Great Lakes Bioenergy Research Center, University of Wisconsin-Madison, Madison, WI 53706, USA; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
Cell Host Microbe. 2022 Feb 9;30(2):200-215.e12. doi: 10.1016/j.chom.2021.12.006. Epub 2022 Jan 6.
Polysaccharide utilization loci (PULs) are co-regulated bacterial genes that sense nutrients and enable glycan digestion. Human gut microbiome members, notably Bacteroides, contain numerous PULs that enable glycan utilization and shape ecological dynamics. To investigate the role of PULs on fitness and inter-species interactions, we develop a CRISPR-based genome editing tool to study 23 PULs in Bacteroides uniformis (BU). BU PULs show distinct glycan-degrading functions and transcriptional coordination that enables the population to adapt upon loss of other PULs. Exploiting a BU mutant barcoding strategy, we demonstrate that in vitro fitness and BU colonization in the murine gut are enhanced by deletion of specific PULs and modulated by glycan availability. PULs mediate glycan-dependent interactions with butyrate producers that depend on the degradation mechanism and glycan utilization ability of the butyrate producer. Thus, PULs determine community dynamics and butyrate production and provide a selective advantage or disadvantage depending on the nutritional landscape.
多糖利用基因座（PULs）是细菌中共调控的基因，可感知营养物质并促进聚糖的消化。人类肠道微生物群成员，尤其是拟杆菌，含有许多能够利用聚糖并塑造生态动态的 PUL。为了研究 PUL 在适应性和种间相互作用中的作用，我们开发了一种基于 CRISPR 的基因组编辑工具来研究 Bacteroides uniformis（BU）中的 23 个 PUL。BU PUL 显示出不同的聚糖降解功能和转录协调，使种群能够在失去其他 PUL 时适应。利用 BU 突变体条形码策略，我们证明在体外适应性和 BU 在小鼠肠道中的定植能力通过删除特定的 PUL 而增强，并受聚糖可用性的调节。PUL 介导与丁酸盐生产者的聚糖依赖性相互作用，这取决于丁酸盐生产者的降解机制和聚糖利用能力。因此，PUL 决定了群落动态和丁酸盐的产生，并根据营养状况提供了选择优势或劣势。
