Antifungal activity of clotrimazole against Candida albicans depends on carbon sources, growth phase and morphology

Lydia Kasper, Pedro Miramon, Nadja Jablonowski, Stephanie Wisgott, Duncan Wilson, Sascha Brunke, Bernhard Hube

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Vulvovaginal candidiasis (VVC), a superficial infection predominantly caused by the pathogenic fungus Candida albicans, is frequently treated with clotrimazole. Some drug formulations contain lactate for improved solubility. Lactate may modify C. albicans physiology and drug sensitivity by serving as a carbon source for the fungus and/or affecting local pH. Here we explored the effects of lactate, in combination with pH changes, on C. albicans proliferation, morphology and clotrimazole sensitivity. Moreover, we determined the influence of growth phase and morphology per se on drug sensitivity. We show that utilisation of lactate as a carbon source does not promote fast fungal proliferation or filamentation. Lactate had no influence on clotrimazole-mediated killing of C. albicans in standard fungal cultivation media but had an additive effect on the fungicidal clotrimazole action under in vitro vagina-simulative conditions. Moreover, clotrimazole-mediated killing was growth-phase and morphology-dependent. Post-exponential cells were resistant to the fungicidal action of clotrimazole, while logarithmic cells were sensitive, and hyphae showed highest susceptibility. Finally, we show that treatment of preformed C. albicans hyphae with sub-lethal concentrations of clotrimazole induced a reversion to yeast phase growth. As C. albicans hyphae are considered the pathogenic morphology during mucosal infections, these data suggest that elevated fungicidal activity of clotrimazole against hyphae plus clotrimazole-induced hyphae-to-yeast reversion may help to dampen acute vaginal infections by reducing the relative proportion of hyphae and thus shifting to a non-invasive commensal-like population. In addition, lactate as an ingredient of clotrimazole formulations may potentiate clotrimazole killing of C. albicans in the vaginal microenvironment.
Original languageEnglish
Pages (from-to)714-723
Number of pages10
JournalJournal of Medical Microbiology
Volume64
Issue number7
Early online date1 Jul 2015
DOIs
Publication statusPublished - Jul 2015

Fingerprint

Clotrimazole
Candida albicans
Carbon
Hyphae
Growth
Lactic Acid
Fungi
Yeasts
Infection
Vulvovaginal Candidiasis
Drug Compounding
Vagina
Pharmaceutical Preparations
Solubility

Keywords

  • Candida Albicans
  • Carbon Sources
  • growth phase
  • morphology
  • drug sensitivity
  • pH

Cite this

Antifungal activity of clotrimazole against Candida albicans depends on carbon sources, growth phase and morphology. / Kasper, Lydia; Miramon, Pedro; Jablonowski, Nadja; Wisgott, Stephanie; Wilson, Duncan; Brunke, Sascha; Hube, Bernhard.

In: Journal of Medical Microbiology, Vol. 64, No. 7, 07.2015, p. 714-723.

Research output: Contribution to journalArticle

Kasper, L, Miramon, P, Jablonowski, N, Wisgott, S, Wilson, D, Brunke, S & Hube, B 2015, 'Antifungal activity of clotrimazole against Candida albicans depends on carbon sources, growth phase and morphology', Journal of Medical Microbiology, vol. 64, no. 7, pp. 714-723. https://doi.org/10.1099/jmm.0.000082
Kasper, Lydia ; Miramon, Pedro ; Jablonowski, Nadja ; Wisgott, Stephanie ; Wilson, Duncan ; Brunke, Sascha ; Hube, Bernhard. / Antifungal activity of clotrimazole against Candida albicans depends on carbon sources, growth phase and morphology. In: Journal of Medical Microbiology. 2015 ; Vol. 64, No. 7. pp. 714-723.
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abstract = "Vulvovaginal candidiasis (VVC), a superficial infection predominantly caused by the pathogenic fungus Candida albicans, is frequently treated with clotrimazole. Some drug formulations contain lactate for improved solubility. Lactate may modify C. albicans physiology and drug sensitivity by serving as a carbon source for the fungus and/or affecting local pH. Here we explored the effects of lactate, in combination with pH changes, on C. albicans proliferation, morphology and clotrimazole sensitivity. Moreover, we determined the influence of growth phase and morphology per se on drug sensitivity. We show that utilisation of lactate as a carbon source does not promote fast fungal proliferation or filamentation. Lactate had no influence on clotrimazole-mediated killing of C. albicans in standard fungal cultivation media but had an additive effect on the fungicidal clotrimazole action under in vitro vagina-simulative conditions. Moreover, clotrimazole-mediated killing was growth-phase and morphology-dependent. Post-exponential cells were resistant to the fungicidal action of clotrimazole, while logarithmic cells were sensitive, and hyphae showed highest susceptibility. Finally, we show that treatment of preformed C. albicans hyphae with sub-lethal concentrations of clotrimazole induced a reversion to yeast phase growth. As C. albicans hyphae are considered the pathogenic morphology during mucosal infections, these data suggest that elevated fungicidal activity of clotrimazole against hyphae plus clotrimazole-induced hyphae-to-yeast reversion may help to dampen acute vaginal infections by reducing the relative proportion of hyphae and thus shifting to a non-invasive commensal-like population. In addition, lactate as an ingredient of clotrimazole formulations may potentiate clotrimazole killing of C. albicans in the vaginal microenvironment.",
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AU - Kasper, Lydia

