Protein Integrated Network Analysis to Reveal Potential Drug Targets Against Extended Drug-Resistant Mycobacterium tuberculosis XDR1219

• Published in: Molecular biotechnology 2021-12, Vol.63 (12), p.1252-1267
• Main Authors: Zahra, Noor ul Ain, Jamil, Faiza, Uddin, Reaz
• Format: Article
• Language: English
• Subjects: Bacterial Proteins - drug effects; Bacterial Proteins - metabolism; Biochemistry; Bioinformatics; Biological Techniques; Biotechnology; Cell Biology; Chemistry; Chemistry and Materials Science; Computational Biology - methods; Computer applications; Drug Discovery; Drug resistance; Drug Resistance, Bacterial - drug effects; Human Genetics; Metabolic pathways; Molecular Targeted Therapy; Mycobacterium tuberculosis; Mycobacterium tuberculosis - drug effects; Mycobacterium tuberculosis - metabolism; Network analysis; Original Paper; Pathogenesis; Protein Interaction Maps - drug effects; Protein Science; Proteins; Proteomes; Proteomics - methods; Therapeutic targets; Tuberculosis; Virulence
• ISSN: 1073-6085; 1559-0305
• DOI: 10.1007/s12033-021-00377-w

The reconstruction and analysis of the protein–protein interaction (PPI) network is a powerful approach to understand the complex biological and molecular functions in normal and disease states of the cell. The interactome of most organisms is largely unidentified except some model organisms. The current study focused on the construction of PPI network for the human pathogen Mycobacterium tuberculosis (MTB)-resistant strain XDR1219 using computational methods. In this work, a bioinformatics approach was employed to reveal potential drug targets. The pipeline adopted the combination of an extensive integrated network analysis that led to identify 22 key proteins involved in drug resistance, resistant metabolic pathways, virulence, pathogenesis and persistency of the infection. The MTB XDR1219 interactome consists of 11,383 non-redundant PPIs among 1499 proteins covering 38% of the entire MTB XDR1219 proteome. The overall quality of the network was assessed and topological parameters of the PPI were calculated. The predicted interactions were functionally annotated and their relevance was assessed with the functional similarity. The study attempts to present the interactome of previously unidentified MTB XDR1219 and revealed potential drug targets that can be further explored by scientific community.