Fig. 6: Schematic model of FruR-dependent regulation of the fru operon in F. prausnitzii.

Prior to fructose exposure in the host intestine, FruR hinders RNAP interaction with the fru promoter by binding to motifs that cover the −35 and −10 elements. When fructose is available, it is transported into bacterial cells as fructose-1-phosphate (F1P) via the PTS phosphorelay system involving EI, HPr1, HPr2 and fructose-specific EII, with HPr2 undergoing serine phosphorylation. FruR then forms a complex with F1P, leading to its dissociation from the −35 and −10 elements as well as TSS downstream region, thereby freeing the RNAP binding site. Serine-phosphorylated HPr2 subsequently binds to the F1P-FruR complex, resulting in the formation of the F1P-HPr2(Ser-P)-FruR complex. This complex then facilitates RNAP binding to the −35 and −10 elements of the fru promoter, initiating transcription.