Potential Drug Target Identification in Porphyromonas gingivalis using In-silico Subtractive Metabolic Pathway Analysis

Abstract

Introduction: Porphyromonas Gingivalis (P. gingivalis) a primary periodontal disease pathogen. This bacterium affects sub-gingival tissue and leads to loss of teeth and alveolar bone destruction in the acute stage. In recent years, P. gingivalis is often connected with other diseases such as rheumatoid arthritis, diabetes, Alzheimer’s, and heart disease, though the aetiology is still unclear.
 Objective: The use of commonly available drugs to treat periodontitis results in various side effects, in particular multi-drug resistant strains. As the development of multidrugresistant strains frequently urges the identification of novel drug targets, the aim of this study is to identify specific targets in the narrow spectrum to combat oral pathogens.
 Methodology: This study used a comparative and subtractive pathway analysis approach to identify potential drug targets specific to P. gingivalis.
 Results: The in-silico comparison of the P. gingivalis and Homo sapiens (H. sapiens) metabolic pathways resulted in 13 unique pathogen pathways. A homology search of the 67 enzymes in the unique bacterial pathway using the BLASTp program against the Homo sapiens proteome resulted in fifteen possible targets that are non-homologous to the human proteome. Thirteen genes among 15 potent target encoders are key DEG genes indispensable for P. gingivalis’s survival. A comprehensive analysis of the literature identified three potential therapeutic drug targets.
 Conclusions: The three most relevant drug targets are Arabinose-5-phosphate isomerase, UDP-2,3-diacylglucosamine hydrolase, and Undecaprenyl diphosphatase. Upon corroboration, these targets may give rise to narrow-spectrum antibiotics that can specificallytreat thedental infection.
 Bangladesh Journal of Medical Science Vol.20(4) 2021 p.887-896

Classifying Integrated Signature Molecules in Macrophages of Rheumatoid Arthritis, Osteoarthritis, and Periodontal Disease: An Omics-Based Study

“…Furthermore, research shows that RA and OA significantly alter the oral microbiome [ 3 ]. Periodontal disease (PD) is a chronic inflammatory disease of the tooth and supporting tissues that has been linked to a particular group of bacteria, one of which is Porphyromonas gingivalis [ 9 , 10 , 11 ]. Chronic periodontitis is usually characterized by a heavy infiltrate of inflammatory cells, including macrophages, in the gingival tissue; it results in the resorption of alveolar bone and other tooth-supporting tissues.…”

Predicting Rheumatoid Arthritis Associated Significant Amino-Acid Residues Using Residue-Residue Interaction Analysis

“…P. Gingivalis produces proteinases that cleave protein from the residues of arginine and lysine. These proteinases have many adverse reactions on the host such as reducing the bactericidal effect and reducing host immune responses that proves that bacteria may be a RA-causing agent and proteinases may be a good drug target candidate 9,10 . TNFα (Tumor Necrosis Factor Alpha) is one of RA-Periodontitis connecting links.…”