Scientific
Publications - Work Done by Microbiology Reader Bioscreen C
Jess Allen, Hazel M. Davey, David Broadhurst, Jem J. Rowland, Stephen G.
Oliver, and Douglas B. Kell,
Discrimination of Modes of Action of Antifungal Substances by Use of
Metabolic Footprinting, Applied and Environmental Microbiology, October
2004, p. 6157-6165, Vol. 70, No. 10
ABSTRACT
Diploid cells of Saccharomyces cerevisiae were grown under controlled
conditions with a Bioscreen instrument, which permitted the
essentially continuous registration of their growth via optical
density measurements. Some cultures were exposed to concentrations of
a number of antifungal substances with different targets or modes of
action (sterol biosynthesis, respiratory chain, amino acid synthesis,
and the uncoupler). Culture supernatants were taken and analyzed for
their "metabolic footprints" by using direct-injection mass
spectrometry. Discriminant function analysis and hierarchical cluster
analysis allowed these antifungal compounds to be distinguished and
classified according to their modes of action. Genetic programming, a
rule-evolving machine learning strategy, allowed respiratory
inhibitors to be discriminated from others by using just two masses.
Metabolic footprinting thus represents a rapid, convenient, and
information-rich method for classifying the modes of action of
antifungal substances.
(Abstract
online)
