Polysaccharide utilization loci in Bacteroides determine population fitness and community-level interactions

• Published in: Cell host & microbe 2022-02, Vol.30 (2), p.200-215.e12
• Main Authors: Feng, Jun, Qian, Yili, Zhou, Zhichao, Ertmer, Sarah, Vivas, Eugenio I., Lan, Freeman, Hamilton, Joshua J., Rey, Federico E., Anantharaman, Karthik, Venturelli, Ophelia S.
• Format: Article
• Language: English
• Subjects: Animals; Bacterial Proteins - metabolism; Bacteroides; Bacteroides - genetics; Bacteroides - metabolism; BASIC BIOLOGICAL SCIENCES; butyrate production; CRISPR-based genome editing; Gastrointestinal Microbiome - genetics; Genes, Bacterial; Genetic Fitness; Humans; Mice; microbial interactions; microbial metabolism; microbiome engineering; polysaccharide utilization loci; Polysaccharides - metabolism; synthetic human gut communities; transcriptional regulation
• ISSN: 1931-3128; 1934-6069
• DOI: 10.1016/j.chom.2021.12.006

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. [Display omitted] •CRISPR genome-editing tool examines the impact of 23 PULs in B. uniformis•PULs in B. uniformis display transcriptional coordination•B. uniformis PULs provide a nutrient-dependent fitness advantage or disadvantage•B. uniformis PULs determine community dynamics and butyrate production Polysaccharide utilization loci (PULs) in the human gut microbiome determine microbial fitness and community-level functions. Feng et al. show that PULs in Bacteroides uniformis provide a fitness advantage or disadvantage that depends on nutrient availability. B. uniformis PULs display transcriptional coordination and play key roles in shaping butyrate production.