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A comparative proteomic approach using metabolic pathways for the identification of potential drug targets against Helicobacter pylori

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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.

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Acknowledgements

The authors would like to acknowledge the funds provided by the Pakistan Science Foundation.

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Authors and Affiliations

  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

    Reaz Uddin & Waqar Khalil

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  1. Reaz Uddin
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  2. Waqar Khalil
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Correspondence to Reaz Uddin.

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Uddin, R., Khalil, W. A comparative proteomic approach using metabolic pathways for the identification of potential drug targets against Helicobacter pylori. Genes Genom 42, 519–541 (2020). https://doi.org/10.1007/s13258-020-00921-z

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