Micafungin is more active against Candida albicans biofilms with high metabolic activity

Marcos-Zambrano, Laura Judith; Escribano, Pilar; Vecchio, Marcela González del; Bouza, Emilio; Guinea, Jesús

doi:10.1093/jac/dku222

Cited by 16 publications

(8 citation statements)

References 18 publications

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“…Notably, micafungin is more active against biofilms with high metabolic activity at least in case of C. albicans (Marcos‐Zambrano et al . ). Furthermore, enhanced micafungin activity was observed against C. parapsilosis biofilm earlier by Shirazi and Kontoyiannis ().…”

Section: Discussionmentioning

confidence: 97%

Activity of exogenous tyrosol in combination with caspofungin and micafungin against Candida parapsilosis sessile cells

et al. 2017

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Section: Discussionmentioning

confidence: 97%

Activity of exogenous tyrosol in combination with caspofungin and micafungin against Candida parapsilosis sessile cells

et al. 2017

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“…The XTT colorimetric tetrazolium assay was used to evaluate the effects of laser treatments on total metabolic activity of C. albicans biofilm [ 23 , 24 ]. A commercial kit (AppliChem GmbH, Darmstadt, Germany) was employed following the manufacturer’s instructions.…”

Section: Methodsmentioning

confidence: 99%

Herpes simplex virus-1 entrapped in Candida albicans biofilm displays decreased sensitivity to antivirals and UVA1 laser treatment

Ascione

Sala

Mazaheri-Tehrani

et al. 2017

Ann Clin Microbiol Antimicrob

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BackgroundRecently, we published data suggesting a mutualistic relationship between HSV-1 and Candida. albicans; in particular: (a) HSV-1 infected macrophages are inhibited in their anti-Candida effector function and (b) Candida biofilm protects HSV-1 from inactivation. The present in vitro study is aimed at testing the effects of Candida biofilm on HSV-1 sensitivity to pharmacological and physical stress, such as antiviral drugs (acyclovir and foscarnet) and laser UVA1 irradiation. We also investigated whether fungus growth pattern, either sessile or planktonic, influences HSV-1 sensitivity to antivirals.MethodsMature Candida biofilms were exposed to HSV-1 and then irradiated with laser light (UVA1, 355 λ). In another set of experiments, mature Candida biofilm were co-cultured with HSV-1 infected VERO cells in the presence of different concentrations of acyclovir or foscarnet. In both protocols, controls unexposed to laser or drugs were included. The viral yield of treated and untreated samples was evaluated by end-point titration. To evaluate whether this protective effect might occur in relation with a different growth pattern, HSV-1 infected cells were co-cultured with either sessile or planktonic forms of Candida and then assessed for susceptibility to antiviral drugs.ResultsUVA1 irradiation caused a 2 Log reduction of virus yield in the control cultures whereas the reduction was only 1 Log with Candida biofilm, regardless to the laser dose applied to the experimental samples (50 or 100 J/cm2). The presence of biofilm increased the IC90 from 18.4–25.6 J/cm2. Acyclovir caused a 2.3 Log reduction of virus yield in the control cultures whereas with Candida biofilm the reduction was only 0.5 Log; foscarnet determined a reduction of 1.4 Log in the controls and 0.2 Log in biofilm cultures. Consequently, the ICs50 for acyclovir and foscarnet increased by 4- and 12-folds, respectively, compared to controls. When HSV-1 was exposed to either sessile or planktonic fungal cells, the antiviral treatments caused approximately the same weak reduction of virus yield.ConclusionsThese data demonstrate that: (1) HSV-1 encompassed in Candida biofilm is protected from inactivation by physical (laser) and pharmacological (acyclovir or foscarnet) treatments; (2) the drug antiviral activity is reduced at a similar extent for both sessile or planktonic Candida.

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“…Time-lapse recordings of yeast cell cultures under these experimental conditions showed that when budding cells started to grow, they blow up probably as a consequence of the loss of cell wall integrity, caused by their inability to synthetize new fungal wall ␤-glucan (data not shown). The MF effect depends on the metabolic status of the cells, since the biosynthesis of different structural components for the cell wall requires energy, which is partially obtained from mitochondrial activity (20). Thus, yeasts grown in a medium rich in nutrients with an active metabolism were sensitive to the echinocandin effect, in contrast to cells grown in YNB (Fig.…”

Section: Discussionmentioning

confidence: 99%

Micafungin Enhances the Human Macrophage Response to Candida albicans through β-Glucan Exposure

Guirao-Abad

Sánchez-Fresneda

Machado

et al. 2018

Antimicrob Agents Chemother

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Micafungin belongs to the antifungal family of echinocandins, which act as noncompetitive inhibitors of the fungal cell wall β-1,3-d-glucan synthase. Since is the most prevalent pathogenic fungus in humans, we study the involvement of micafungin in the modulation of the inflammatory response developed by human tissue macrophages against The MIC for micafungin was 0.016 μg/ml on the SC5314 standard strain. Micafungin induced a drastic reduction in the number of exponential SC5314 viable cells, with the fungicidal effect being dependent on the cellular metabolic activity. Notably, micafungin also caused a structural remodelling of the cell wall, leading to exposure of the β-glucan and chitin content on the external surface. At the higher doses used (0.05 μg/ml), the antifungal also induced the blowing up of budding yeasts. In addition, preincubation with micafungin before exposure to human tissue macrophages enhanced the secretion of tumor necrosis factor alpha (TNF-α), interleukin-17A (IL-17A), and IL-10 cytokines. Our results strongly suggest that in treatment with micafungin, in addition to having the expected toxic antifungal effect, it potentiates the immune response, improving the interaction and activation of human macrophages, probably through the unmasking of β-glucans on the cell wall surface.

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Micafungin is more active against Candida albicans biofilms with high metabolic activity

Abstract: Our study suggests that the metabolic activity of biofilm may have a role in future evaluations of micafungin for the eradication of C. albicans biofilms (e.g. the lock therapy approach).

Cited by 16 publications

References 18 publications

Activity of exogenous tyrosol in combination with caspofungin and micafungin against Candida parapsilosis sessile cells

Activity of exogenous tyrosol in combination with caspofungin and micafungin against Candida parapsilosis sessile cells

Herpes simplex virus-1 entrapped in Candida albicans biofilm displays decreased sensitivity to antivirals and UVA1 laser treatment

Micafungin Enhances the Human Macrophage Response to Candida albicans through β-Glucan Exposure

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