A Master Regulator of Bacteroides thetaiotaomicron Gut Colonization Controls Carbohydrate Utilization and an Alternative Protein Synthesis Factor

Microbial colonization of the mammalian gut is largely ascribed to the ability to utilize nutrients available in that environment. To understand how beneficial microbes establish a relationship with their hosts, it is crucial to determine what other abilities promote gut colonization. We now report that colonization of the murine gut by the beneficial microbe requires activation of a putative translation factor by the major transcriptional regulator of gut colonization and carbohydrate utilization. To ascertain how this regulator-called BT4338-promotes gut colonization, we identified BT4338-regulated genes and BT4338-bound DNA sequences. Unexpectedly, the gene whose expression was most reduced upon inactivation was , specifying a putative translation factor. We determined that activation by BT4338 is conserved in another species and essential for gut colonization in because a mutant lacking the BT4338 binding site in the promoter exhibited a colonization defect similar to that of a mutant lacking the gene. Furthermore, we demonstrated that BT4338 promotes gut colonization independently of its role in carbohydrate utilization because the gene was dispensable for utilization of carbohydrates that depend on Our findings suggest that microbial gut colonization requires the use of alternative protein synthesis factors. The bacteria occupying the mammalian gut have evolved unique strategies to thrive in their environment. organisms, which often comprise 25 to 50% of the human gut microbiota, derive nutrients from structurally diverse complex polysaccharides, commonly called dietary fibers. This ability requires an expansive genetic repertoire that is coordinately regulated to achieve expression of those genes dedicated to utilizing only those dietary fibers present in the environment. Here we identify the global regulon of a transcriptional regulator necessary for dietary fiber utilization and gut colonization. We demonstrate that this transcription factor regulates hundreds of genes putatively involved in dietary fiber utilization as well as a putative translation factor dispensable for growth on such nutrients but necessary for survival in the gut. These findings suggest that gut bacteria coordinate cellular metabolism with protein synthesis via specialized translation factors to promote survival in the mammalian gut.