Department of Molecular Genetics, Groningen Biomolecular Sciences and Biotechnology Institute, and.
Theoretical Biology Group, Centre for Ecological and Evolutionary Studies, University of Groningen, 9747 AG, Groningen, The Netherlands;
Proc Natl Acad Sci U S A. 2014 May 20;111(20):7427-32. doi: 10.1073/pnas.1320063111. Epub 2014 May 5.
When bacteria grow in a medium with two sugars, they first use the preferred sugar and only then start metabolizing the second one. After the first exponential growth phase, a short lag phase of nongrowth is observed, a period called the diauxie lag phase. It is commonly seen as a phase in which the bacteria prepare themselves to use the second sugar. Here we reveal that, in contrast to the established concept of metabolic adaptation in the lag phase, two stable cell types with alternative metabolic strategies emerge and coexist in a culture of the bacterium Lactococcus lactis. Only one of them continues to grow. The fraction of each metabolic phenotype depends on the level of catabolite repression and the metabolic state-dependent induction of stringent response, as well as on epigenetic cues. Furthermore, we show that the production of alternative metabolic phenotypes potentially entails a bet-hedging strategy. This study sheds new light on phenotypic heterogeneity during various lag phases occurring in microbiology and biotechnology and adjusts the generally accepted explanation of enzymatic adaptation proposed by Monod and shared by scientists for more than half a century.
当细菌在含有两种糖的培养基中生长时，它们首先利用首选的糖，只有在这之后才开始代谢第二种糖。在第一个指数生长阶段之后，会观察到一个短暂的非生长滞后阶段，即所谓的双相滞后阶段。通常认为这是细菌为使用第二种糖做准备的阶段。在这里，我们揭示了与滞后阶段代谢适应的既定概念相反，在细菌乳球菌的培养物中会出现两种具有替代代谢策略的稳定细胞类型，并共存。只有其中一种继续生长。每种代谢表型的比例取决于分解代谢物阻遏的水平以及与代谢状态相关的严格反应的诱导，以及表观遗传线索。此外，我们还表明，替代代谢表型的产生可能需要一种风险分散策略。这项研究为微生物学和生物技术中发生的各种滞后阶段的表型异质性提供了新的见解，并调整了由 Monod 提出并被科学家们半个多世纪以来普遍接受的酶适应的解释。
