Screening and Identification Potent Inhibitors of LAM protein involved in Mycobacterium tuberculosis

Abstract

Mycobacterium tuberculosis, the etiological agent of tuberculosis, spreads by aerosol, mainly infecting alveolar macrophages, by which the bacterium is ingested. Through inhibition of macrophage functions, the bacterium modulates the host immune response. The best-characterized virulence factor of M. tuberculosis, lipoarabinomannan (LAM), is an abundant glycolipid, which is attached to the plasma membrane by a glycosylphosphatidylinositol (GPI) anchor and extends through the cell wall of the bacterium. During uptake of mycobacteria, LAM interacts with the cell membrane of the host macrophage via specific receptors, including the macrophage mannose receptor and complement receptor and can then be detected at multiple sites in the cell. The host cell exports LAM from the phagosome in an exocytosis-like manner, eliciting responses in bystander cells. Host-directed therapies for tuberculosis have been much written about lately. If such therapies are developed, their use is likely to be most significant in patients with multidrug-resistant and extensively drug-resistant tuberculosis. The current work presented in this article could point to in silico identification the inhibitors of LAM protein by molecular docking approach to development novel strategies evaluating structure-based drug designing.