Antifungal Activity of Thai Cajuput Oil and Its Effect on Efflux-Pump Gene Expression in Fluconazole-Resistant Candida albicans Clinical Isolates

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.

Essential Oils as a Good Weapon against Drug-Resistant Candida auris

“…The EO of Melaleuca quinquenervia (niaouli oil) was found to be effective against bacteria as well as a range of fungi, including C. albicans [ 22 ]. Additionally, Keereedach et al found that Melaleuca cajuputi (cajeput oil) had potent antifungal activity against clinical isolates of C. albicans resistant to FLC, where it was able to reduce the MIC of FLC and reduce the expression level of MDR1 (an important gene that plays a role in resistance to azole drugs in C. albicans ) [ 23 ]. However, so far, there are few studies regarding the effect of niaouli and cajeput oils in Candida species, with this being the first study to use both oils in Candida biofilms.…”

Vapor-Phase of Essential Oils as a Promising Solution to Prevent Candida Vaginal Biofilms Caused by Antifungal Resistant Strains

“…In fact, the tea tree EO was found to increase yeast cell permeability and membrane fluidity and to inhibit the acidification of the medium [ 46 ]. Moreover, Keereedach, Hrimpeng, and Boonbumrung recently demonstrated that the cajeput EO has an antifungal effect on fluconazole-resistant C. albicans isolates [ 47 ]. These investigators showed that the cajeput EO reduced the expression level of the C. albicans MDR1 gene, which encodes the multidrug resistance protein 1 [ 47 ].…”

“…Moreover, Keereedach, Hrimpeng, and Boonbumrung recently demonstrated that the cajeput EO has an antifungal effect on fluconazole-resistant C. albicans isolates [ 47 ]. These investigators showed that the cajeput EO reduced the expression level of the C. albicans MDR1 gene, which encodes the multidrug resistance protein 1 [ 47 ]. Of note, the antifungal activity of EOs has been shown to be influenced by several factors, such as the original species, geographic and climatic conditions, the biological and physical–chemical properties of the soil, and storage conditions [ 48 ].…”

Chemical Composition and Antimicrobial Potential of Essential Oil of Acritopappus confertus (Gardner) R.M.King & H.Rob. (Asteraceae)

“…As fluconazole inhibits the synthesis of ergosterol by inhibiting the 14α-demethylase enzyme that is present in the cell membrane, its action will only occur with its presence in the intracellular environment. Therefore, an inhibition of the efflux pump genes is necessary, which may be the possible targets of the essential oil under study [ 54 ].…”