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A c-di-AMP receptor mediates epithelial adhesion of Lactiplantibacillus plantarum

ABSTRACT: Cyclic di-adenosine monophosphate (c-di-AMP) is a crucial second messenger used by bacteria to mediate bacterial-host interactions. However, its roles in Lactiplantibacillus plantarum remain poorly understood. Here, we identify RwpL, which consists solely of an HTH domain, as a c-di-AMP receptor in L. plantarum WCFS1. RwpL mediates epithelial adhesion of L. plantarum WCFS1 and functions as both a transcription inhibitor and activator, with transcriptional output determined by the position of its binding site relative to the transcription start site (TSS) of target genes. Specifically, RwpL inhibits wxlA transcription by binding downstream of its TSS, thus reducing WxlA interactions with fibronectin, a matrix protein on the surface of intestinal epithelia. In contrast, RwpL activates transcription of the matrix-degrading metalloprotease gene mmpL by recruiting the sigma factor RpoA upstream of its TSS. Notably, elevated c-di-AMP levels diminish RwpL binding affinity for both DNA and RpoA, thereby reversing its regulatory functions and enhancing L. plantarum adhesion to host epithelial cells. Together, our findings uncover a dual and reversible regulatory mechanism through which c-di-AMP modulates bacterial-host interactions in L. plantarum.

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ORGANISM(S): Lactobacillus Plantarum Wcfs1

SUBMITTER: quan Guo

LAB HEAD: Quan Guo

PROVIDER: PXD078286 | Pride | 2026-05-25

REPOSITORIES: Pride

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Project description:Background: Lactobacillus plantarum is found in a variety of fermented foods and as such, consumed for centuries. Some strains are natural inhabitants of the human gastro-intestinal tract and like other Lactobacillus species, L. plantarum has been extensively studied for its immunomodulatory properties and its putative health-promoting effects (probiotic). Being the first line of host defense intestinal epithelial cells (IEC) are key players in the recognition and initiation of responses to gut microorganisms. Results: Using high-density oligonucleotide microarrays we examined the gene expression profiles of differentiated Caco-2 cells exposed to various doses of L. plantarum. In addition, the effects were correlated to monolayer permeability studies and measurement of lactic acid production. A transcriptional dose-dependent IEC response to L. plantarum was found. Incubation of Caco-2 with a low bacterial dose induced a specific response, not due to cytotoxicity or production of lactic acid, including modulation of cell cycle and cell signaling functions. Exposure of Caco-2 cells to larger amounts of bacteria, accompanied by the production of lactic acid and glucose depletion, provoked increased permeability and supposed non-specific defense responses. Conclusions: These results suggest that IEC are able to sense and react to the presence of gut bacteria. This study provides the first description of global transcriptional response of human IEC to a commensal lactic acid bacterium, and it shows the importance of choosing physiological bacterial doses to prevent the observation of non-specific host reactions. Caco-2 cells were exposed for 10h to Lactobacillus. Fourteen samples are analyzed: 4 control Caco-2, 4 Caco-2 exposed to a low dose (10) of Lactobacillus, 4 Caco-2 exposed to a medium dose (100) of Lactobacillus, 2 Caco-2 exposed to a high dose (1000) of Lactobacillus. All 14 RNA samples are labeled with Cy5 and hybridized to a common reference (undifferentiated Caco-2, untreated) RNA labeled with Cy3

			Action	DRS
	RpoA.d.zip	Other
	RpoA.sne	Other
	RwpL.d.zip	Other
	RwpL.sne	Other
	checksum.txt	Txt

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A c-di-AMP receptor mediates epithelial adhesion of Lactiplantibacillus plantarum

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