A common bacterial metabolite elicits prion-based bypass of glucose repression
A common bacterial metabolite elicits prion-based bypass of glucose repression
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DOI：
10.7554/elife.17978
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发表时间：
2016-11-29
期刊：
影响因子：
7.7
通讯作者：
Jarosz, Daniel F.
中科院分区：
文献类型：
--
作者：
Garcia, David M.;Dietrich, David;Jarosz, Daniel F.
对发酵葡萄糖代谢的强烈偏好促使了芽殖酵母酿酒酵母的驯化。这个程序可以被一种基于蛋白质的遗传元件（[GAR（+）]朊病毒）绕过，它允许葡萄糖和其他碳源同时代谢。不同的细菌可以诱导酵母细胞获得[GAR（+）]，尽管这种相互作用的分子细节仍然未知。在这里，我们确定了常见的细菌代谢产物乳酸作为一个强大的[GAR（+）]诱导剂。短暂暴露于乳酸导致酵母细胞遗传性地规避葡萄糖抑制。该性状具有[GAR（+）]的决定性遗传特性，并且不需要利用乳酸作为碳源。乳酸也诱导[GAR（+）]样表观遗传状态的真菌，从S。酿酒酵母类似于2亿年前，其中葡萄糖抑制独立进化。据我们所知，这是第一项发现细菌代谢物具有强效诱导朊病毒能力的研究。
Robust preference for fermentative glucose metabolism has motivated domestication of the budding yeast Saccharomyces cerevisiae. This program can be circumvented by a protein-based genetic element, the [GAR(+)] prion, permitting simultaneous metabolism of glucose and other carbon sources. Diverse bacteria can elicit yeast cells to acquire [GAR(+)], although the molecular details of this interaction remain unknown. Here we identify the common bacterial metabolite lactic acid as a strong [GAR(+)] inducer. Transient exposure to lactic acid caused yeast cells to heritably circumvent glucose repression. This trait had the defining genetic properties of [GAR(+)], and did not require utilization of lactic acid as a carbon source. Lactic acid also induced [GAR(+)]-like epigenetic states in fungi that diverged from S. cerevisiae similar to 200 million years ago, and in which glucose repression evolved independently. To our knowledge, this is the first study to uncover a bacterial metabolite with the capacity to potently induce a prion.