Auxotrophic strains starving for their cognate nutrient, termed auxotrophic starvation, are characterized by a shorter lifespan, higher glucose wasting phenotype, and inability to accomplish cell cycle arrest when compared to a “natural starvation,” where a cell is starving for natural environmental growth-limiting nutrients such as phosphate. Since evidence of this physiological response is limited to only a subset of auxotrophs, we evaluated a panel of auxotrophic mutants to determine whether these responses are characteristic of a broader range of amino acid auxotrophs. Based on the starvation survival kinetics, the panel of strains was grouped into three categories—short-lived strains, strains with survival similar to a prototrophic wild type strain, and long-lived strains. Among the short-lived strains, we observed that the tyrosine, asparagine, threonine, and aspartic acid auxotrophs rapidly decline in viability, with all strains unable to arrest cell cycle progression. The three basic amino acid auxotrophs had a survival similar to a prototrophic strain starving in minimal media. The leucine, tryptophan, methionine, and cysteine auxotrophs displayed the longest lifespan. We also demonstrate how the phenomenon of glucose wasting is limited to only a subset of the tested auxotrophs, namely the asparagine, leucine, and lysine auxotrophs. Furthermore, we observed pleiotropic phenotypes associated with a subgroup of auxotrophs, highlighting the importance of considering unintended phenotypic effects when using auxotrophic strains especially in chronological aging experiments.

中文翻译：

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在营养缺陷型饥饿条件下表征一组氨基酸营养缺陷型细胞

营养缺陷型菌株缺乏同源营养物质，称为营养缺陷型饥饿，与“自然饥饿”（细胞渴望自然环境生长）相比，其特征是寿命较短、葡萄糖消耗表型较高，并且无法完成细胞周期停滞。限制磷酸盐等营养素。由于这种生理反应的证据仅限于营养缺陷型的一个子集，因此我们评估了一组营养缺陷型突变体，以确定这些反应是否是更广泛的氨基酸营养缺陷型的特征。根据饥饿生存动力学，这组菌株被分为三类：短命菌株、与原养型野生型菌株相似的存活菌株和长寿命菌株。在短命菌株中，我们观察到酪氨酸、天冬酰胺、苏氨酸和天冬氨酸营养缺陷型菌株的活力迅速下降，所有菌株都无法阻止细胞周期进程。三种碱性氨基酸营养缺陷型菌株的存活率与在基本培养基中挨饿的原养型菌株相似。亮氨酸、色氨酸、蛋氨酸和半胱氨酸营养缺陷型细胞的寿命最长。我们还证明了葡萄糖消耗现象如何仅限于所测试的营养缺陷型细胞的一个子集，即天冬酰胺、亮氨酸和赖氨酸营养缺陷型细胞。此外，我们观察到与营养缺陷型亚群相关的多效性表型，强调了在使用营养缺陷型菌株时考虑意外表型效应的重要性，特别是在按时间顺序老化的实验中。