CHAPTER 1
INTRODUCTION
1.1 TUBERCULOSIS
Tuberculosis (TB) is an infectious disease caused by the bacillus Mycobacterium tuberculosis. TB is a major global health problem and it ranks alongside Human Immunodeficiency Virus (HIV) as a leading cause of death worldwide. According to the estimates of WHO global tuberculosis report of 2015, there were 9.6 million people who developed TB and 1.5 million who died from the disease in 2014.
1.2 TRANSMISSION AND PATHOGENESIS OF TB
TB infection occurs when a person inhales a droplet containing tubercle bacilli. Typically, these bacteria are engulfed by the macrophages where it is partially inhibited or destroyed. Then a small number of mycobacteria may multiply intracellularly and are released when the macrophages die. This live bacterium may actually transmit the infection by the way of lymphatic channels or through the bloodstream to more distant tissues and organs where TB infection can occur and lead to severe chronic state.
1.3 MYCOBACTERIAL CELL WALL: THE PERMEABILITY BARRIER
The cell wall of mycobacteria is structurally distinct from that of both Gram-positive and Gram-negative bacteria. It is usually composed of long chain fatty acids, such as mycolic acids which are covalently linked to the arabinogalactan-peptidoglycan complex …show more content…
The FAS-I and FAS-II pathways are connected by a key enzyme, namely β-ketoacyl ACP synthase III or FabH, which catalyses the decarboxylative condensation of malonyl-ACP with the acyl-CoA (C16–C20) products of the FAS-I pathway. The resulting 3-ketoacyl-ACP product is reduced to an acyl-ACP and shuffled into the FAS-II cycle. The FAS-II pathway has four enzymes MabA (β-ketoacylreductase), β-hydroxyacyldehydrase, InhA (enoyl reductase) and KasA/B (β-ketoacyl synthase). For each cycle, the growing acyl chain is extended by two carbon units and finally produces long chain fatty acids which are of C50-C58 in
INTRODUCTION
1.1 TUBERCULOSIS
Tuberculosis (TB) is an infectious disease caused by the bacillus Mycobacterium tuberculosis. TB is a major global health problem and it ranks alongside Human Immunodeficiency Virus (HIV) as a leading cause of death worldwide. According to the estimates of WHO global tuberculosis report of 2015, there were 9.6 million people who developed TB and 1.5 million who died from the disease in 2014.
1.2 TRANSMISSION AND PATHOGENESIS OF TB
TB infection occurs when a person inhales a droplet containing tubercle bacilli. Typically, these bacteria are engulfed by the macrophages where it is partially inhibited or destroyed. Then a small number of mycobacteria may multiply intracellularly and are released when the macrophages die. This live bacterium may actually transmit the infection by the way of lymphatic channels or through the bloodstream to more distant tissues and organs where TB infection can occur and lead to severe chronic state.
1.3 MYCOBACTERIAL CELL WALL: THE PERMEABILITY BARRIER
The cell wall of mycobacteria is structurally distinct from that of both Gram-positive and Gram-negative bacteria. It is usually composed of long chain fatty acids, such as mycolic acids which are covalently linked to the arabinogalactan-peptidoglycan complex …show more content…
The FAS-I and FAS-II pathways are connected by a key enzyme, namely β-ketoacyl ACP synthase III or FabH, which catalyses the decarboxylative condensation of malonyl-ACP with the acyl-CoA (C16–C20) products of the FAS-I pathway. The resulting 3-ketoacyl-ACP product is reduced to an acyl-ACP and shuffled into the FAS-II cycle. The FAS-II pathway has four enzymes MabA (β-ketoacylreductase), β-hydroxyacyldehydrase, InhA (enoyl reductase) and KasA/B (β-ketoacyl synthase). For each cycle, the growing acyl chain is extended by two carbon units and finally produces long chain fatty acids which are of C50-C58 in