The Mycobacterium tuberculosis oriC (the origin of chromosomal replication) region contains 13 non-perfect DnaA boxes. The M. tuberculosis initiator protein, DnaA, was overexpressed in Escherichia coli as a soluble His-tagged fusion protein. The purified protein His6MtDnaA was investigated for its binding properties to DnaA boxes from the oriC region. Gel retardation demonstrated that the DnaA from M. tuberculosis requires two DnaA boxes for efficient binding. Electron microscopy as well as DNase I footprinting showed that the His6MtDnaA protein binds to four specific regions, which correspond to the location of 11 out of 13 previously identified DnaA boxes within the M. tuberculosis oriC. Probably, in M. tuberculosis, DnaA molecules by co-operative binding of numerous ‘non-perfect’ DnaA boxes assemble along the oriC region and subsequently form a massive nucleoprotein complex.
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Tuberculosis is probably one of the greatest killers of all time, over the centuries taking more than 1 billion lives and up to 2 million people every year (i.e., one life every 15 seconds, as opposed to a life lost in an accident every 50 seconds). Every year, TB infects up to 100 million people worldwide, and up to 8 million develop active disease. If the tuberculosis is not treated, every source case infects, on average, 10 to 15 other persons each year. TB can be considered a social disease, disrupting families emotionally, educationally, and economically. Furthermore, only about 20% of worldwide TB cases are detected and treated successfully.
Pulmonary tuberculosis is one of the major cases of blood in sputum; however, it is uncommon (Ravaglione et al, 1995, p. 224). Other chest complaints, such as shortness of breath or pain, are unusual. On examination, listening to the lungs may disclose rales or crackles and signs of pleural effusion (the escape of fluid into the lungs).
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Tuberculosis is spread from person to person through airborne droplets, when a person that is infected with TB coughs, sneezes, talks, and/or sings the TB germs is released into the air. Only a few germs are needed to be infected. The person must be in the same area an affected individual is in and inhale the droplets to be affected. Once the bacillus is inhaled into the lungs, the bacilli start to multiply causing lung inflammation also known as nonspecific pneumonitis. To cause an immune reaction the bacilli will travel through lymphatic system and become lodged in the lymph nodes. Lung inflammation causes the activation of the alveolar macrophages and neutrophils. Granulomas, new tissue masses of live and dead bacilli, are surrounded by macrophages, which form a protective wall. They then transform into a fibrous tissue mass, the central portion is called a ghon tubercle. The bacterial then necrotic, forming a cheesy mass, this mass may become calcified and form a collagenous scar. At this point, the bacteria become dormant and there is no further progression of the active disease. The disease can become active again by re-infection or activation of the dormant bacteria.
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During the middle of World War II, the greatest development towards the elimination of tuberculosis was developed. This treatment was known as chemotherapy. Streptomycin was the drug initially used in this treatment and was very effective. However, soon after doctors began administering Streptomycin strands of drug resistant TB began to appear. New drugs rapidly began to be developed which when used in conjunction could prevent the development of drug resistant tuberculosis. Following streptomycin, p-aminosalicylic acid (1949), isoniazid (1952), pyrazinamide (1954), cycloserine (1955), ethambutol (1962) and rifampin (rifampicin; 1963) were introduced as anti-TB agents. Aminoglycosides such as capreomycin, viomycin, kanamycin and amikacin, and the newer quinolones (e.g. ofloxacin and ciprofloxacin) are only used in drug resistance situations. Exposed to a single effective anti-TB medication, the predominant bacilli, sensitive to that drug, are killed; the few drug resistant mutants, likely to be present if the bacterial population is large, will, multiply freely. Since it is very unlikely that a single bacillus will spontaneously mutate to resistance to more than one drug, giving multiple effective drugs simultaneously will inhibit the multiplication of these resistant mutants. This is why it is absolutely essential to treat TB patients with the recommended four drug regimen of isoniazid, rifampin, pyrazinamide and ethambutol or streptomycin.
It is essential that the World Health Organization continue to educate the public of all nations on the most current treatments of tuberculosis to prevent the impending spread of drug resistant tuberculosis throughout the world.
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...S. and that 26 percent of these were co-infected with HIV. The progression of tuberculosis varies greatly among people (1:887). It progresses more rapidly in blacks and Native Americans than in whites. The rate of progression depends mainly on the strength of the person's immune system. Active tuberculosis usually begins in the lungs (pulmonary tuberculosis). Tuberculosis that affects other parts of the body (extrapulmonary tuberculosis) usually comes from pulmonary tuberculosis that has spread throughout the bloodstream. Clinical Presentation: The first symptoms of tuberculosis are usually a cough and a feeling of not being well (1:887). The cough may produce a small amount of green or yellow sputum in the morning, which usually increases as the disease progresses. Eventually the sputum may be streaked with blood. One of the most common symptoms is awakening in the night drenched with a cold sweat caused by the subsiding of a low-grade fever. Shortness of breath may signal the presence of air (pneumothorax) or fluid (pleural effusion) in the pleural space. About 95 percent of pleural effusions in young adults are caused by a recent infection with Mycobacterium tuberculosis and need to be recognized as such so that they do not progress to full-blown tuberculosis (1:888). In a new infection, the bacteria travel from the lesion in the lung to the draining lymph nodes. The infection may spread to a joint, causing tuberculous arthritis. The most commonly affected...