Saccharomyces cerevisiae and Candida albicans Yeast Cells Labeled with Fe(III) Complexes as MRI Probes

Abstract

The development of MRI probes is of interest for labeling antibiotic-resistant fungal infections based on yeast. Our work showed that yeast cells can be labeled with high-spin Fe(III) complexes to produce enhanced T2 water proton relaxation. These Fe(III)-based macrocyclic complexes contained a 1,4,7-triazacyclononane framework, two pendant alcohol groups, and either a non-coordinating ancillary group and a bound water molecule or a third coordinating pendant. The Fe(III) complexes that had an open coordination site associated strongly with Saccharomyces cerevisiae upon incubation, as shown by screening using Z-spectra analysis. The incubation of one Fe(III) complex with either Saccharomyces cerevisiae or Candida albicans yeast led to an interaction with the β-glucan-based cell wall, as shown by the ready retrieval of the complex by the bidentate chelator called maltol. Other conditions, such as a heat shock treatment of the complexes, produced Fe(III) complex uptake that could not be reversed by the addition of maltol. Appending a fluorescence dye to Fe(TOB) led to uptake through secretory pathways, as shown by confocal fluorescence microscopy and by the incomplete retrieval of the Fe(III) complex by the maltol treatment. Yeast cells that were labeled with these Fe(III) complexes displayed enhanced water proton T2 relaxation, both for S. cerevisiae and for yeast and hyphal forms of C. albicans.