Genome-wide Response of Saccharomyces cerevisiae to the Neurotoxic Fungal Volatile Organic Compound 1-octen-3-ol

Microbial volatile organic compounds (VOCs) are produced in mixtures of alcohols, aldehydes, acids, ketones, terpenes, etc., and are emitted at varying concentrations depending on the species, substrate, incubation period and other environmental parameters. Microbial VOCs serve as chemical signals influencing growth, germination, and pathogenicity. Previously, 1-octen-3-ol was found to be toxic to cell cultures, flies and humans, although the precise mechanism of toxicity has remained unknown. In this study, Saccharomyces cerevisiae (yeast) was used as an experimental model and the toxicity of 1-octen-3-ol was determined using a serial dilution spot assay. Growth inhibition occurred upon exposure to 40 ppm 1-octen-3-ol, while at 120 ppm, yeast growth was completely inhibited during the 48-hr assay. Subsequently, to determine the mode of action of this compound, a genome-wide screen of the yeast deletion library was conducted to identify the genes or genetic pathways involved in resistance. We identified 91 mutants that were resistant, and functional analysis revealed that genes disrupted in vacuolar/vesicular transport or endosomal transport were highly prevalent in providing resistance to 1-octen-3-ol. Specifically, when either the retrograde or degradative sorting pathways are disrupted, yeast cells are resistant to 1-octen-3-ol. These results suggest that protein or membrane turnover may be involved in providing resistance to 1-octen-3-ol, since the identified complexes are involved in both processes. This study is the first genome-wide screen of a deletion library using gas-phase exposure to a biogenic volatile organic compound, and provides the first insight into the cellular mechanisms by which fungal VOCs impact eukaryotic cells.