDR1 after treatment with Thai Cajuput oil were analyzed by qRT-PCR. The MICs and MFCs of Thai Cajuput oil ranged from 0.31 to 1.25 μl/ml and 0.63 to 1.25 μl/ml, respectively, and its activity was defined as fungicidal activity. The MICs of the combination of Thai Cajuput oil and fluconazole were much lower than the MICs of the individual drugs. Interestingly, sub-MICs of Thai Cajuput oil significantly reduced the MDR1 expression level in resistant strains (P < 0.05). Our study suggests that Thai Cajuput oil can be used to create new potential combination therapies to combat the antifungal resistance of C. albicans.
Highlights
Candidiasis is one of the most important fungal infections caused by Candida species; these infections pose a challenging threat to human health and affect millions of individuals
According to efflux-pump gene screening among sixteen resistant strains by PCR, efflux-pump genes were detected in fourteen resistant strains (87.5%) but not in two resistant strains (12.5%). e PCR products of the CDR1, CDR2, and MDR1 genes after separation by electrophoresis on an agarose gel are shown in Figure 1. e presence of the MDR1 gene showed the highest frequency among the fourteen resistant strains. e frequencies of the CDR1, CDR2, and MDR1 genes were 68.75%, 62.5%, and 87.5%, respectively
According to the minimum fungicidal concentration (MFC)/ minimum inhibitory concentration (MIC) ratio calculation, the ratios were within the range of 1 to 2, and the antifungal activity of ai Cajuput oil was defined as fungicidal activity
Summary
Candidiasis is one of the most important fungal infections caused by Candida species; these infections pose a challenging threat to human health and affect millions of individuals. More than 17 species of Candida are responsible for causing both superficial and life-threatening systemic mycoses, and of these, Candida albicans is a major fungal pathogen accounting for invasive candidiasis and is the most common cause of nosocomial infections. C. albicans can undergo a transition from a commensal to pathogenic form in immunocompromised hosts/normal individuals and function as an opportunistic pathogen. The growth of Candida biofilms on medical devices has emerged as a major challenge in hospital settings, leading to secondary fungal infections and resulting in morbidity and mortality of immunocompromised individuals (including HIV-infected patients, transplant recipients, chemotherapy patients, diabetes patients, and lowbirth-weight infants) [1, 2]
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