Pattern Formation by Motile Bacteria

在一定条件下，趋化菌株大肠杆菌和鼠伤寒沙门菌的细胞呈斑点或条纹聚集，呈对称排列分布。每个聚集体包含大量的细胞，这些细胞响应细胞自身产生的信号，向一个离散的位点迁移。当细胞悬浮在液体介质中并暴露在环境压力下，或暴露在琥珀酸盐、富马酸盐或苹果酸盐（三羧酸循环的中间产物）中，或当细胞以这些化合物中的一种作为底物生长在软琼脂中时，就会产生这种信号。主要信号是由富马酸和氨产生的天冬氨酸。第二种信号是谷氨酸，由一种未知的途径产生。我们建议1)建立模式形成的一般调节机制，2)识别谷氨酸通路，3)了解这些通路如何被不同类型的应激激活，4)了解聚集是否具有适应价值。为了实现第一个目标，我们将对液体介质中聚集体的形成进行更定量的描述，表征软琼脂中不同的模式形成，包括迁移鼻涕虫，绘制天冬氨酸的梯度，并尝试构建合适的数学模型。更广泛地说，我们希望了解大量相同的细胞如何能够在化学引诱剂的作用下聚集在一起，形成多细胞体和对称模式。这是一个跨领域的努力，将应激和信号分子分泌的感觉转导反应与生物自组织问题联系起来。它是通过一个易于遗传和生化操作的模型系统来实现的。细菌是最简单的自由生物。众所周知的物种包括生活在肠道中的大肠杆菌和导致食物中毒的鼠伤寒沙门氏菌。这两种细胞都是可运动的，可以根据某些化学物质浓度的变化改变游动的方式。我们已经发现了细胞分泌化学引诱剂（氨基酸天冬氨酸和谷氨酸）的条件。结果，细胞彼此游动并聚集在一起。当细胞在凝胶状培养基（琼脂）上生长时，这些聚集体形成各种显著的几何图案，这些图案根据可用营养物质的量而变化。如果营养物质浓度足够高，聚集体的行为就像多细胞生物一样，在琼脂表面移动并相互消耗。我们能从分子的细节上理解这种生物自组织吗？答案是肯定的，因为我们正在处理一个由细胞组成的模型系统，它很容易接受遗传生化操作。这项工作将当前感兴趣的基础生物学的几个领域联系起来，包括运动行为，代谢，对压力的反应，自组织和模式形成。＊＊＊

Berg 9405284 Under certain conditions, cells of chemotactic strains of the bacteria Escherichia coli and Salmonella typhimurium aggregate in spots or stripes distributed in symmetrical arrays. Each aggregate contains a large number of cells that have migrated toward a discrete locus in response to a signal generated by the cells themselves. This signal is produced when cells are suspended in liquid media and exposed to environmental stress, or to succinate, fumarate or malate (intermediates of the tricarboxylic-acid cycle), or when cells are grown in soft agar with one the these compounds as substrate. The primary signal is aspartate, produced from fumarate and ammonia. A secondary signal is glutamate, produced by an unidentified pathway. We propose 1) to establish the general mechanisms regulating pattern formation, 2) to identify the glutamate pathway, 3) to learn how these pathways are activated by different kinds of stress, and 4) to learn whether aggregation has an adaptive value. To meet the first goal, we will obtain a more quantitative description of aggregate formation in liquid media, characterize different modes of pattern formation in soft agar, including migrating slugs, map gradients of aspartate, and attempt to construct suitable mathematical models. More broadly, we hope to learn how large numbers of identical cells are able to come together in response to chemoattractants to form multicellular bodies and symmetrical patterns. This is a cross-field endeavor that links sensory transduction responses to stress and secretion of signal molecules to the problem of biological self-organization. It does so with a model system readily amenable to genetic and biochemical manipulation. %%% Bacteria are the simplest free-living organisms. Species that are well understood include Escherichia coli, that lives in your gut, and Salmonella typhimurium, that causes food poisoning. Both cell types are motile and can change the way they swim in response t o changes in concentration of certain chemicals. We have found conditions under which the cells excrete chemical attractants (the amino acids aspartate and glutamate). As a result, the cells swim toward one another and aggregate. When cells are grown on a gel- like medium (agar), these aggregates form a variety of remarkable geometric patterns, which change depending upon the amount of available nutrient. If the nutrient concentration is high enough, the aggregates behave like multicellular organisms, moving over the surface of the agar and consuming one another. Can we understand this biological self-organization in molecular detail? The answer is yes, because we a dealing with a model system made of cells readily amenable to genetic biochemical manipulation. This work links several areas of basic biology of current interests, including motile behavior, metabolism, response to stress, self- organization and pattern formation. ***