Periodontitis is a highly prevalent chronic inflammatory disease characterized by the destruction of tooth-supporting tissues, ultimately leading to tooth loss. Microorganisms are the causative agents of periodontitis with a key role for the oral bacterium Porphyromonas gingivalis. Intriguingly, P. gingivalis is also linked to several major systemic diseases, including rheumatoid arthritis, Alzheimer’s disease and certain cancers, highlighting its clinical relevance beyond the oral cavity. The pathogenicity of P. gingivalis relies on a diverse repertoire of virulence factors, including so-called lipopolysaccharides (LPS) on the bacterial cell surface and protein-degrading or -modifying enzymes, which are bundled in excreted outer membrane vesicles (OMVs) that are pinched off from the bacterial surface.
The aim of the present PhD research of Dongyi Xu was to dissect the roles of these components in the subversion of the human host defenses by P. gingivalis. Particular attention was attributed to the roles of LPS, a protein-modifying enzyme known as PPAD, and the OMVs excreted by P. gingivalis. In addition, the interactions between P. gingivalis and another oral pathogen, the bacterium Fusobacterium nucleatum, were explored. The results show that PPAD and the atypical structure of P. gingivalis LPS allow this bacterium to escape from our immune defenses.
Additionally, the presence of F. nucleatum was shown to increase the ability of P. gingivalis to invade human cells, thereby enhancing its virulence. Altogether, this study highlights PPAD, proteolytic enzymes and LPS as critical virulence determinants of P. gingivalis and identifies them as promising targets for prevention or treatment of periodontitis and associated systemic diseases.
