Porphyromonas gingivalis – an oral keystone pathogen challenging the human immune system
|PhD ceremony:||Mr T. (Tim) Stobernack|
|When:||July 01, 2019|
|Supervisors:||prof. dr. J.M. (Jan Maarten) van Dijl, Prof. A.J. van Winkelhoff, prof. dr. P. (Peter) Heeringa|
|Co-supervisor:||dr. J. (Hannie) Westra|
|Where:||Academy building RUG|
|Faculty:||Medical Sciences / UMCG|
The human mouth is colonized by hundreds of different microorganisms. While most are harmless, a few of them cause disease in our oral cavity and beyond. One of these pathogens is called Porphyromonas gingivalis. This bacterium is known to be involved in periodontitis, an inflammatory disease affecting the tissues surrounding our teeth. Intriguingly, periodontitis and P. gingivalis are associated with the autoimmune disease rheumatoid arthritis. Individuals with periodontitis have a two-fold higher risk of developing rheumatoid arthritis than individuals with healthy gum tissues. The research described in this thesis revolved around the question how P. gingivalis interacts with our immune defenses, in particular the innate defenses, and how these interactions may subsequently lead to autoimmunity. An important observation was that P. gingivalis invariably secretes an enzyme called PPAD that converts the charge of other proteins from positive to neutral. This neutralization concerns not only bacterial proteins, but also human proteins. Intriguingly, the positive charge of human antimicrobial peptides is key for their bactericidal activity, and a major finding was therefore that PPAD ‘neutralizes’ such peptides. PPAD can also be linked to rheumatoid arthritis, because the respective auto-antibodies target neutralized proteins. A key conclusion from the present research is that PPAD is a central factor that allows P. gingivalis to escape from our immune defenses. As a consequence, this enzyme potentially contributes to the onset of rheumatoid arthritis. Accordingly, P. gingivalis and PPAD may be considered as candidate drug targets to prevent the onset of this severe autoimmune disease.