Transcriptome kinetics of Saccharomyces cerevisiae strain BY4742 in response to viral killer toxin K1

The A/B toxin K1 secreted by virus-infected Saccharomyces cerevisiae strains kills sensitive cells via disturbance of cytoplasmic membrane function. Despite decades of research, the mechanisms underlying K1 toxicity and immunity have not been elucidated yet. In a novel approach, this study aimed to characterize transcriptional changes of K1-treated sensitive yeast cells in a time-dependent manner. Global transcriptional profiling revealed substantial cellular adaptations in target cells resulting in 1189 differentially expressed genes in total. Killer toxin K1 induced oxidative, cell wall and hyperosmotic stress responses as well as rapid down-regulation of transcription and translation. Essential pathways regulating energy metabolism were also significantly affected by the toxin. Remarkably, a futile cycle of the osmolytes trehalose and glycogen was identified probably representing a critical feature of K1 intoxication. In silico analysis suggested several transcription factors involved in K1-triggered signal transduction. The identified transcriptional changes implicate an evolutionary conserved response at least initially counteracting ionophoric toxin action, and provide valuable hints to elucidate the still unknown molecular events leading to K1 toxicity and immunity.

病毒感染的酿酒酵母（Saccharomyces cerevisiae）菌株分泌的AB类毒素K1（A/B toxin K1）可通过干扰细胞质膜功能杀灭敏感酵母细胞。尽管已有数十年研究积累，K1毒素的毒性与免疫机制仍未被阐明。本研究采用创新研究策略，以时间依赖性方式解析经K1毒素处理的敏感酵母细胞的转录组变化特征。全转录组分析显示，靶细胞发生显著的细胞适应性改变，共计鉴定出1189个差异表达基因（differentially expressed genes）。杀伤毒素K1可诱导氧化应激、细胞壁应激与高渗应激应答，并快速下调转录与翻译过程。调控能量代谢的核心通路亦受到该毒素的显著影响。值得注意的是，本研究鉴定出渗透调节物质海藻糖（trehalose）与糖原（glycogen）的无效循环，这可能是K1毒素中毒的关键特征。计算机模拟（in silico）分析提示，多种转录因子（transcription factors）参与K1毒素触发的信号转导（signal transduction）过程。本研究鉴定的转录组变化表明，该应答至少在初始阶段是一种进化保守的、可拮抗离子载体类毒素（ionophoric toxin）作用的防御机制，同时为阐明目前仍未明确的K1毒性与免疫相关分子事件提供了重要研究线索。