RRC ID 51612
Author Sumitomo T, Nakata M, Higashino M, Yamaguchi M, Kawabata S.
Title Group A Streptococcus exploits human plasminogen for bacterial translocation across epithelial barrier via tricellular tight junctions.
Journal Sci Rep
Abstract Group A Streptococcus (GAS) is a human-specific pathogen responsible for local suppurative and life-threatening invasive systemic diseases. Interaction of GAS with human plasminogen (PLG) is a salient characteristic for promoting their systemic dissemination. In the present study, a serotype M28 strain was found predominantly localized in tricellular tight junctions of epithelial cells cultured in the presence of PLG. Several lines of evidence indicated that interaction of PLG with tricellulin, a major component of tricellular tight junctions, is crucial for bacterial localization. A site-directed mutagenesis approach revealed that lysine residues at positions 217 and 252 within the extracellular loop of tricellulin play important roles in PLG-binding activity. Additionally, we demonstrated that PLG functions as a molecular bridge between tricellulin and streptococcal surface enolase (SEN). The wild type strain efficiently translocated across the epithelial monolayer, accompanied by cleavage of transmembrane junctional proteins. In contrast, amino acid substitutions in the PLG-binding motif of SEN markedly compromised those activities. Notably, the interaction of PLG with SEN was dependent on PLG species specificity, which influenced the efficiency of bacterial penetration. Our findings provide insight into the mechanism by which GAS exploits host PLG for acceleration of bacterial invasion into deeper tissues via tricellular tight junctions.
Volume 7
Pages 20069
Published 2016-1-29
DOI 10.1038/srep20069
PII srep20069
PMID 26822058
PMC PMC4731814
MeSH Bacterial Proteins / genetics Bacterial Proteins / metabolism* Bacterial Translocation / genetics Caco-2 Cells Carrier Proteins / genetics Epithelial Cells / metabolism Epithelial Cells / microbiology Host-Pathogen Interactions / genetics* Humans MARVEL Domain Containing 2 Protein / genetics MARVEL Domain Containing 2 Protein / metabolism* Mutagenesis, Site-Directed Phosphopyruvate Hydratase / genetics Phosphopyruvate Hydratase / metabolism* Plasminogen / genetics Plasminogen / metabolism* Species Specificity Streptococcus pyogenes / metabolism Streptococcus pyogenes / pathogenicity Surface Plasmon Resonance Tight Junctions / metabolism Tight Junctions / microbiology
IF 4.011
Times Cited 14
Human and Animal Cells CACO-2(RCB0988)