Intercellular signaling in Myxococcus xanthus

黄色粘球菌细胞在营养生长和多细胞子实体形成过程中，在固体表面表现出协调的细胞运动。这些复杂的社会行为使该细菌成为研究细胞间信号和微生物发育的极佳模型系统。我们的研究重点是了解社会滑动运动(S运动)的力学和生理基础，以及子实体形成过程中运动的化学趋化控制。在上一次资助期间，我们发现了两种细胞表面附属物的一些重要的分子功能，这两种附属物是社会运动所必需的：IV型菌毛和纤维。基于这些发现，我们推测黄色微囊藻的定向运动涉及FRZ化学感觉系统对菌毛开关频率的控制。我们还推测，原丝是一种自身产生的细胞外基质材料，是黄曲霉的主要化学诱导剂，并为黄曲霉子实体的形成提供了重要的信号。我们提出以下具体目标来验证这些假说：1.获得毛依赖运动的直接物理证据，并研究其与FRZ化学感觉系统的相互作用；2.获得子实体形成过程中纤维引导的趋化运动的直接视觉证据；3.鉴定参与纤维梯度自身产生的分子成分。这些研究将有助于我们理解群居、群猎、细胞间信号传递和子实体形成的分子机制。它还将提供对滑动运动和细菌运动/趋化系统进化的分子理解。由于黄曲霉的S运动和聚集与假单胞菌和奈瑟氏菌等病原菌的抽动运动和生物膜形成非常相似，因此这些研究也可能为进一步研究这些事件的分子特征提供线索，从而导致针对这些病原菌的新的治疗方法。

Myxococcus xanthus cells exhibit coordinated cell movements on a solid surface during vegetative growth and multicellular fruiting body formation. These complex social behaviors make this bacterium an excellent model system for studying intercellular signaling and microbial development. The focus of our research is to understand the mechanical and physiological basis of social gliding motility (S-motility) and the chemotactic control of motility during fruiting body formation. During the last grant period, we discovered some important molecular functions of two cell surface appendages that are required for social motility: the type IV pili and fibrils. Based on these findings, we hypothesize that directed motility in M.xanthus involves the control of pilus switching frequency by the frz chemosensory system. We also hypothesize that fibril, a self-generated extracellular matrix material, is a major chemoattractant for M. xanthus and provides an important signal for fruiting body formation in M. xanthus. We propose the following specific aims to test these hypotheses: 1. to obtain direct physical evidence of pilus dependent motility and study its interaction with the frz chemosensory system; 2. to obtain direct visual evidence of fibril-guided chemotactic movement during fruiting body formation; 3. to identify molecular components involved in self-generation of fibril gradient. The studies will help us to understand the molecular mechanisms of social swarming, social hunting, intercellular signaling, and fruiting body formation. It will also provide a molecular understanding of gliding motility and the evolution of bacterial motility/chemotaxis systems. Since the S-motility and aggregation of M. xanthus are very similar to twitching motility and biofilm formation in pathogenic bacteria like Pseudomonas and Neisseria, the studies may also provide clues for further molecular characterization of these events, leading to new treatments against these pathogenic bacteria.