An In silico analysis to study the molecular host-microbe in tuberculosis infection: disturb the immune system by interacting with CXCR۸ and TLR۲

BACKGROUND AND OBJECTIVESTuberculosis is a bacterial infectious disease caused by Mycobacterium tuberculosis (Mtb), which by ۱۰.۴ million new cases and nearly ۱.۷ million deaths in ۲۰۱۷, causing more deaths worldwide than any other infectious agent. Mtb adopt diverse strategies to survive and invade human immunity. These mechanisms make the pathogen resistant to presently available drugs, a primary contributing factor in the failure to control the spread of tuberculosis. It has been shown gthat interacting bacterial proteins with human proteins can change signaling, metabolic pathways, and cellular processes in the infected host. This study aimed to use bioinformatics tools to understand how Mtb proteins develop infection in human cells.MATERIALS AND METHODSTo identify bacterial proteins that interact with human proteins, ImitateDB database was used. The Mtb (strain ATCC ۲۵۶۱۸ / H۳۷Rv) was selected in this database, and interacting proteins with human cells were recognized. Host interactor protein IDs were extracted as well. These codes were converted into gene symbols through the BioDBnet database, and these proteins' functions were determined using string and EnrichR databases and string.RESULTS AND DISCUSSIONThe ImitateDB showed Mtb proteins including serA (D-۳-phosphoglycerate dehydrogenase), ahcY (Adenosylhomocysteinase), atsG (arylsulphatase), glmU (N-acetylglucosamine-۱-phosphate uridyl transferase) mainly interact with CXCR۸(Chemokine (C-X-C motif) receptor ۸) protein while PE۳۵ and PPE۶۸ bind to TLR۲(Toll-like receptors ۲) protein in human cells. As presented in Figure ۱, these two proteins are also related to ۱۰ human proteins through different motifs. Functional analysis by EnrichR revealed that all these human genes are significantly involved in diseases associated with Toll-like signaling and MyD۸۸(Myeloid differentiation primary response ۸۸) protein deficiency. (Figure ۲). Various studies have shown that disruptions of TLR۲ and MyD۸۸ signaling pathways interfere with other intrinsic intracellular antimicrobial pathways, such as autophagy and functional vitamin D receptor (VDR) signaling, in addition to causing acute inflammation and lung injury.CONCLUSIONBioinformatics approaches can be used for understanding of the molecular mechanisms of tuberculosis pathogenesis and host protective immunity against tuberculosis infections, and to facilitate vaccine design and development.

کلیدواژه ها:

Mycobacterium tuberculosis ، Bioinformatics analysis ، protein-protein interaction ، molecular mechanism