In vitro and in vivo anti-Candida activity of citral in combination with fluconazole

Miranda-Cadena, Katherine; Marcos‐Arias, Cristina; Perez-Rodriguez, Aitzol; Cabello-Beitia, Iván; Mateo, Estíbaliz; Sevillano, Elena; Madariaga, Lucila; Quindós, Guillermo; Eraso, Elena

doi:10.1080/20002297.2022.2045813

Cited by 7 publications

(9 citation statements)

References 45 publications

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“…Th e FIC value was 0.4, which indicates synergism between the compounds' activities [23]. Similar patterns were observed in the case of a combination of citral (0.25 mg/L) and fl uconazole (256 mg/L) against C. albicans UPV 15-157, with an FIC value of 0.5 [24].…”

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confidence: 53%

“…Note that there is no information in the literature on the synergism of the antimicrobial activity of microbial surfactants and EO of cinnamon and lemongrass. At the same time, there are works concerning the possibility of using a mixture of two or more EOs [19], a mixture of EO with antifungal drugs (mainly fl uconazole) [20][21][22][23][24], including cinnamon [21,22] and lemongrass [23,24]. Th e studies, the results of which are presented in [20][21][22][23][24], are quite relevant, es-pecially considering the spread of fl uconazoleresistant strains among representatives of Candida genus.…”

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confidence: 99%

“…At the same time, there are works concerning the possibility of using a mixture of two or more EOs [19], a mixture of EO with antifungal drugs (mainly fl uconazole) [20][21][22][23][24], including cinnamon [21,22] and lemongrass [23,24]. Th e studies, the results of which are presented in [20][21][22][23][24], are quite relevant, es-pecially considering the spread of fl uconazoleresistant strains among representatives of Candida genus. Th us, in the presence of cinnamon EO (MIC 62.5 μg/mL) in a mixture with fl uconazole (MIC 1000 μg/mL), a decrease in the order of the MIC of the antibiotic against C. albicans ATCC 10213 was observed, and the FIC value was 0.5 indicating their synergy [21].…”

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confidence: 99%

“…At the same time, the researchers note that EOs are able to destroy yeast biofi lms only at certain stages of their formation. Th us, citral, one of the main components of lemongrass EO, is quite eff ective for destroying yeast biofi lms at the early stages of formation (up to 24 hr) [24]. Th e destruction of C. albicans ATCC90028 biofi lm formed within 48 hr is possible only with a mixture of citral and fl uconazole (eff ective concentrations of citral and antifungal agent 0.139 and 0.08 mg/mL, respectively) [23].…”

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Synergistic Effect of Surfactants of Nocardia vaccinii IMV B-7405 and Essential Oils on Candida Genus Yeast

Pirog¹,

Kliuchka²,

Shevchuk³

et al. 2023

Mikrobiol. Z.

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The increase in the number of resistant strains of Candida genus representatives, capable of forming biofilms on various surfaces, stimulates the search for new, alternative methods of combating them, one of which is the use of compounds of natural origin, such as essential oils. However, at the same time, their concentration should be minimal, which is due to the ability of essential oils to cause severe damage of the human’s central nervous system and aspiration pneumonia. This leads to the necessity of searching for new methods to reduce the concentration of essential oils and at the same time to preserve their properties, in particular, by their use in a mixture with other antimicrobial agents, which can be microbial surfactants. Previously, it was found that the degree of yeast biofilm destruction under the action of Nocardia vaccinii IMV B-7405 surfactants dependson the nature of the growth substrate and is the highest in the presence of preparations synthesized on purified glycerol. Aim. To study the synergism of antifungal activity and the role in the destruction of biofilms of a mixture of Nocardia vaccinii IMV B-7405 surfactants synthesized on glycerol of different quality and essential oils. Methods. N. vaccinii IMV B-7405 was grown in a medium containing purified glycerol or waste from biodiesel production at a concentration of 2% (v/v) as carbon sources. The surfactants were extracted from the supernatant of cultural liquid by a modified Folch mixture. The antimicrobial activity of essential oils, surfactants, and their mixtures was determined by the index of the minimum inhibitory concentration. To assess the synergistic effect of a mixture of surfactants with essential oils, the fractional inhibitory concentration index was used. The degree of biofilm destruction (%) was determined as the difference between the cell adhesion in untreated and treated with surfactants, essential oil, or their mixture wells of the polystyrene microplates. Results. It was found that the surfactants synthesized by N. vaccinii IMV B-7405 on both purified glycerol and waste from biodiesel production showed synergistic antifungal activity in mixtures with cinnamon and lemongrass essential oils. Thus, the minimum inhibitory concentrations against Candida albicans D-6, Candida utilis BVS-65, and Candida tropicalis RE-2 of a mixture of surfactants synthesized on purified glycerol with cinnamon and lemongrass essential oils were 1.8—7.5 and 3.7— 15 μg/mL, respectively, and were lower than in the case of using surfactants (30-60 μg/mL), cinnamon or lemongrass essential oil (156—312 μg/mL) alone. The use of a mixture of surfactants obtained on waste from biodiesel production and cinnamon or lemongrass essential oils made it possible to reduce the minimum inhibitory concentrations of the latter against studied yeast test cultures by 14—56 times. At the same time, the index of fractional inhibitory concentration did not exceed 0.5, which indicates the synergism of the antifungal activity of the mixture of these compounds. The destruction of Candida yeast biofilms under the action of surfactants synthesized on both purified glycerol and waste from biodiesel production in a mixture with cinnamon or lemongrass essential oils reached 60—67 and 67—77%, respectively, which is an average of 25—35% higher compared to the use of each monopreparation separately. Conclusions. The results presented in this paper confirm the previously obtained data that N. vaccinii IMV B-7405 surfactants, synthesized on both traditional substrates and toxic industrial wastes, have antimicrobial and antiadhesive synergistic action with essential oils, which allows us to consider them as potential components of the so-called «antifungal locks» in the fight against of Candida genus representatives.

