Morohashi Mineo, Ohashi Yoshiaki, Tani Saeka, Ishii Kotaro, Itaya Mitsuhiro, Nanamiya Hideaki, Kawamura Fujio, Tomita Masaru, Soga Tomoyoshi
Human Metabolome Technologies, Inc., Tsuruoka, Yamagata 997-0052, Japan.
J Biochem. 2007 Aug;142(2):183-91. doi: 10.1093/jb/mvm121. Epub 2007 Jun 1.
The soil bacterium Bacillus subtilis forms dormant, robust spores as a tactic to ensure survival under conditions of starvation. However, the sporulating culture includes sporulating and non-sporulating cells, because a portion of the cell population initiates sporulation in wild-type strain. We anticipated that the population effect must be considered carefully to analyse samples yielding population heterogeneity. We first built a mathematical model and simulated for signal transduction of the sporulation cue to see what mechanisms are responsible for generating the heterogeneity. The simulated results were confirmed experimentally, where heterogeneity is primarily modulated by negative feedback circuits, resulting in generation of a bistable response within the sporulating culture. We also confirmed that mutants relevant to negative feedback yield either sporulating or non-sporulating subpopulations. To see the effect of molecular mechanism between sporulating and non-sporulating cells in distinct manner, metabolome analysis was conducted using the above mutants. The metabolic profiles exhibited distinct characteristics with time regardless of whether sporulation was initiated or not. In addition, several distinct characteristics of metabolites were observed between strains, which was inconsistent with previously reported data. The results imply that careful consideration must be made in the interpretation of data obtained from cells yielding population heterogeneity.
土壤细菌枯草芽孢杆菌形成休眠、健壮的孢子，作为在饥饿条件下确保生存的一种策略。然而，产孢培养物包括产孢细胞和非产孢细胞，因为在野生型菌株中，一部分细胞群体开始产孢。我们预计，在分析产生群体异质性的样本时，必须仔细考虑群体效应。我们首先建立了一个数学模型，并对产孢信号的转导进行了模拟，以了解哪些机制导致了异质性的产生。模拟结果得到了实验证实，其中异质性主要由负反馈回路调节，从而在产孢培养物中产生双稳态反应。我们还证实，与负反馈相关的突变体产生产孢或不产孢的亚群体。为了以不同方式观察产孢细胞和非产孢细胞之间分子机制的作用，我们使用上述突变体进行了代谢组分析。无论是否开始产孢，代谢谱随时间呈现出不同的特征。此外，在菌株之间观察到几种代谢物的明显特征，这与先前报道的数据不一致。结果表明，在解释从产生群体异质性的细胞中获得的数据时，必须谨慎考虑。
