Journal Article

The global RNA-binding protein RbpB is a regulator of polysaccharide utilization in Bacteroides thetaiotaomicron

Spiga, Luisella, Faber, Franziska, Langford, Madison, Barquist, Lars, Zhu, Wenhan, Lamm-Schmidt, Vanessa, Rüttiger, Ann-Sophie, Prezza, Gianluca, Westermann, Alexander J., Ryan, Daniel, Reichardt, Sarah

2025

Overview

Paramount to human health, symbiotic bacteria in the gastrointestinal tract rely on the breakdown of complex polysaccharides to thrive in this sugar-deprived environment. Gut Bacteroides are metabolic generalists and deploy dozens of polysaccharide utilization loci (PULs) to forage diverse dietary and host-derived glycans. The expression of the multi-protein PUL complexes is tightly regulated at the transcriptional level. However, how PULs are orchestrated at translational level in response to the fluctuating levels of their cognate substrates is unknown. Here, we identify the RNA-binding protein RbpB and a family of noncoding RNAs as key players in post-transcriptional PUL regulation. We demonstrate that RbpB interacts with numerous cellular transcripts, including a paralogous noncoding RNA family comprised of 14 members, the FopS ( f amily o f p aralogous s RNAs). Through a series of in-vitro and in-vivo assays, we reveal that FopS sRNAs repress the translation of SusC-like glycan transporters when substrates are limited—an effect antagonized by RbpB. Ablation of RbpB in Bacteroides thetaiotaomicron compromises colonization in the mouse gut in a diet-dependent manner. Together, this study adds to our understanding of RNA-coordinated metabolic control as an important factor contributing to the in-vivo fitness of predominant microbiota species in dynamic nutrient landscapes. Gut Bacteroides deploy several polysaccharide utilization loci (PULs) to forage diverse dietary and host-derived glycans. Here, the authors identify the RNA-binding protein RbpB and a family of noncoding RNAs as key players in post-transcriptional PUL regulation, further showing that ablation of RbpB in Bacteroides thetaiotaomicron compromises colonization in the mouse gut in a diet-dependent manner.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 38 / 38/91 / 631/326 / 631/45 / Ablation / Animals / Bacterial Proteins - genetics / Bacterial Proteins - metabolism / Bacteroides / Bacteroides thetaiotaomicron / Bacteroides thetaiotaomicron - genetics / Bacteroides thetaiotaomicron - metabolism / Colonization / Diet / Digestive system / Gastrointestinal system / Gastrointestinal tract / Gene expression / Gene Expression Regulation, Bacterial / Gene regulation / Glycan / Humanities and Social Sciences / Humans / Metabolism / Mice / Mice, Inbred C57BL / multidisciplinary / Non-coding RNA / Nutrient utilization / Players / Polysaccharides / Polysaccharides - metabolism / Post-transcription / Proteins / RNA, Bacterial - genetics / RNA, Bacterial - metabolism / RNA, Small Untranslated - genetics / RNA, Small Untranslated - metabolism / RNA-binding protein / RNA-Binding Proteins - genetics / RNA-Binding Proteins - metabolism / Saccharides / Science / Science (multidisciplinary) / Utilization