LIPOPROTEIN SYNTHESIS IN MYCOBACTERIUM TUBERCULOSIS INFECTION

 

Tuberculosis (TB) is caused by a bacterium called mycobacterium tuberculosis. The bacterium usually attack the lungs, however, TB bacteria can attack any part of the body such as the kidney, spine and brain. In some cases, people infected with TB bacteria do not show any symptom. In such cases, the health condition is called latent TB infection (LTBI).

Childhood TB contributes to approximately 15 -40% of all TB cases and is usually acquired from contact with infectious adult. The high rate of TB transmission among children can be attributed to population density and prolonged diagnostic delay in endemic areas. Majority of the childhood TB cases and deaths occur in low income nations.

Spread of mycobacterium tuberculosis infection

TB bacteria are airborne and are spread from person to person. People living in clustered areas with limited ventilation are at high risk of contracting TB infection. Once a person is infected with TB bacteria, the bacteria settle in the lungs where they grow before moving into the blood stream.

Mechanism of action of mycobacterium tuberculosis infection

In the course of infection, mycobacterium tuberculosis is phagocytized by macrophages and other innate system cells upon entry into the lungs. The receptors involved in uptake M.Tuberculosis can vary and the bacterium has adapted phagocytosis through, for example, the mannose receptor or the CR3 receptor to prevent macrophage activation.  Mycobacterium tuberculosis, while residing in the phagosomes, delays phagosome maturation and fusion with lysosomes. It therefore replicates inside macrophages as their niche within the immune system.

A delayed adaptive immune response can contain the pathogen in granulomas during later stages. One of the immune evasion strategies of Mycobacterium tuberculosis is the deregulation of lipid metabolism, leading to the formation of foamy macrophages, a hallmark of granulation in tuberculosis lesions.

Mycobacterium tuberculosis lipoprotein biosynthesis

Mycobacterium tuberculosis Lipoproteins are a group of selected bacteria proteins characterized by a lipidated N-terminus.

Lipoproteins play major roles in M.Tuberculosis infection. The common features of lipoprotein are the presence of a conserved consensus sequence called Cysteine at position +1. Lipobox directs the processing of the proplipoprotein to form the mature acylated protein. This process is mediated by the consecutive activity of prolipoprotein diacylglyceryl ransferace (Lgt) and lipoprotein signal peptidase (LspA).

In Gram-negative bacteria, the prolipoproteins are translocated across the cytoplasmic membrane via a secA-dependent pathway. After translocation of the preprolipoprotein, the p of the preprolipoprotein, the phosphatidylglycerol:prolipoprotein diacylglyceryl transferase (lgt) transfers a diacylglyceryl moiety from phosphaatylglycerol to the sulph diacylglyceryl transferase (lgt) transfers a diacylglyceryl moiety from phosphaatylglycerol to the sulphydryl group of the prolipoprotein.

Diacylglyceryl modification is a prerequisite for the cleavage of the signal peptide bythe lipoprotein-specific sgnal peptidase (LspA). Lipoproteins are anchored to the cell membrane by the lipidated N-terminus. LspA is essential for growth and viability of Gram-negative bacteria.