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The sensitivity of yeast and yeast-like cells to new lysosomotropic agents

Anna Krasowska1, Lucyna Chmielewska, Ryszard Adamski

  • 1Institute of Genetics and Microbiology, Wrocław University, Przybyszewskiego 63-77, 51-148 Wrocław, Poland. aniak@microb.uni.wroc.pl

Cellular & Molecular Biology Letters
|January 14, 2005
PubMed

Insights

The antifungal compounds DM-11 and DMAL-12s show species- and pH-dependent activity against yeast. DMAL-12s is more effective against Candida albicans, while both compounds impact Saccharomyces and Schizosaccharomyces differently.

Area of Science:

  • * Mycology
  • * Biochemistry
  • * Cell Biology

Background:

  • * The lysosomotropic action of compounds is crucial for antifungal drug development.
  • * Understanding species- and pH-dependent effects is key to targeting pathogenic yeasts like Candida albicans.
  • * Saccharomyces cerevisiae, Schizosaccharomyces pombe, and Candida albicans are model organisms for studying yeast biology and antifungal efficacy.

Purpose of the Study:

  • * To investigate the species- and pH-dependent lysosomotropic action of DM-11 and DMAL-12s against Saccharomyces cerevisiae, Schizosaccharomyces pombe, and Candida albicans.
  • * To elucidate the mechanisms of action, including intracellular acidification and morphological changes.
  • * To compare the efficacy of DM-11 and DMAL-12s across different yeast species and pH conditions.

Main Methods:

  • * Antifungal susceptibility testing at varying pH levels (6.0 and 8.0).
  • * Quinacrine accumulation assay to assess intracellular acidification.
  • * Morphological analysis using microscopy to observe cellular changes.
  • * Investigation of H+-ATPase sensitivity.

Main Results:

  • * DMAL-12s efficacy varied by species and pH; it was more effective against Candida albicans at pH 6.0 but less so against Saccharomyces cerevisiae and Schizosaccharomyces pombe.
  • * At pH 8.0, DMAL-12s strongly inhibited Saccharomyces cerevisiae growth, with marginal effects on Candida albicans, while Schizosaccharomyces pombe did not grow.
  • * DM-11 caused general intracellular acidification, whereas DMAL-12s showed marginal acidification. Morphological changes were observed, particularly in Schizosaccharomyces pombe, and lipid-like blisters appeared in vacuoles of Saccharomyces cerevisiae and Schizosaccharomyces pombe.

Conclusions:

  • * The antifungal activity of DM-11 and DMAL-12s is significantly influenced by yeast species and ambient pH.
  • * DMAL-12s demonstrates potential as a targeted antifungal agent, particularly against Candida albicans, with its efficacy modulated by pH.
  • * Further research is needed to understand the differential mechanisms of action and potential for drug resistance, especially concerning the H+-ATPase in Schizosaccharomyces pombe.

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