FolC2-mediated folate metabolism contributes to suppression of inflammation by probiotic Lactobacillus reuteri
Carissa M. Thomas, Delphine M. A. Saulnier, Jennifer K. Spinler, Peera Hemarajata, Chunxu Gao, Sara E. Jones, Ashley Grimm, Miriam A. Balderas, Matthew D. Burstein, Christina Morra, Daniel Roeth, Markus Kalkum and James Versalovic
Version of Record online: 28 JUN 2016 | DOI: 10.1002/mbo3.371
The bifunctional dihydrofolate synthase/folylpolyglutamate synthase type 2 (folC2) gene is necessary for 5,10-methenyltetrahydrofolic acid production by Lactobacillus reuteri, while the folC gene encodes the enzyme responsible for polyglutamylation of 5,10-methenyltetrahydrofolate. The folC2 gene is important for suppression of the proinflammatory cytokine, tumor necrosis factor (TNF), in vitro, and for protection against trinitrobenzene sulfonic acid (TNBS)-induced colitis and mucosal inflammation in vivo. In addition, there is a link between 5,10-methenyltetrahydrofolic acid production and histamine, a known potent immunoregulatory molecule produced by probiotics. Specifically, the folC2 mutant yields diminished expression of the hdc gene cluster, which is responsible for the conversion of l-histidine to histamine as well as diminished histamine production.