[F31] Enterococcal Stimulation of the Mucosal IgA Response

Ente: National Institute of Allergy and Infectious Diseases

Scadenza: 2029-04-30

Importo max: 42.995 EUR

Paese: US

Descrizione

PROJECT SUMMARY Enterococcus faecalis is a Gram-positive bacterium that is found in the gastrointestinal (GI) tract of healthy humans. However, disruption of gut-immune homeostasis can enable the overgrowth of E. faecalis, allowing it to translocate the intestinal epithelium, spread to the bloodstream and other organs, and cause serious conditions such as infective endocarditis. Enterococcal polysaccharide antigen (EPA) is a cell wall- attached glycan and virulence factor that is present in both nosocomial and commensal strains of E. faecalis. Mutations in the genes encoding EpaS and EpaX, glycosyltransferases necessary the complete biosynthesis of EPA polymers, significantly impair E. faecalis GI tract colonization. While previous studies have investigated interactions between EPA and the innate immune response, interactions between EPA and the adaptive immune response are understudied. Our lab recently discovered that germ-free (GF) C57BL/6 mice mono-colonized with wild-type (WT) E. faecalis exhibit significantly increased immunoglobulin A (IgA) binding compared to a ∆epaS mutant. Secretory IgA (sIgA) in the gut has a defined role in maintaining gut homeostasis by binding to bacteria and their toxins, thereby preventing pathogen epithelial translocation and neutralizing toxins. Recent studies have revealed additional roles of gut sIgA, including enabling commensal colonization, regulating microbiota gene expression, and promoting interbacterial symbiosis during gut inflammation. Since certain E. faecalis strains occupy the GI tract as commensals, it is unclear whether sIgA binding to E. faecalis enables its colonization or plays a role in the translocation of E. faecalis across the epithelial barrier. By evaluating the molecular interaction between EPA, a crucial virulence factor of E. faecalis, and IgA, the most abundant secretory antibody in the gut, this work will improve our understanding of the function of EPA in E. faecalis during host-pathogen interactions. It may also shed light on how commensal enterococci transition to become opportunistic pathogens. Istituzione: UNIVERSITY OF COLORADO DENVER PI: Joanna Chau Progetto: 1F31AI197797-01

Settori: National Institute of Allergy and Infectious Diseases

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