ChIP-seq profiles of RwpL-bound regions on the L. plantarum WCFS1 chromosome.

c-di-AMP is a crucial secondary messenger to regulate bacterial physiology in response to environmental changes. However, its role in Lactiplantibacillus plantarum remains to be uncovered. Here, we demonstrated that RwpL is a c-di-AMP receptor mediating the adhesion of L. plantarum to intestinal epithelial cells. We further showed that c-di-AMP counteracts RwpL-mediated suppression of WxlA, a protein that binds to human fibronectin on epithelial surfaces. Our results support the central role of c-di-AMP in regulating the probiotic activity of L. plantarum.