title: Caffeine induces macroautophagy and confers a cytocidal effect on food spoilage yeast in combination with benzoic acid.
abstract: Weak organic acids are an important class of food preservatives that are particularly efficacious towards yeast and fungal spoilage. While acids with small aliphatic chains appear to function by acidification of the cytosol and are required at high concentrations to inhibit growth, more hydrophobic organic acids such as sorbic and benzoic acid have been suggested to function by perturbing membrane dynamics and are growth-inhibitory at much lower concentrations. We previously demonstrated that benzoic acid has selective effects on membrane trafficking in Saccharomyces cerevisiae. Benzoic acid selectively blocks macroautophagy in S. cerevisiae while acetic acid does not, and sorbic acid does so to a lesser extent. Indeed, while both benzoic acid and nitrogen starvation are cytostatic when assayed separately, the combination of these treatments is cytocidal, because macroautophagy is essential for survival during nitrogen starvation. In this report, we demonstrate that Zygosaccharomyces bailii, a food spoilage yeast with relatively high resistance to weak acid stress, also exhibits a cytocidal response to the combination of benzoic acid and nitrogen starvation. In addition, we show that nitrogen starvation can be replaced by caffeine supplementation. Caffeine induces a starvation response that includes the induction of macroautophagy, and the combination of caffeine and benzoic acid is cytocidal, as predicted from the nitrogen starvation data.
authors.affiliation: Department of Biochemistry and Food Science, Hebrew University of Jerusalem, Rehovot, Israel.
authors.forename: Gal
authors.initials: G
authors.lastname: Winter
authors.forename: Reut
authors.initials: R
authors.lastname: Hazan
authors.forename: Alan T
authors.initials: AT
authors.lastname: Bakalinsky
authors.forename: Hagai
authors.initials: H
authors.lastname: Abeliovich
mesh_terms: D001343:Autophagy / Q000502:physiology*; D019817:Benzoic Acid / Q000494:pharmacology*; D002110:Caffeine / Q000494:pharmacology*; D054697:Cytostatic Agents / Q000494:pharmacology*; D004357:Drug Synergism; D005516:Food Microbiology; D005519:Food Preservation; D005656:Fungal Proteins / Q000378:metabolism; D006801:Humans; D009584:Nitrogen / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020068:Zygosaccharomyces / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: D054697:Cytostatic Agents; D005656:Fungal Proteins; D010726:Phosphodiesterase Inhibitors; D002110:Caffeine; D019817:Benzoic Acid; D009584:Nitrogen