Minimum inhibitory concentrations of amphotericin B, azoles and caspofungin against<i>Candida</i>species are reduced by farnesol

Cordeiro, Rossana de Aguiar; Teixeira, Carlos Eduardo Cordeiro; Brilhante, Raimunda Sâmia Nogueira; Castelo-Branco, Débora de Souza Collares Maia; Paiva, Manoel A. N.; Leite, João Jaime Giffoni; Lima, Daniel Teixeira; Monteiro, André Jalles; Sidrim, José Júlio Costa; Rocha, Marcos Fábio Gadelha

doi:10.3109/13693786.2012.692489

Cited by 93 publications

(64 citation statements)

References 26 publications

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“…More recently, many studies have described the activity of farnesol against different species of fungi (15)(16)(17)(18). In this study, for the first time, the antifungal activity of farnesol against the primary pathogen C. posadasii, the causative agent of coccidioidomycosis, was investigated.…”

Section: Discussionmentioning

confidence: 99%

“…Derengowski et al demonstrated the in vitro activity of farnesol against the dimorphic fungus Paracoccidioides brasiliensis, which presented an average MIC of 25 M (16). Moreover, recent studies from our group performed with the species Cryptococcus neoformans and C. gattii showed MIC values ranging from 0.29 to 75 M for both species (17), while the farnesol MICs ranged from 9.37 to 150 M against different Candida species (18).…”

Section: Discussionmentioning

confidence: 99%

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Effect of Farnesol on Growth, Ergosterol Biosynthesis, and Cell Permeability in Coccidioides posadasii

Brilhante

Lima

Caetano

et al. 2013

Antimicrob Agents Chemother

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Coccidioidomycosis is a systemic mycosis caused by the dimorphic fungi Coccidioides spp. The treatment for chronic and/or disseminated coccidioidomycosis can be prolonged and complicated. Therefore, the search for new drugs is necessary. Farnesol is a precursor in the sterol biosynthesis pathway that has been shown to present antifungal activity. Thus, the objective of this study was to evaluate the in vitro antifungal activity of farnesol alone and in combination with antifungal agents against clinical and environmental strains of Coccidioides posadasii as well as to determine their effect on the synthesis of ergosterol and on cell permeability. This study employed the broth macrodilution method to determine the MIC of farnesol against 18 strains of C. posadasii. Quantification of ergosterol was performed with 10 strains of C. posadasii after exposure to subinhibitory concentrations of farnesol. Finally, the activity of farnesol was evaluated in the presence of osmotic stress, induced by the addition of NaCl to the culture medium, during the susceptibility tests. The results showed that farnesol exhibited low MICs (ranging from 0.00171 to 0.01369 mg/liter) against all tested strains. The combination of farnesol with the antifungals showed synergistic effects (fractional inhibitory concentration index [FICI] < 0.5). As for the ergosterol quantification, it was observed that exposure to subinhibitory concentrations of farnesol decreased the amount of ergosterol extracted from the fungal cells. Furthermore, farnesol also showed lower MIC values when the strains were subjected to osmotic stress, indicating the action of this compound on the fungal membrane. Thus, due to the high in vitro antifungal activity, this work brings perspectives for the performance of in vivo studies to further elucidate the effects of farnesol on the host cells.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effect of Farnesol on Growth, Ergosterol Biosynthesis, and Cell Permeability in Coccidioides posadasii

Brilhante

Lima

Caetano

et al. 2013

Antimicrob Agents Chemother

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“…In addition, farnesol is a quorum-sensing molecule of Candida albicans, controlling factors such as density, cell morphogenesis (Hornby et al, 2001) and biofilm formation (Ramage et al, 2002). Currently, its potential antifungal effects have been reported against different fungal pathogens Cordeiro et al, 2013). In this context, the present study evaluated the in vitro inhibitory effect of farnesol against the dimorphic fungus H. capsulatum var.…”

