Analysis of the biological activity of a novel 24-membered macrolide JBIR-19 in Saccharomyces cerevisiae by the morphological imaging program CalMorph

FEMS Yeast Res. 2012 May;12(3):293-304. doi: 10.1111/j.1567-1364.2011.00770.x. Epub 2012 Jan 3.

Abstract

To investigate the biological activity of a novel 24-membered macrolide compound, JBIR-19, isolated from the culture broth of the entomopathogenic fungus Metarhizium sp. fE61, morphological changes in yeast cells were examined using the automated image-processing program CalMorph. Principal components analysis was used to elucidate dynamic changes in the phenotypes, revealing two independent effects of JBIR-19 in yeast cells: bud elongation and increased size of the actin region. Using a fitness assay, we identified the genes required for robust growth in the presence of JBIR-19. Among these were CCW12, YLR111W, and DHH1, which are also involved in abnormal bud morphology. Based on these results and others, we predict intracellular targets of JBIR-19 and its functional interactions.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Antifungal Agents / metabolism
  • Antifungal Agents / pharmacology
  • Image Processing, Computer-Assisted / methods*
  • Macrolides / metabolism
  • Macrolides / pharmacology*
  • Metarhizium / metabolism
  • Microscopy, Fluorescence
  • Phenotype
  • Principal Component Analysis
  • Saccharomyces cerevisiae / cytology*
  • Saccharomyces cerevisiae / drug effects*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Software*

Substances

  • Actins
  • Antifungal Agents
  • JBIR-19
  • Macrolides
  • Saccharomyces cerevisiae Proteins