Pattern Formation by Motile Bacteria

BERG 9405284在一定条件下，大肠埃希菌和鼠伤寒沙门氏菌趋化菌株的细胞聚集成点状或条状，呈对称排列分布。每个聚集体包含大量细胞，这些细胞响应细胞本身产生的信号而向离散的位置迁移。当细胞悬浮在液体介质中并暴露在环境压力下，或琥珀酸、富马酸或苹果酸(三羧酸循环的中间产物)时，或当细胞生长在以这些化合物之一为底物的软琼脂中时，就会产生这种信号。主要的信号是天冬氨酸，由富马酸和氨产生。第二种信号是谷氨酸，由一种未知的途径产生。我们建议1)建立调节模式形成的一般机制，2)识别谷氨酸途径，3)了解这些途径是如何被不同种类的胁迫激活的，以及4)了解聚集是否具有适应价值。为了达到第一个目标，我们将获得对液体介质中聚集体形成的更定量的描述，表征软琼脂中不同的模式形成，包括迁移段塞，绘制天冬氨酸的梯度图，并试图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聚集在一起，对化学诱导剂做出反应，形成多细胞小体和对称图案。这是一项跨领域的努力，将对压力的感觉转导反应和信号分子的分泌与生物自组织问题联系起来。它是通过一个易于接受遗传和生化操作的模型系统做到这一点的。细菌是最简单的自由生活的有机体。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。这两种类型的细胞都是能动的，可以改变它们的游泳方式，以响应某些化学物质浓度的变化。我们已经找到了细胞分泌化学引诱剂(天冬氨酸和谷氨酸)的条件。结果，细胞相互游动，聚集在一起。当细胞生长在凝胶状的培养基(琼脂)上时，这些聚集体形成各种显著的几何图案，这些图案随可用营养素的量而变化。如果营养浓度足够高，聚集体的行为就像多细胞有机体，在琼脂表面移动并相互消耗。我们能从分子细节上理解这种生物自组织吗？答案是肯定的，因为我们正在处理的是一个由细胞组成的模型系统，这些细胞很容易受到基因生化操作的影响。这项工作连接了当前感兴趣的基础生物学的几个领域，包括运动行为、新陈代谢、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. ***