AU - Miramon, Pedro

AU - Jablonowski, Nadja

AU - Wisgott, Stephanie

AU - Wilson, Duncan

AU - Brunke, Sascha

AU - Hube, Bernhard

N1 - ACKNOWLEDGEMENTS This work was funded by Bayer Vital and supported by the resources and facilities at the Hans Knoell Institute Jena, Germany. We thank Melanie Kahl for excellent assistance with the laboratory work.

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N2 - Vulvovaginal candidiasis (VVC), a superficial infection predominantly caused by the pathogenic fungus Candida albicans, is frequently treated with clotrimazole. Some drug formulations contain lactate for improved solubility. Lactate may modify C. albicans physiology and drug sensitivity by serving as a carbon source for the fungus and/or affecting local pH. Here we explored the effects of lactate, in combination with pH changes, on C. albicans proliferation, morphology and clotrimazole sensitivity. Moreover, we determined the influence of growth phase and morphology per se on drug sensitivity. We show that utilisation of lactate as a carbon source does not promote fast fungal proliferation or filamentation. Lactate had no influence on clotrimazole-mediated killing of C. albicans in standard fungal cultivation media but had an additive effect on the fungicidal clotrimazole action under in vitro vagina-simulative conditions. Moreover, clotrimazole-mediated killing was growth-phase and morphology-dependent. Post-exponential cells were resistant to the fungicidal action of clotrimazole, while logarithmic cells were sensitive, and hyphae showed highest susceptibility. Finally, we show that treatment of preformed C. albicans hyphae with sub-lethal concentrations of clotrimazole induced a reversion to yeast phase growth. As C. albicans hyphae are considered the pathogenic morphology during mucosal infections, these data suggest that elevated fungicidal activity of clotrimazole against hyphae plus clotrimazole-induced hyphae-to-yeast reversion may help to dampen acute vaginal infections by reducing the relative proportion of hyphae and thus shifting to a non-invasive commensal-like population. In addition, lactate as an ingredient of clotrimazole formulations may potentiate clotrimazole killing of C. albicans in the vaginal microenvironment.

AB - Vulvovaginal candidiasis (VVC), a superficial infection predominantly caused by the pathogenic fungus Candida albicans, is frequently treated with clotrimazole. Some drug formulations contain lactate for improved solubility. Lactate may modify C. albicans physiology and drug sensitivity by serving as a carbon source for the fungus and/or affecting local pH. Here we explored the effects of lactate, in combination with pH changes, on C. albicans proliferation, morphology and clotrimazole sensitivity. Moreover, we determined the influence of growth phase and morphology per se on drug sensitivity. We show that utilisation of lactate as a carbon source does not promote fast fungal proliferation or filamentation. Lactate had no influence on clotrimazole-mediated killing of C. albicans in standard fungal cultivation media but had an additive effect on the fungicidal clotrimazole action under in vitro vagina-simulative conditions. Moreover, clotrimazole-mediated killing was growth-phase and morphology-dependent. Post-exponential cells were resistant to the fungicidal action of clotrimazole, while logarithmic cells were sensitive, and hyphae showed highest susceptibility. Finally, we show that treatment of preformed C. albicans hyphae with sub-lethal concentrations of clotrimazole induced a reversion to yeast phase growth. As C. albicans hyphae are considered the pathogenic morphology during mucosal infections, these data suggest that elevated fungicidal activity of clotrimazole against hyphae plus clotrimazole-induced hyphae-to-yeast reversion may help to dampen acute vaginal infections by reducing the relative proportion of hyphae and thus shifting to a non-invasive commensal-like population. In addition, lactate as an ingredient of clotrimazole formulations may potentiate clotrimazole killing of C. albicans in the vaginal microenvironment.

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