Porphyromonas gingivalis, a keystone pathogen in periodontitis has been strongly implicated in the initiation and exacerbation of rheumatoid arthritis (RA) due to its array of extracellular virulence factors. The arginine- and lysine-specific gingipain proteinases of P. gingivalis damage host tissue and dysregulate the host immune response. P. gingivalis, uniquely amongst bacteria, produces a peptidylarginine deiminase (PPAD) which citrullinates C-terminal arginine residues of bacterial and host peptides. This results in them being recognised as foreign bodies, triggering an immune response that can cross-react with the host’s own citrullinated proteins, breaking immune tolerance and producing harmful autoantibodies. P. gingivalis produces distinct bioactive lipids, including phosphorylated dihydroceramide lipids (sphingolipids) and serine dipeptide lipids which both promote osteoclast differentiation resulting in bone resorption. Critically, P. gingivalis produces membrane vesicles (MVs) enriched in these virulence factors and sphingolipids which enable MVs to evade the host immune response by limiting the inflammatory response of macrophages and neutrophils. We hypothesise that it is MVs that are continuously released from P. gingivalis in subgingival plaque during chronic periodontitis progression over years that enter the bloodstream and cause pathology elsewhere in the body. We will use both in vitro and in vivo models of RA and our extensive knowledge of P. gingivalis MVs to examine their role in RA initiation. We have an array of P. gingivalis mutants missing key virulence factors (including PPAD, gingipains, sphingolipid, modified lipid A) available in our purpose-built laboratory, that will be used to determine how MVs contribute to disease causation.

Dr

Benny Shah

Postdoctoral Research Fellow

Melbourne Dental School

Dr

Benny Shah

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Faculty of Medicine, Dentistry and Health Sciences

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Benny Shah

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