Bioinformatics Analysis to Uncover the Potential Drug Targets Responsible for Mycobacterium tuberculosis Peptidoglycan and Lysine Biosynthesis

Author:

Ayu Eka Pitaloka Dian12,Izzati Afifah1,Rafa Amirah Siti1,Abdan Syakuran Luqman3,Muhammad Irham Lalu45,Darumas Putri Athika6,Adikusuma Wirawan78

Affiliation:

1. Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, Indonesia

2. Center for Translational Biomarker Research, Universitas Padjadjaran, Sumedang, Indonesia

3. Genetics and Molecular Laboratory, Faculty of Biology, Jenderal Soedirman University, Purwokerto, Indonesia

4. Faculty of Pharmacy, Universitas Ahmad Dahlan, Yogyakarta, Indonesia

5. Research Center for Pharmaceutical Ingrediensts and Traditional Medicine, National Research and Inovation Agency (BRIN), South Tangerang, Indonesia

6. Semarang College of Pharmaceutical Sciences (STIFAR), Semarang, Indonesia

7. Department of Pharmacy, Faculty of Health Science, Universitas Muhammadiyah Mataram, Mataram, Indonesia

8. Research Center for Vaccine and Drugs, National Research and Inovation Agency (BRIN), South Tangerang, Indonesia

Abstract

Drug-resistant tuberculosis (TB), which results mainly from the selection of naturally resistant strains of Mycobacterium tuberculosis (MTB) due to mismanaged treatment, poses a severe challenge to the global control of TB. Therefore, screening novel and unique drug targets against this pathogen is urgently needed. The metabolic pathways of Homo sapiens and MTB were compared using the Kyoto Encyclopedia of Genes and Genomes tool, and further, the proteins that are involved in the metabolic pathways of MTB were subtracted and proceeded to protein-protein interaction network analysis, subcellular localization, drug ability testing, and gene ontology. The study aims to identify enzymes for the unique pathways for further screening to determine the feasibility of the therapeutic targets. The qualitative characteristics of 28 proteins identified as drug target candidates were studied. The results showed that 12 were cytoplasmic, 2 were extracellular, 12 were transmembrane, and 3 were unknown. Furthermore, druggability analysis revealed 14 druggable proteins, of which 12 were novel and responsible for MTB peptidoglycan and lysine biosynthesis. The novel targets obtained in this study are used to develop antimicrobial treatments against pathogenic bacteria. Future studies should further shed light on the clinical implementation to identify antimicrobial therapies against MTB.

Funder

Universitas Padjadjaran

Publisher

SAGE Publications

Subject

Applied Mathematics,Computational Mathematics,Computer Science Applications,Molecular Biology,Biochemistry

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