Mechanisms of Porphyromonas gingivalis sialoglycoproteases in virulence andhost interactions

Loma Linda Veterans Assn Research & Educ, Redlands CA

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Abstract

The microenvironment of the periodontal pocket contain an abundance of sialylated glycoproteins. P. gingivalis a key stone pathogen has been shown to enable the emergence of dysbiotic oral bacterial communities, hence play an important role in periodontal pathogenesis. They also express sialoglycorptoeases which break down the terminal sialic acids in the sialoglycoproteins. This breakdown contributes to many important biological functions by either exposing or masking the interacting receptors. Studies have shown the importance of these enzymes in virulence and pathogenesis of P. gingivalis and also in other bacteria. Our preliminary in vitro data showed the involvement of P. gingivalis sialoglycoproteases (PG-Sgps) (PG0778 & PG1724) in virulence modulation and show binding specificity to common glycoprotein subtypes found in eukaryotic cells. However, there is still a significant gap in knowledge of how PG-Sgps orchestrate host- pathogen interaction and virulence leading to dysbiosis. Our central hypothesis is that PG-Sgps are involved in virulence regulation and contribute to host interaction through surface glycan modifications of specific virulence glycoproteins and mediate immune evasion through interactions with cell surface sialylated ligands in neutrophils. We will test our hypothesis by completion of the following specific aims: (1). Identify the functional role of P. gingivalis sialoglycoproteases and surface glycan changes influencing pathogenic potential of the organism. (2).Study the in vivo virulence of P. gingivalis sialoglycoproteases and identify PG-Sgp mediated neutrophil interactions involved in dysregulation of innate immunity. This work will advance our understanding of P. gingivalis virulence and pathogenicity by studying the functional role of PG-Sgps through identification of specific glycan modification in two important virulence determinants of P. gingivalis. And to study, how PG-Sgps interact with neutrophils influencing the pathogenic potential of P. gingivalis. This will eventually lead us to expand our scope for understanding specific sialic acid ligand interactions and their role in immune evasion and subversion of P. gingivalis. This study will lead us to design potential therapeutic targets against the sialic acid specific ligands. Hence, will pave the way for future pharmacological prevention of P. gingivalis infection. .