Section: Discussionmentioning

confidence: 99%

Histoplasma capsulatum in planktonic and biofilm forms: in vitro susceptibility to amphotericin B, itraconazole and farnesol

Brilhante

Lima

Marques

et al. 2015

Journal of Medical Microbiology

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It is believed that most microbial infections are caused by pathogens organized in biofilms. Recently, it was shown that the dimorphic fungus Histoplasma capsulatum, estimated to be the most common cause of fungal respiratory diseases, is also able to form biofilm. Although the antifungal therapy commonly used is effective, refractory cases and recurrences have been reported. In the search for new compounds with antimicrobial activity, the sesquiterpene farnesol has gained prominence for its antifungal action. This study aimed to evaluate the in vitro susceptibility of H. capsulatum var. capsulatum to the antifungal agents itraconazole and amphotericin B, and farnesol alone and combined, as well as to determine the in vitro antifungal activity of these compounds against biofilms of this pathogen. The results show that farnesol has antifungal activity against H. capsulatum in the yeast and filamentous phases, with MIC values ranging from 0.0078 to 0.00312 mM. A synergistic effect (fractional inhibitory concentration index ¡0.5) between itraconazole and farnesol was found against 100 and 83.3 % of the isolates in yeast and mycelial forms, respectively, while synergism between amphotericin B and farnesol was only observed against 37.5 and 44.4 % of the isolates in yeast and filamentous forms, respectively. Afterwards, the antifungal drugs, itraconazole and amphotericin B, and farnesol alone, and the combination of itraconazole and farnesol, were tested against mature biofilms of H. capsulatum, through XTT (2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium hydroxide) metabolic assay, and the itraconazole and amphotericin B showed lower antibiofilm activity when compared to farnesol alone and farnesol combined with itraconazole. In conclusion, farnesol showed promising results as an antifungal agent against H. capsulatum and also showed adjuvant action, especially when combined with itraconazole, increasing the fungal susceptibility to this drug.

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“…Brilhante et al showed that farnesol had an inhibiting activity alone and in combination with antifungal agents against strains of dimorphic fungi from the genus Coccidioides and against Candida spp. clinical isolates [4,5]. Nerolidol shows a toxic effect against, inter alia, Salmonella enterica, Staphylococcus aureus, Escherichia coli and Aspergillus niger, and increases the antibacterial activity of antibiotics [6,7].…”

Section: Figurementioning

confidence: 99%

“…Structures of geranyl acetone (1); nerolidol (2); farnesal (3); farnesol (4) and farnesyl acetate (5).…”

Section: Figurementioning

confidence: 99%

Selected Compounds Structurally Related to Acyclic Sesquiterpenoids and Their Antibacterial and Cytotoxic Activity

et al. 2015

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By implementing a common and industrially used method, 30 compounds which are structurally related to geranyl acetone, nerolidol, farnesal, farnesol and farnesyl acetate were obtained. Their antimicrobial activity against Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii bacteria was investigated. Pharmacophore models were proposed based on the obtained results and 3D QSAR modelling. Cytotoxic effects against mainly human immortalised and normal cell lines of different origin (malignant melanoma MeWo, colorectal adenocarcinoma HT29, promyelocytic leukemia HL60, gingival fibroblasts HFIG, skin keratinocytes HaCaT and rat small intestine epithelium IEC6) were examined. The odour descriptions of newly synthesised compounds are given.

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Minimum inhibitory concentrations of amphotericin B, azoles and caspofungin againstCandidaspecies are reduced by farnesol

Cited by 93 publications

References 26 publications

Effect of Farnesol on Growth, Ergosterol Biosynthesis, and Cell Permeability in Coccidioides posadasii

Effect of Farnesol on Growth, Ergosterol Biosynthesis, and Cell Permeability in Coccidioides posadasii

Histoplasma capsulatum in planktonic and biofilm forms: in vitro susceptibility to amphotericin B, itraconazole and farnesol

Selected Compounds Structurally Related to Acyclic Sesquiterpenoids and Their Antibacterial and Cytotoxic Activity

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