Enhancing the Antifungal Efficacy of Fluconazole with a Diterpene: Abietic Acid as a Promising Adjuvant to Combat Antifungal Resistance in Candida spp.

The increasing antifungal resistance rates against conventional drugs reveal the urgent need to search for new therapeutic alternatives. In this context, natural bioactive compounds have a critical role in antifungal drug development. Since evidence demonstrates that abietic acid, a diterpene found in Pinus species, has significant antimicrobial properties, this study aimed to evaluate the antifungal activity of abietic acid against Candida spp and its ability to potentiate the activity of fluconazole. Abietic acid was tested both individually and in combination with fluconazole against Candida albicans (CA INCQS 40006), Candida krusei (CK INCQS 40095), and Candida tropicalis (CT INCQS 40042). The microdilution method was used to determine the IC50 and the cell viability curve. Minimum Fungicidal Concentration (MFC) was determined by subculture in a solid medium. The plasma membrane permeability was measured using a fluorescent SYTOX Green probe. While the IC50 of the drugs alone ranged between 1065 and 3255 µg/mL, the IC50 resulting from the combination of abietic acid and fluconazole ranged between 7563 and 160.1 µg/mL. Whether used in combination with fluconazole or isolated, abietic acid exhibited Minimum Fungicidal Concentration (MFC) values exceeding 1024 µg/mL against Candida albicans, Candida krusei and Candida tropicalis. However, it was observed that the antifungal effect of fluconazole was enhanced when used in combination with abietic acid against Candida albicans and Candida tropicalis. These findings suggest that while abietic acid alone has limited inherent antifungal activity, it can enhance the effectiveness of fluconazole, thereby reducing antifungal resistance.

Lectins ConA and ConM extracted from Canavalia ensiformis (L.) DC and Canavalia rosea (Sw.) DC inhibit planktonic Candida albicans and Candida tropicalis.

Lectins participate in the defense against microorganisms and in signaling the damage caused by pathogens to the cell surface and/or intracellular in plants. This study aims to analyze the antifungal potential of lectins extracted from seeds of Canavalia ensiformis (L.) DC and Canavalia rosea (Sw.) DC, against Candida albicans and Candida tropicalis. The antimicrobial tests were performed by microdilution against Candida spp. The test to verify the combined lectin/fluconazole effect was performed using subinhibitory concentrations of lectins and with antifungal ranging from 0.5 to 512 µg/mL. The ability to inhibit the morphological transition of Candida spp. was evaluated by microcultivation in a moist chamber. The results of the minimum inhibitory concentration revealed no antifungal activity against the tested strains. However, lectins modified the action of fluconazole, reducing the IC50 of the drug against C. albicans. Lectins were also able to discretely modulate the morphological transition of the tested strains.

Anti-Candida Properties of Gossypium hirsutum L.: Enhancement of Fungal Growth, Biofilm Production and Antifungal Resistance.

(1) Background: Candida is a genus of yeasts with notable pathogenicity and significant ability to develop antimicrobial resistance. Gossypium hirsutum L., a medicinal plant that is traditionally used due to its antimicrobial properties, has demonstrated significant antifungal activity. Therefore, this study investigated the chemical composition and anti-Candida effects of aqueous (AELG) and hydroethanolic (HELG) extracts obtained from the leaves of this plant. (2) Methods: The extracts were chemically characterized by UPLC-QTOF-MS/MS, and their anti-Candida activities were investigated by analyzing cell viability, biofilm production, morphological transition, and enhancement of antifungal resistance. (3) Results: The UPLC-QTOF-MS/MS analysis revealed the presence of twenty-one compounds in both AELG and HELG, highlighting the predominance of flavonoids. The combination of the extracts with fluconazole significantly reduced its IC50 values against Candida albicans INCQS 40006, Candida tropicalis INCQS 40042, and C. tropicalis URM 4262 strains, indicating enhanced antifungal activity. About biofilm production, significant inhibition was observed only for the AELG-treated C. tropicalis URM 4262 strain in comparison with the untreated control. Accordingly, this extract showed more significant inhibitory effects on the morphological transition of the INCQS 40006 and URM 4387 strains of C. albicans (4) Conclusions: Gossypium hirsutum L. presents promising antifungal effects, that may be potentially linked to the combined activity of chemical constituents identified in its extracts.

GC/MS analysis and antimicrobial activity of the Piper mikanianum (Kunth) Steud. essential oil.

The Piper mikanianum species were investigated by the antimicrobial potential and chemical composition. Chemical analysis was performed by gas chromatography coupled to mass spectrometry (GC/MS). The Minimum Inhibitory Concentration (MIC) as well as the 50% Inhibitory Concentration against Candida strains were determined by microdilution. The effect of the drug-oil combination was also evaluated to verify possible synergism. The Minimum Fungicidal Concentration (MFC) was evaluated by subculturing the microdilution in Petri dishes and the anti-pleomorphism potential of the oil was tested in humid chambers. Chemical analysis revealed safrol as the major compound. The results from the intrinsic activity evaluation of the oil did not reveal a clinical importance, however, it presented a synergistic effect when associated with gentamicin against the multidrug resistant E. coli strain and when associated with fluconazole against fungal strains. Moreover, the oil possessed a fungistatic effect. Total inhibition of filamentous structures occurred in both Candida species in the anti-virulence test. The P. mikanianum essential oil showed a potentiating activity of drugs for which resistance exists and an inhibitory effect of one of the main virulence factors of the Candida genus, morphological transition, which has been previously shown to be responsible for causing invasive infections in human tissues.