Comparative Analysis of Host-Pathogen Protein-Protein Interactions between Human and Various Strains of Mycobacterium...

Tuberculosis remains a substantial health threat globally, despite decades having elapsed since the identification of its causative agent, Mycobacterium tuberculosis. Approximately 35% of the global population is sub-clinically infected, leading as one of the primary causes of human mortality. The increased prevalence of drug-resistant strains of Mtb necessitates identification of important drug targets. Therefore, the aim of the study was to comparatively analyze the protein-protein interactions between the host and the pathogen (Mycobacterium tuberculosis) to uncover the conserved molecular mechanisms of infection, providing insight into strain-specific variations.

One of the major problems is the diverse spectrum of diseases caused by different Mtb. To date, most research has their attention on a specific pathogenic strain. Therefore, to screen common and effective drug targets of different strains, we compared the protein-protein interactions of four virulent strains (H37Rv, CDC1551, CAS/NITR204, and Erdman) and one a virulent strain (H37Ra) of Mtb with its human host. Here, the interolog method was adopted to identify the biomolecular-interactions between Mtb and its human host.

As a result, an interaction network has been developed, and the target has been screened through multiple parameters, such as the highest interacting partners, virulent factors, subcellular localization, and predicted protein interactions.

This study substantially resulted in the identification of potential drug targets, ATP synthase subunit alpha and gamma, and chaperone proteins DNAK and HTPG.