Characterization of host-parasite interactions between the oral mucosa and the protozoan Entamoeba gingivalis that drive tissue invasion, destruction and microbial dysbiosis

• Applicant: Professor Dr. Arne Schäfer
• Subject Area: Dentistry, Oral Surgery
• Term: from 2020 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 437460519

Periodontitis (PD) is a common inflammatory disease of the oral cavity, with prevalence rates of 11% in Western countries for severe forms. The course of disease leads to destruction of the connective tissue of the teeth and alveolar bone with subsequent tooth loss. PD is characterized by a microbial shift of the subgingival microbiota. The dysbiosis chronically activates the immune system in predisposed individuals leading to destruction of the periodontium. Identification of a specific pathogen that drives dysbiosis, inflammation and tissue destruction would help in the diagnosis and treatment of PD. In contrast to the generally reduced microbial diversity at the sites of oral inflammation, the prevalence of the protozoan Entamoeba ginigivalis (E. gingivalis) is significantly increased, contributing the second most abundant rRNA found in PD after human rRNA. In our preliminary works, we detected E. gingivalis in 76% of inflamed periodontal pockets and in 20% of the healthy oral cavities, and gave evidence that it triggers inflammation, drives destruction of the oral barrier and is able to invade the oral mucosa where it moves and feeds on host cells. Similar to the colonic parasite E. histolytica, to which it is related, our preliminary data indicated that the invasion strategies of this oral Entamoeba species involve mucin and matrix metalloproteinase (MMP) function. The exocytosis of these proteins is orchestrated by the vesicle associated membrane proteins VAMP8 and VAMP3, respectively. Both are published genetic risk loci of PD. To elucidate the defense and infection mechanisms in detail, we will characterize the role of VAMP8 and VAMP3 in the pathogenicity of E. gingivalis infection, define the mucin and MMP-depending tissue invasion and destruction strategies, and identify the interrelation of this protozoan parasite with oral antimicrobial peptides. Additionally, we will perform de novo sequencing of the E. gingivalis genome. We will further identify the oral bacteria that are preferentially phagocytosed by E. gingivalis. Because the pathogenic mechanisms of this parasite could be an important microbial trigger of destructive forms of PD that cannot be explained by current etiological concepts, and could also contribute to an increased risk for PD-associated systemic diseases like oral cancer and cardiovascular diseases, we anticipate our results highly relevant to dental and general medicine.

• DFG Programme: Research Grants