Reaz Uddin1, Waqar Khalil2. 1. Lab 103 PCMD ext. Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Science, University of Karachi, Karachi, 75270, Pakistan. mriazuddin@iccs.edu. 2. Lab 103 PCMD ext. Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Science, University of Karachi, Karachi, 75270, Pakistan.
Abstract
BACKGROUND: Helicobacter pylori is the most highlighted pathogen across the globe especially in developing countries. Severe gastric problems like ulcers, cancers are associated with H. pylori and its prevalence is widespread. Evolution in the genome and cross-resistance with different antibiotics are the major reason of its survival and pandemic resistance against current regimens. OBJECTIVES: To prioritize potential drug target against H. pylori by comparing metabolic pathways of its available strains. METHODS: We used various computational tools to extract metabolic sets of all available (61) strains of H. pylori and performed pan genomics and subtractive genomics analysis to prioritize potential drug target. Additionally, the protein interaction and detailed structure-based studies were performed for further characterization of protein. RESULTS: We found 41 strains showing similar set of metabolic pathways. However, 19 strains were found with unique set of metabolic pathways. The metabolic set of these 19 strains revealed 83 unique proteins and BLAST against human proteome further funneled them to 38 non-homologous proteins. The druggability and essentiality testing further converged our findings to a single unique protein as a potential drug target against H. pylori. CONCLUSION: We prioritized one protein-based drug target which upon subject to applied protocol was found as close homolog of the Saccharopine dehydrogenase. Our study has opened further avenues of research regarding the discovery of new drug targets against H. pylori.
BACKGROUND:Helicobacter pylori is the most highlighted pathogen across the globe especially in developing countries. Severe gastric problems like ulcers, cancers are associated with H. pylori and its prevalence is widespread. Evolution in the genome and cross-resistance with different antibiotics are the major reason of its survival and pandemic resistance against current regimens. OBJECTIVES: To prioritize potential drug target against H. pylori by comparing metabolic pathways of its available strains. METHODS: We used various computational tools to extract metabolic sets of all available (61) strains of H. pylori and performed pan genomics and subtractive genomics analysis to prioritize potential drug target. Additionally, the protein interaction and detailed structure-based studies were performed for further characterization of protein. RESULTS: We found 41 strains showing similar set of metabolic pathways. However, 19 strains were found with unique set of metabolic pathways. The metabolic set of these 19 strains revealed 83 unique proteins and BLAST against human proteome further funneled them to 38 non-homologous proteins. The druggability and essentiality testing further converged our findings to a single unique protein as a potential drug target against H. pylori. CONCLUSION: We prioritized one protein-based drug target which upon subject to applied protocol was found as close homolog of the Saccharopine dehydrogenase. Our study has opened further avenues of research regarding the discovery of new drug targets against H. pylori.
Authors: Paula Roszczenko-Jasińska; Marta Ilona Wojtyś; Elżbieta K Jagusztyn-Krynicka Journal: Appl Microbiol Biotechnol Date: 2020-10-14 Impact factor: 4.813