Decoding contact-dependent communication and coordination in bacteria

长期以来，细菌是“酶袋”的观念在过去几年中发生了范式转变，现在在细菌中也发现了许多真核生物特征。其中一个特征是多细胞性（通过分化的细胞命运），如革兰氏阴性社会性细菌黄粘球菌；饥饿时，群体诱导某些细胞形成充满孢子的子实体，另一些细胞探索当地环境，第三个亚群体的细胞程序化死亡，为同类相食提供营养，所有这些都没有传统的群体感应系统。在坚硬的表面上移动的单个黄色分枝杆菌细胞会留下粘液多糖的痕迹，随后的细胞和群体可以跟随这些痕迹。黏液痕迹还包含先前转运细胞留下的外膜囊泡/管。然而，细胞表面因子在“自我”与“非自我”来源的物质区分中的作用也从未被描述过。因此，细菌如何在整个种群中通过自我产生的信号和彼此之间的接触来影响多细胞行为来沟通和协调它们的行动，仍然存在许多问题。***本研究项目旨在确定细菌表面动力学在细菌群体行为协调中的机制和作用。具体来说，我们将研究随后的“追逐”细胞优先跟随先前从“种子”细胞沉积的黏液轨迹的基础，以及这些轨迹中从亲属细胞摄取外膜碎片是否会影响这一结果。此外，我们将阐明粘液产生的过程以及促成其粘连性的多糖的化学性质。由于外膜碎屑在泥道中普遍存在，我们还将描述导致这种表面物质动态沉积的事件，包括膜本身的结构因素，可能使其倾向于这种现象。最后，我们将确定负责区分kin细胞与那些不相关的表面相关细菌因子。我们将通过使用多学科和尖端的微流体、点击化学、结构生物学和高通量筛选技术来解决这些问题，从而对细菌外膜动力学的机制和作用产生前所未有的见解。该研究计划的长期愿景是全面了解细菌成分之间的相互作用，这些成分对接触介导的沟通和基本行为协调至关重要；这将彻底改变我们对细菌在生态位中的生存和持久性的理解，从土壤和河流到胃肠道及其相关微生物群

The long-held notion of bacteria as “bags of enzymes” has undergone a paradigm shift in the past several years, with many eukaryotic traits now also identified in bacteria. One such trait is multicellularity (through differentiated cell fates), as exemplified by the Gram-negative social bacterium Myxococcus xanthus; upon starvation, swarms induce formation of spore-filled fruiting bodies by certain cells, exploration of the local environment by others, and programmed cell death by yet a third subpopulation to provide nutrients for cannibalistic feeding, all without conventional quorum sensing systems. Individual M. xanthus cells moving on hard surfaces leave behind slime polysaccharide trails, which can be followed by subsequent cells and swarms. Slime trails also contain outer-membrane vesicles/tubes left behind by previously-transited cells. However, the role of cell-surface factors in the discrimination of material from “self” vs. “non-self” sources has also never been characterized. As such, numerous questions remain as to how bacteria can communicate and coordinate their actions across an entire population simply through contact with self-generated signals and each other to effect multicellular behaviour.***This research program aims to determine the mechanisms and roles of bacterial surface dynamics in the coordination of bacterial population behaviour. Specifically, we will examine the basis by which subsequent “chase” cells preferentially follow previously-deposited slime trails from “seed” cells, and whether or not the uptake of outer-membrane debris from kin cells in these trails affects this outcome. Complementarily, we will elucidate the process by which slime is produced as well as the chemical properties of the polysaccharide that contribute to its adhesiveness. As outer-membrane debris is prevalent in slime trails, we will also characterize the events responsible for this dynamic deposition of surface material, including the structural factors of the membrane itself that may predispose it to such phenomena. Finally, we will identify the surface-associated bacterial factors responsible for distinguishing kin cells from those that are not related. We will address these questions through the use of multidisciplinary and cutting-edge microfluidics, click chemistry, structural biology, and high-throughput screening techniques, yielding unprecedented insights into the mechanisms and roles of outer-membrane dynamics in bacteria. The long-term vision for this research program is to develop a comprehensive understanding of the interplay between bacterial components that are crucial for contact-mediated communication and fundamental behavioral coordination; this will revolutionize our understanding of bacterial survival and persistence in niches as diverse as soils and rivers, to the gastrointestinal tract and its associated microbiota.**