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confidence: 53%

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confidence: 99%

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confidence: 99%

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Synergistic Effect of Surfactants of Nocardia vaccinii IMV B-7405 and Essential Oils on Candida Genus Yeast

Pirog¹,

Kliuchka²,

Shevchuk³

et al. 2023

Mikrobiol. Z.

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“…The authors have also described that citral has the ability to damage the integrity of the plasma membrane through a mechanism that destabilizes the membrane itself, affecting its structure, blocking its synthesis, compromising its integrity and permeability and ultimately causing cell death [ 18 ]. Previous results obtained from in vitro and in vivo studies by our research group showed activity against other Candida species, such as C. albicans , C. glabrata and C. krusei [ 19 ].…”

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In Vitro and In Vivo Activity of Citral in Combination with Amphotericin B, Anidulafungin and Fluconazole against Candida auris Isolates

de-la-Fuente,

Guridi,

Jauregizar

et al. 2023

JoF

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Candida auris is an emerging fungal pathogen responsible for hospital outbreaks of invasive candidiasis associated with high mortality. The treatment of these mycoses is a clinical challenge due to the high resistance levels of this species to current antifungal drugs, and alternative therapeutic strategies are needed. In this study, we evaluated the in vitro and in vivo activities of combinations of citral with anidulafungin, amphotericin B or fluconazole against 19 C. auris isolates. The antifungal effect of citral was in most cases similar to the effect of the antifungal drugs in monotherapy. The best combination results were obtained with anidulafungin, with synergistic and additive interactions against 7 and 11 of the 19 isolates, respectively. The combination of 0.06 μg/mL anidulafungin and 64 μg/mL citral showed the best results, with a survival rate of 63.2% in Caenorhabditis elegans infected with C. auris UPV 17-279. The combination of fluconazole with citral reduced the MIC of fluconazole from > 64 to 1–4 μg/mL against 12 isolates, and a combination of 2 μg/mL fluconazole and 64 μg/mL citral was also effective in reducing mortality in C. elegans. Amphotericin B combined with citral, although effective in vitro, did not improve the activity of each compound in vivo.

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Monoterpenoid synergy: a new frontier in biological applications

Begh,

Khan,

Al Amin

et al. 2024

Naunyn-Schmiedeberg's Arch Pharmacol

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In vitro and in vivo anti-Candida activity of citral in combination with fluconazole

Cited by 7 publications

References 45 publications

Synergistic Effect of Surfactants of Nocardia vaccinii IMV B-7405 and Essential Oils on Candida Genus Yeast

Synergistic Effect of Surfactants of Nocardia vaccinii IMV B-7405 and Essential Oils on Candida Genus Yeast

In Vitro and In Vivo Activity of Citral in Combination with Amphotericin B, Anidulafungin and Fluconazole against Candida auris Isolates

Monoterpenoid synergy: a new frontier in biological applications

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