title: Alcohols inhibit translation to regulate morphogenesis in C. albicans.
abstract: Many molecules are secreted into the growth media by microorganisms to modulate the metabolic and physiological processes of the organism. For instance, alcohols like butanol, ethanol and isoamyl alcohol are produced by the human pathogenic fungus, Candida albicans and induce morphological differentiation. Here we show that these same alcohols cause a rapid inhibition of protein synthesis. More specifically, the alcohols target translation initiation, a complex stage of the gene expression process. Using molecular techniques, we have identified the likely translational target of these alcohols in C. albicans as the eukaryotic translation initiation factor 2B (eIF2B). eIF2B is the guanine nucleotide exchange factor for eIF2, which supports the exchange reaction where eIF2.GDP is converted to eIF2.GTP. Even minimal regulation at this step will lead to alterations in the levels of specific proteins that may allow the exigencies of the fungus to be realised. Indeed, similar to the effects of alcohols, a minimal inhibition of protein synthesis with cycloheximide also causes an induction of filamentous growth. These results suggest a molecular basis for the effect of various alcohols on morphological differentiation in C. albicans.
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, United Kingdom.
authors.forename: Nkechi E
authors.initials: NE
authors.lastname: Egbe
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, United Kingdom.
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Paget
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, United Kingdom.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, United Kingdom. Electronic address: mark.p.ashe@manchester.ac.uk.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Ashe
mesh_terms: D020001:1-Butanol / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development / Q000472:pathogenicity; D000431:Ethanol / Q000494:pharmacology*; D005656:Fungal Proteins / Q000378:metabolism; D025301:Hyphae / Q000187:drug effects; D009024:Morphogenesis / Q000187:drug effects*; D009154:Mutation; D000439:Pentanols / Q000494:pharmacology*; D010766:Phosphorylation; D014176:Protein Biosynthesis / Q000187:drug effects*; D012441:Saccharomyces cerevisiae / Q000187:drug effects
chemical_list: D005656:Fungal Proteins; D000439:Pentanols; D000431:Ethanol; D020001:1-Butanol; C029683:isopentyl alcohol
keywords: Candida albicans; Eukaryotic initiation factor 2B (eIF2B); Filamentous growth; Protein synthesis
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