生化学と分析生化学

概要

Identification of Putative Drug Targets and Vaccine Candidates for Pathogens Causing Atherosclerosis

Kanipakam Hema, Vani Priyadarshini I, Dibyabhaba Pradhan, Manne Munikumar, Swargam Sandeep, Swargam Sandeep, Natarajan Pradeep, Suchitra MM and Amineni Umamaheswari

Atherosclerosis is a chronic inflammatory artery disease, responsible for both cardiovascular (heart) and cerebrovascular (brain) stroke with high morbidity and mortality worldwide. Infectious pathogens such as Chlamydophila pneumoniae, Porphyromonas gingivalis and Helicobacter pylori are shown to be associated with the disease in recent epidemiological studies. Therefore, identification of common drug targets and vaccine candidates against these three pathogens would be vital towards therapy and management of atherosclerosis. Chlamydophila pneumonia was selected as a reference organism due to its predominant role in atherosclerosis. Implementing comparative genomic approach, subtractive genomic approach, metabolic pathway analysis, non-homologous gut flora analysis and domain search analysis, 35 common putative drug targets were identified against pathogens of atherosclerosis. Subcellular localization studies were performed and identified UvrABC protein as vaccine candidate. Metabolic pathway analysis has showed that, out of 35 drug targets, 14 enzymes were participating in key pathways linked to pathogen’s survival, proliferation and pathogenesis without any alternative mechanism to synthesize the product. The gut microbiota analysis was performed to identify the drug targets which do not affect the microbiota in the humans. Domain search was performed for the identified 14 drug targets using Pfam and SMART databases and protein network analysis was carried out using STRING and Cytoscape v3.2.0. The drug targets and vaccine candidates proposed in the present study would serve as basis to design potent inhibitors and subunit vaccines through in silico approach for combating atherosclerosis caused by infectious pathogens.