<i>Porphyromonas gingivalis</i> induces penetration of lipopolysaccharide and peptidoglycan through the gingival epithelium via degradation of junctional adhesion molecule 1

Published on 2019-11-07T18:59:58Z (GMT) by
<div><p><i>Porphyromonas gingivalis</i> is a major pathogen in severe and chronic manifestations of periodontal disease, which is one of the most common infections of humans. A central feature of <i>P</i>. <i>gingivalis</i> pathogenicity is dysregulation of innate immunity at the gingival epithelial interface; however, the molecular basis underlying <i>P</i>. <i>gingivalis</i>–dependent abrogation of epithelial barrier function remains unknown. Gingival epithelial cells express junctional adhesion molecule (JAM1), a tight junction–associated protein, and JAM1 homodimers regulate epithelial barrier function. Here we show that Arg-specific or Lys-specific cysteine proteases (gingipains) secreted by <i>P</i>. <i>gingivalis</i> can specifically degrade JAM1 at K134 and R234 in gingival epithelial cells, resulting in permeability of the gingival epithelium to 40 kDa dextran, lipopolysaccharide (LPS), and proteoglycan (PGN). A <i>P</i>. <i>gingivalis</i> strain lacking gingipains was impaired in degradation of JAM1. Knockdown of JAM1 in monolayer cells and a three-dimensional multilayered tissue model also increased permeability to LPS, PGN, and gingipains. Inversely, overexpression of JAM1 in epithelial cells prevented penetration by these agents following <i>P</i>. <i>gingivalis</i> infection. Our findings strongly suggest that <i>P</i>. <i>gingivali</i>s gingipains disrupt barrier function of stratified squamous epithelium via degradation of JAM1, allowing bacterial virulence factors to penetrate into subepithelial tissues.</p></div>

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Takeuchi, Hiroki; Sasaki, Naoko; Yamaga, Shunsuke; Kuboniwa, Masae; Matsusaki, Michiya; Amano, Atsuo (2019): Porphyromonas gingivalis induces penetration of lipopolysaccharide and peptidoglycan through the gingival epithelium via degradation of junctional adhesion molecule 1. PLOS Pathogens. Collection. https://doi.org/10.1371/journal.ppat.1008124