Identification of Potential Drug Targets in Helicobacter pylori Strain HPAG1 by <i>in silico</i> Genome Analysis

Abstract

Helicobacter pylori colonizes the stomach, causing gastritis, peptic ulcers and gastric carcinoma. Drugs for treatment of H. pylori relieve from gastritis or pain but are not specific to H. pylori. Therefore, there is an immediate requirement for new therapeutic molecules to treat H. pylori. Current study investigates identification of drug targets in the strain HPAG1 of H. pylori by in silico genome analysis. Genome of HPAG1 was reconstructed for metabolic pathways and compared with Homosapien sapiens to identify genes which are unique to H. pylori. These unique genes were subjected to gene property analysis to identify the potentiality of the drug targets. Among the total number of genes analysed in H. pylori strain HPAG1, nearly 542 genes qualified as unique molecules and among them 29 were identified to be potential drug targets. Co/Zn/Cd efflux system membrane fusion protein, Ferric sidephore transport system and biopolymer transport protein EXbB were found to be critical drug targets to H. pylori HPAG1. Five genes (superoxide dismutase, HtrA protease/chaperone protein, Heatinducible transcription repressor HrcA, HspR, transcriptional repressor of DnaK operon, Cobalt-zinccadmium resistance protein CzcA) of the 29 predicted drug targets are already experimentally validated either genetically or biochemically lending credence to our unique approach.

Flavodoxins as Novel Therapeutic Targets against Helicobacter pylori and Other Gastric Pathogens

“…Some of them are detailed in Table 1, and the more relevant ones are described below. Coenzyme A biosynthesis [35,36] Carbon starvation protein A Starvation response, utilization of peptides, and host-pathogen interactions [37] Methylthiotransferase (MiaB) Protein synthesis [37] Ribosomal RNA small subunit methyltransferase E Protein synthesis [37] Ribosomal protein L11 methyltransferase Protein synthesis [37] Tetrapyrrole (Corrin-Porphyrin) methylase family protein Protein synthesis [37] Peptide chain release factor 1 Protein synthesis [37] Fumarate reductase (FrdA, FrdB, and FrdC)…”

“…Krebs cycle and anaerobic respiration [33,38] Glu-tRNA Gln amidotransferase, subunits A (GatA), B (GatB), and C (GatC) Protein synthesis [26,33] Coenzyme A biosynthesis [35,36] Carbon starvation protein A Starvation response, utilization of peptides, and host-pathogen interactions [37] Methylthiotransferase (MiaB) Protein synthesis [37] Ribosomal RNA small subunit methyltransferase E Protein synthesis [37] Ribosomal protein L11 methyltransferase Protein synthesis [37] Tetrapyrrole (Corrin-Porphyrin) methylase family protein Protein synthesis [37] Peptide chain release factor 1 Protein synthesis [37] Fumarate reductase (FrdA, FrdB, and FrdC) Krebs cycle and anaerobic respiration [33,38] Glu-tRNA Gln amidotransferase, subunits A (GatA), B (GatB), and C (GatC) Protein synthesis [26,33] Helicase-nuclease DNA Repair Enzymes (AddAB) DNA damage reparation [39,40] Cytochrome C-type biogenesis protein CcdA Cytochrome C synthesis [37] Cytochrome C oxidase, subunits CcoN, CcoO, CcoP and CcoQ ATP synthesis [37] Flavodoxin (Fld) Oxidative decarboxylation of pyruvate [28,[41][42][43] Table 1. Cont.…”

“…into host cells) [80,83] HopQ adhesin (outer membrane protein) Adhesion to host cells and translocation of CagA into host cells [84] Vacuolating cytotoxin (VacA) Cellular vacuolation, apoptosis and inhibition of cell cycle progression and host immune response [81,82,85,86] Blood group antigen binding adhesin (BabA) Adhesion to host cells [80][81][82] High temperature requirement A (HtrA) Chaperone and proteolytic activities (intercellular adhesion cleavage) [37,85,87]…”

Medicinal Chemistry and Drug Designing

“…Present day drug discovery and development follows a very systematic and complex process to generate Food and Drug Administration (FDA) approved drugs. The drug discovery process starts with identification and validation of drug targets for a particular disease [1][2][3][4][5] . Medicinal chemists design a new molecule to the established target using Computer Assisted Drug Designing (CADD).…”

Identification of Drug Target Properties and its validation on Helicobacter pylori

“…Yadav et al [7] showed the targetable virulence factors for pneumonia using bioinformatics tools. The other workers predicted drug targets for Helicobacter pylori using various in silico approaches [8,9]. Here, we have developed a new method for identification of drug target that is based on the already available drug targets.…”