Abstract
The cell wall of Mycobacterium tuberculosis is made up of mycolic acids which are found to play important role in pathogenesity by modification of double bonds at specific sites on mycolic acid precursors by the action of cyclopropane mycolic acid synthases (CMASs) that belong to a family of S-adenosyl-methionine-dependent methyl transferases. PcaA is an cyclopropane mycolic acid synthase required for cording, persistence and virulence of Mycobacterium tuberculosis and modifies mycolic acid by cyclopropanation of proximal double bond to cis cyclopropane generating alpha mycolic acid. A molecular docking of selected compounds was performed and the differences in their binding modes were investigated in order to design novel lead compound that can act as better antitubercular agent targeting cyclopropane mycolic acid synthases.
Highlights
Mycobacterium tuberculosis (Mtb) is an obligate human pathogen that causes tuberculosis (TB) and predominantly grows in the host phagocytes
Establishment of an all-around close apposition between the phagosome membrane and the mycobacterial surface known as phagosome maturation block (PMB) will occur only when phagosomes contain a single mycobacterium [3]
When a phagosome contains more than one mycobacterium or mycobacterial clumps, PMB is not achieved leading to phagosome maturation and fusion with lysosomes [2, 3]
Summary
Mycobacterium tuberculosis (Mtb) is an obligate human pathogen that causes tuberculosis (TB) and predominantly grows in the host phagocytes. The bacilli remain in a weakly acidic and noncytolytic environment by residing in the phagosomes of phagocytes and prevent the maturation and fusion of phagosomes with lysosomes [1,2]. Establishment of an all-around close apposition between the phagosome membrane and the mycobacterial surface known as phagosome maturation block (PMB) will occur only when phagosomes contain a single mycobacterium (loner phagosomes) [3]. When a phagosome contains more than one mycobacterium or mycobacterial clumps (social phagosome), PMB is not achieved leading to phagosome maturation and fusion with lysosomes [2, 3]. PMB is a strategy for altering the host immune response and there by sequestering pathogenic mycobacteria away from antigen presenting compartments [4]. Mycobacteria have an unusual cell wall whose outer layer is composed of mycolic acids which are very long-chain branched fatty acids that are either covalently attached to the cell wall or in the form of trehalose dimycolate (TDM), a toxic glycolipid of M. tuberculosis (Figure 1) [5]
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