Fig. 8: Model for the DcuSR-mediated L-malate signaling regulatory pathway in EHEC O157:H7. | Nature Communications

Fig. 8: Model for the DcuSR-mediated L-malate signaling regulatory pathway in EHEC O157:H7.

From: Enterohaemorrhagic E. coli utilizes host- and microbiota-derived L-malate as a signaling molecule for intestinal colonization

Fig. 8: Model for the DcuSR-mediated L-malate signaling regulatory pathway in EHEC O157:H7.The alt text for this image may have been generated using AI.

When EHEC O157:H7 enters the human large intestine, where L-malate levels are high, the TCS sensor kinase DcuS responds to the high L-malate signal and undergoes autophosphorylation, after which the phosphoryl group is transferred between DcuS and its cognate DNA-binding transcriptional regulator DcuR. On the one hand, phosphorylated DcuR (DcuR-P) directly activates the expression of genes involved in anaerobic L-malate transport and metabolism, including dcuB, fumB and frdABCD, which encode anaerobic L-malate transporters, fumarase FumB, and fumarate reductase. These highly expressed genes ensure that EHEC O157:H7 efficiently imports L-malate and subsequently converts it into fumarate to fuel anaerobic fumarate respiration, thereby promoting bacterial growth and colonization in the large intestine. On the other hand, DcuR-P directly activates the expression of ler (encoding the master regulator of LEE genes) by binding the ler promoter, after which Ler activates other LEE genes to promote EHEC O157:H7 T3SS-dependent adherence to the epithelial cells of the large intestine. MK menaquinone, MKH2 menaquinol, LEE locus of enterocyte effacement, T3SS type III secretion system.

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