A WYL domain transcription factor regulates Lactiplantibacillus plantarum intestinal colonization via perceiving c-di-GMP

Cyclic diguanosine monophosphate (c-di-GMP) functions as a crucial bacterial second messenger to control diverse biological functions. Although numerous studies have reported the health effects of Lactiplantibacillus plantarum, the regulatory role of c-di-GMP in L. plantarum remains elusive. Here we show that c-di-GMP functions as an important signal molecule for intestinal colonization of L. plantarum. The intracellular c-di-GMP pool in this probiotic is governed principally by the diguanylate cyclases DgcB, DgcC, and DgcD and the phosphodiesterases PdeA and PdeD. Moreover, we reveal that the WYL domain transcription factor MbpR is a c-di-GMP effector in L. plantarum WCFS1. MbpR reduces the transcription level of mucin-binding proteins (MucBPs) via binding to a special motif within the coding sequences. Perception of c-di-GMP by the WYL domain reversed the inhibitory effect of MbpR on the expression of MucBPs, resulting in increased adherence to intestinal epithelial cells by L. plantarum. Overall, our study provides evidence that a WYL domain transcription factor participates in probiotic colonization by sensing c-di-GMP.