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PMID: 15466562 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Discrimination of modes of action of antifungal substances by use of metabolic footprinting.

Applied and environmental microbiology ·Vol. 70 ·No. 10 ·2004-10-00 ·Pages 6157-65

Allen J, Davey HM, Broadhurst D, Rowland JJ, Oliver SG, Kell DB

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.

MeSH Terms
Antifungal Agents/classification,pharmacology Antimetabolites/pharmacology Artificial Intelligence Discriminant Analysis Mass Spectrometry Models, Biological Saccharomyces cerevisiae/drug effects,growth & development,metabolism
Chemicals
Antifungal Agents Antimetabolites
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Allen Jess
Department of Biological Sciences, University of Wales, Aberystwyth, UK.
Davey Hazel M
Broadhurst David
Rowland Jem J
Oliver Stephen G
Kell Douglas B
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Article Info
Journal
Applied and environmental microbiology
Abbr.
Appl Environ Microbiol
ISSN
0099-2240
DOI
10.1128/AEM.70.10.6157-6165.2004
Published
2004-10-00
Pages
6157-65
Language
English
Region
United States
NLM ID
7605801
PMCID
PMC522091
Subset
IM
Grants
Biotechnology and Biological Sciences Research Council · E19354 · United Kingdom
Biotechnology and Biological Sciences Research Council · E19355 · United Kingdom
External Links
PubMed source DOI: 10.1128/AEM.70.10.6157-6165.2004 PMC Full Text View journal details
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