Decoding contact-dependent communication and coordination in bacteria

长期以来，细菌是“一袋酶”的概念在过去几年里发生了范式的转变，许多真核特征现在也在细菌中被发现。其中一个特征是多细胞(通过分化的细胞命运)，如革兰氏阴性社会细菌黄色粘菌；饥饿时，群体诱导某些细胞形成充满孢子的子实体，其他细胞探索当地环境，还有第三个亚群编程细胞死亡，为同类进食提供营养，所有这些都没有传统的群体群体感应系统。个别黄花莲细胞在坚硬的表面上移动，会留下粘液多糖的痕迹，随后可能会有细胞和蜂群跟随。粘液尾迹还含有先前转移的细胞留下的外膜小泡/管。然而，细胞表面因素在区分“自我”和“非我”来源中的作用也从未被描述过。因此，细菌如何仅仅通过与自身产生的信号接触并相互作用来影响多细胞行为，从而在整个种群中进行沟通和协调行动，仍然存在许多问题。 这项研究计划旨在确定细菌表面动力学在细菌种群行为协调中的机制和作用。具体地说，我们将研究后续的“Chase”细胞优先遵循先前从“种子”细胞沉积的粘液痕迹的基础，以及在这些痕迹中从亲缘细胞摄取外膜碎片是否影响这一结果。作为补充，我们将阐明粘液的产生过程以及有助于其粘附性的多糖的化学性质。由于外膜碎片普遍存在于泥迹中，我们还将描述导致表面材料动态沉积的事件，包括膜本身的结构因素，这些因素可能使其容易出现这种现象。最后，我们将确定负责区分亲缘细胞和非亲缘细胞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。这项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，这些细菌成分对接触中介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土壤和河流、胃肠道及其相关微生物群等各种生态环境中的生存和持久性的理解。

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.