Regulatory role of pyruvate-sensing BtsSR in biofilm formation by Escherichia coli K-12

Pyruvate, the key regulator in connection of a variety of metabolic pathways, influences transcription of the Escherichia coli genome through controlling the activity of two pyruvate-sensing two-component systems (TCSs), BtsSR and PyrSR. Previously, we identified the whole set of regulatory targets of PyrSR with low-affinity to pyruvate. Using gSELEX screening system, we found here that BtsSR with high-affinity to pyruvate regulates more than 100 genes including as many as 13 transcription factors genes including the csgD gene encoding the master regulator of biofilm formation. CsgD regulates more than 20 target genes including the csg operons encoding the Curli fimbriae. In addition, we identified the csgBAC as one of the regulatory targets of BtsR, thus indicating the involvement of two pyruvate-dependent regulatory pathways of the curli formation: indirect regulation by CsgD; and direct regulation by BtsR. Based on the findings of the whole set of regulatory targets by two pyruvate-sensing BtsR and PyrR, we further propose an innovative concept that the pyruvate level-dependent regulation of different gene sets takes place through two pyruvate-sensing TCS systems, high-affinity BtsSR and low-affinity PyrSR to pyruvate.