NOVEL APPROACH TO TARGET PERIODONTITIS AND ATHEROSCLEROSIS BY INHIBITION OF ARGININE GINGIPAINS

Abstract

Human mouth flora has large number of microorganisms and periodontal complications leads to Coronary heart disease (CHD). Periodontitis which is caused by consortia of microbes such as Porphyromonas gingivalis, Aggrigatibacter actinomycetemcomitans, Chlamydia pneumoniae, Campylobacter rectus and entry of these microbes in blood vessel initiate a proinflammatory response. Also antigen presenting cells like macrophages and dentritic cells activate the adenosine receptors (A2bAR and A3AR) and atheroma formation, which leads to atherosclerosis. There is twenty five percent hike in the risk of CHD connected with periodontal disease. The nucleotide sequence from Porphyromonas gingivalis strain ATCC33277, which is the main causative agent of periodontitis were blasted against other microbes associated with dental caries and periodontal disease. The protein sequence of Transglutaminase2 (TG2), which forms tight association with fibronectin(FN), was retrieved and the protein binding regions/sites were predicted using PredictProtein tool. The adhesion molecule- Gingipains R(RgpA and RgpB) both showed similarity in binding sites among TG2 and FN. The predicted B cell epitope of RgpA and RgpB using various tools such as ABCpred Prediction Server, Discotope, Bepipred Linear Epitope Prediction, were subjected to threshold structure prediction. Flexibility, antigencity and surface accessibility were predicted. Further T cell epitope stretch was predicted, that was encompassed in B cell epitope stretch which triggers both CMI and humoral immune response. The T cell epitopes were identified using tools like Multipred, NetMHC, CTLpred, PrediVac and TAP binding region and proteosomal cleavage sites are predicted through TAPPred and PAPROC respectively. The population coverage prediction is also done using PrediVac for identifying the prevalent peptides in different geographical location. Ultimately two epitopes were obtained which inhibit arginine gingipains and predicted as a probable vaccine candidate for periodontitis causing atherosclerosis.