Extract from Rumex acetosa L. for Prophylaxis of Periodontitis: Inhibition of Bacterial In Vitro Adhesion and of Gingipains of Porphyromonas gingivalis by Epicatechin-3-O-(4β→8)-Epicatechin-3-O-Gallate (Procyanidin-B2-Di-Gallate)

Background: The aerial parts of Rumex acetosa L. have been used in traditional European medicine for inflammatory diseases of the mouth epithelial tissue. The following study aimed to investigate the influence of a proanthocyanidin-enriched extract from R. acetosa extract against the adhesion of Porphyromonas gingivalis (P. gingivalis), a pathogen strongly involved in chronic and aggressive periodontitis. A further goal was to define the bioactive lead structures responsible for a potential antiadhesive activity and to characterize the underlying molecular mechanisms of the antiadhesive effects. Methodology: An extract of R. acetosa (RA1) with a defined mixture of flavan-3-ols, oligomeric proanthocyanidins and flavonoids, was used. Its impact on P. gingivalis adhesion to KB cells was studied by flow cytometry, confocal laser scanning microscopy and in situ adhesion assay using murine buccal tissue. RA1 and its compounds 1 to 15 were further investigated for additional effects on gingipain activity, hemagglutination and gene expression by RT-PCR. Principal Findings: RA1 (5 to 15 μg/mL) reduced P. gingivalis adhesion in a dose-dependent manner to about 90%. Galloylated proanthocyanidins were confirmed to be responsible for this antiadhesive effect with epicatechin-3-O-gallate-(4β,8)-epicatech​in-3’-O-gallate(syn. procyanidin B2-di-gallate) being the lead compound. Ungalloylated flavan-3-ols and oligomeric proanthocyanidins were inactive. RA1 and the galloylated proanthocyanidins strongly interact with the bacterial virulence factor Arg-gingipain, while the corresponding Lys-gingipain was hardly influenced. RA1 inhibited also hemagglutination. In silico docking studies indicated that epicatechin-3-O-gallate-(4β,8)-epicatech​in-3’-O-gallateinteracts with the active side of Arg-gingipain and hemaglutinin from P. gingivalis; the galloylation of the molecule seems to be responsible for fixation of the ligand to the protein. In conclusion, the proanthocyanidin-enriched extract RA1 and its main active constituent procyanidin B2-di-gallate protect cells from P. gingivalis infection by inhibiting bacterial adhesion to the host cell. RA1 and procyanidin B2-di-gallate appear to be promising candidates for future cytoprotective preparations for oral mouth care products

New Mycobacterium tuberculosis Complex Sublineage, Brazzaville, Congo

Tuberculosis is a leading cause of illness and death in Congo. No data are available about the population structure and transmission dynamics of the Mycobacterium tuberculosis complex strains prevalent in this central Africa country. On the basis of single-nucleotide polymorphisms detected by whole-genome sequencing, we phylogenetically characterized 74 MTBC isolates from Brazzaville, the capital of Congo. The diversity of the study population was high; most strains belonged to the Euro-American lineage, which split into Latin American Mediterranean, Uganda I, Uganda II, Haarlem, X type, and a new dominant sublineage named Congo type (n = 26). Thirty strains were grouped in 5 clusters (each within 12 single-nucleotide polymorphisms), from which 23 belonged to the Congo type. High cluster rates and low genomic diversity indicate recent emergence and transmission of the Congo type, a new Euro-American sublineage of MTBC

Type 2 T cell responses against distinct epitopes of the desmoglein 3 ectodomain in pemphigus vulgaris.

Pemphigus vulgaris (PV) is an autoimmune blistering disorder of the skin and/or mucous membranes caused by IgG autoantibodies which predominantly target two transmembrane desmosomal cadherins, desmoglein (Dsg)1 and Dsg3. Dsg-specific T cells play a central role in PV pathogenesis as they provide help to autoreactive B cells for autoantibody production. We here characterized Dsg3-specific peripheral T cells in a cohort of 52 PV patients and 41 healthy controls (HC) with regard to cytokine profile and epitope specificity. By ELISpot analysis, type 2 T cells reactive with the Dsg3 ectodomain were significantly increased in PV patients compared to HC. By dextramer analysis, CD4+ T cells specific for an epitope within the extracellular domain of Dsg3, Dsg3(206-220), were found at significantly higher frequencies in PV patients than in HLA-matched HC. T cell recognition of two distinct Dsg3 epitopes, i.e. Dsg3(206-220) and Dsg3(378-392), correlated significantly suggesting a synergistic effect in B cell help. Immunization of HLA-DRB1*04:02-transgenic PV mice with the same set of Dsg3 peptides induced pathogenic Dsg3-specific IgG antibodies which induced loss of keratinocyte adhesion in vitro. Thus, Dsg3 peptide-specific T cells are of particular interest as surrogate marker of disease activity and potential therapeutic targets in PV