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

Ann-Sophie Rüttiger, Daniel Ryan, Luisella Spiga, Vanessa Lamm-Schmidt, Gianluca Prezza, Sarah Reichardt, Madison Langford, Lars Barquist, Franziska Faber, Wenhan Zhu and Alexander J. Westermann ()
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Ann-Sophie Rüttiger: University of Würzburg
Daniel Ryan: University of Würzburg
Luisella Spiga: Vanderbilt University
Vanessa Lamm-Schmidt: Helmholtz Centre for Infection Research (HZI)
Gianluca Prezza: Helmholtz Centre for Infection Research (HZI)
Sarah Reichardt: Helmholtz Centre for Infection Research (HZI)
Madison Langford: Vanderbilt University
Lars Barquist: Helmholtz Centre for Infection Research (HZI)
Franziska Faber: Helmholtz Centre for Infection Research (HZI)
Wenhan Zhu: Vanderbilt University
Alexander J. Westermann: University of Würzburg

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: Abstract 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 (family of paralogous sRNAs). 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.

Date: 2025
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DOI: 10.1038/s41467-024-55383-8

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