Thiamine pyrophosphate riboswitches in Bacteroides species regulate transcription or translation of thiamine transport and biosynthesis genes

Abstract

Thiamine (vitamin B1) and its phosphorylated precursors are necessary for decarboxylation reactions required in carbohydrate and branched chain amino acid metabolism. Due to its critical roles in central metabolism, thiamine is essential for human and animal hosts and their resident gut microbes. However, little is known about how thiamine availability shapes the composition of gut microbial communities and the physiology of individual species within those communities. Our previous work has implicated both thiamine biosynthesis and transport activities in the fitness of Bacteroides species. To better understand thiamine-dependent gene regulation in Bacteroides, we examined thiamine biosynthesis and transport genes in three representative species: Bacteroides thetaiotaomicron, Bacteroides uniformis, and Bacteroides vulgatus. All three species possess thiamine biosynthetic operons controlled by highly conserved cis-acting thiamine pyrophosphate (TPP) riboswitches. B. thetaiotaomicron and B. uniformis have additional TPP riboswitch-controlled operons encoding thiamine transport functions. Transcriptome analyses showed that each Bacteroides species had a distinct transcriptional response to exogenous thiamine. Analysis of transcript levels and translational fusions demonstrated that in B. thetaiotaomicron, the TPP riboswitch upstream of biosynthesis genes acts at the level of transcription, while TPP riboswitches upstream of transport operons work at the level of translation. In B. uniformis and B. vulgatus, TPP riboswitches work at the transcriptional level to control downstream operons. The varying responses to exogenous thiamine and use of varied regulatory mechanisms may play an important role in niche establishment by the Bacteroidetes in the complex and constantly shifting gut environment. ImportanceBacteroides species are important and abundant members of human gut microbiome communities. Their activities in the gut are influenced by constant changes in nutrient availability. In this study, we investigated the genetic basis of thiamine (Vitamin B1) uptake and biosynthesis in three representative Bacteroides species. We found species-specific differences in the response to exogenous thiamine, and distinct mechanisms for regulation of uptake and biosynthesis gene expression. Our work implies that gut Bacteroides have evolved distinct strategies for making or acquiring an essential nutrient. These mechanisms may play an important role in the success of Bacteroides in establishing a niche within complex gut microbiome communities.