The RNA-binding protein RbpB is a central regulator of polysaccharide utilization in gutBacteroides

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. GutBacteroidesare 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. Ablation of RbpB inBacteroides thetaiotaomicrondisplays compromised colonization in the mouse gut in a host diet-dependent manner. Current dogma holds that individual PULs are regulated by dedicated transcriptional regulators. We demonstrate that RbpB acts as a global RNA binder that directly interacts with several hundred cellular transcripts. This includes a paralogous noncoding RNA family comprised of 14 members, the FopS (familyofparalogoussRNAs) cluster. Through a series ofin-vitroandin-vivoassays, we reveal that FopS sRNAs repress the translation of a SusC-like glycan transporter when substrates are limited—an effect antagonized by RbpB. Together, this study implicates RNA-coordinated metabolic control as an important, yet previously overlooked, factor contributing to thein-vivofitness of predominant microbiota species in dynamic nutrient landscapes.

The RNA landscape of the human commensalSegatella coprireveals a small RNA essential for gut colonization

“…Based on homology, S. copri lacks all known small RNA binding proteins. Specifically, it lacks the three main RBPs described Hfq, ProQ, and CsrA in bacteria 46 as well as the recently described new RBP family in B. thetaiotaomicron 47,48 . Of note, genetics of S. copri continue to be challenging, and to date, we lack genetic systems that allow overexpression or ectopic expression of genetic constructs from a neutral genomic site as the pNBU system in Bacteroides spp , which are instrumental for genetic dissection 49–54 .…”