Mycobacterium tuberculosis persistently affects approximately two billion people worldwide. The proliferation of Mtb relies on its mechanism to resist stress from nitric oxide and other reactive nitrogen intermediates generated from the immune system response. The bacteria primarily takes up residence within the macrophages of the mammalian cell where the environment has a low pH and is also subject to nitrosaltive and oxidative stress. The nature of oxidative stress originates from the reaction of NO with superoxide from common bacterial metabolism to generate peroxynitrate.
The term pathogenicity embodies the quality of a whole microbial species comprising several strains of varying virulence- that is
Only rarely is infectious disease the direct and invariable consequence of an encounter between host and pathogen. Rather, it is the eventual outcome of complex interactions between them. Most intracellular bacteria, however enter the host through the mucosa and bacterial entry is frequently initiated by adhesion to cells of the epithelial mucosa. Major ports of entry are the lungs for airborne pathogens, like Mtb, this bacteria pass through the epithelial layers. Either they actively induce transcytosis through the epithelial cells, or they are passively translocated within macrophages. Bacteria may removed by nonspecific defense mechanisms such as mucociliary movements and gut peristalsis. Bacteria survive these nonspecific defense reaction colonize deeper into the tissue and stably infect a suitable niche. At this stage, the host body will pay sufficient attention to the infectious agent, as indicated by the development of specific immune response.
Mtb- this paradigm intraceillular bacterium is an acid-fast bacillus, due to its myoacid reside in its cell wall. It can replicate itself within approximately in 12 hours. Tubercle bacilli are obligate aerobes and hence prefer tissue sites with high present from oxygen level, such as lung. M tuberculosis, as well as other mycobacteria, contain abundant lipids, glycolipids, and waxes, which are responsible not only for the hydrophobic character of the mycobacteria, but also for their acid-fastness, strong adjuvanticity, resistance against complement lysis, and resistance against acids, alkaline, and simple disinfectants. Most recent findings have revealed that certain mycobacterial lipids and lipoglycan serve as antigenic targets for a small population of unconventional T cells in humans. Mtb cause tuberculosis, which is of paramount medical importance globally. The disease is characterized by long incubation time, dormant infection, and protracted course of disease. It is estimated that, globally, 60 million people suffer from tuberculosis and that every year 8 million new cases arise. Annually, 3 million people die of this disease, making Mtb the major killer among all infectious agents. Infected individuals harbor Mtb inside small granulomas at sequestered tissue sites. Persistence of Mtb in these seclusion does not remain unrecognized by the immune system; rather, it is controlled by T cell. Hence, the vast majority of infected people remain healthy, only a minority develop disease following weakening of the immune response. Primary infection generally proceeds via the aerosol route, and the lung remains the principal site can be infected following reactivation of dormant foci and hematogenic-lymphogenic dissemination.
Antibody-coated Mtb lose their capacity to block discharge of lysosomal enzyme, suggesting an auxiliary function of antibodies in cell-mediated protection against tuberculosis. Finally, the robust, lipid-rich wall of mycobacteria renders them highly resistant against enzymatic attack.
Mtb can also conduct process of acidification aroung its surrounding through its proton pump and NH4+ production.
This organism causes tuberculosis. Worldwide, Mt causes more deaths than any other single microbial agent. About one third of the world’s population is infected with this organism. Each year, it is estimated that 3 million people die of tuberculosis and that 8 million new cases occur.
Mt grows slowly due to synthesis of Myolic acid. Because growth is so slow, cultures of clinical specimens must be held for 6-8 weeks before being recorded as negative. Mt requires complex nutrients and dyes. Mt is an obligate aerobes, this explain its predilection for causing disease in highly oxygenated tissues such as the upper lobe of the lung and the kidney. Its cell wall contains several complex lipid; a long chain fatty acids called Mycolic acids, which contribute to the organism’s acid-fastness; wax-D, one of active components that help to enhance the immune response to many; and phosphatides, which play a role in caseation necrosis.
Mt is relatively resistant to acids and alkalis. NaOH is used to concentrate clinical specimens; it destroys unwanted bacteria, human cells, and mucus but not the organism. Mt is resistant to dehydration and so survives in dried expectorated sputum; this property may be important in its transmission by aerosol.
Stains of Mt resistance to the main antimycobacterial drug, isoniazid, as well as strains resistant to multiple antibiotics (MDR), have become a worldwide problem. This resistance is attributed to one or more chromosomal mutations, because no plasmids have been found in this organism. One of these mutations is in a gene for Mycolic acid synthesis, and another is in a gene for catalase-peroxidase, an enzyme required to activate isoniazid within the bacterium.
Mt is transmitted from person to person by respiratory aerosol, and its initial site of infection is of infection site of infection is the lung. In the body, it resides chiefly within macrophages. Humans are the natural reservoir of Mt; there is no animal reservoir. Most transmission occurs by aerosols generated by the coughing of “smear-positive” people. In the US, tuberculosis is almost exclusively a human disease. In developing countries, M bovis also causes tuberculosis in humans. The disease tuberculosis occurs in only a small number of infected individuals. In the US, most cases of tuberculosis are associated with reactivation in elderly, malnourished men. The factors, rather than genetic ones, probably account for the high rate of infection among Native Americans and Blacks.
Mt produces no extoxins and does not contain endotoxin in its cell wall. In fact, no mycobacteria produce toxins. Mt survives and multiplies within a cellular vacuole called a phagosome. The organism produces a protein called “exported repetitive protein” that prevents the phagosome from fusing with the lysosome, thereby allowing the organism to escape the degradative enzymes in the lysosome.
Lesions are dependent on the presence of the organism and the host response. There are two types of lesions. One is exudative lesion, which consist of an acute inflammatory response and occur chiefly in the lungs at the initial site of infection. Second lesion is the granulomatous lesion, which consist of a central area of giant cells containing tubercle bacilli surrounded by a zone of epithelioid cells. A tubercle is a granuloma surrounded by fibrous tissue that has undergone central caseation necrosis. Tubercles heal by fibrosis and calcification. The primary lesion of tuberculosis usually occurs in the lungs. The parenchymal exudative lesion and the draining lymph nodes together are called a Ghon complex. Primary lesions usually occur in the lower lobes, whereas a reactivation lesion usually occurs in the apices. Reactivation lesions also occur in other will-oxygenated sites such as the kidneys, brain, and bone. Reactivation is seen primarily in immunocompromised or debilitated patients.
Spread of the organism within the body occurs by two mechanisms; one is a tubercle can erode into a brochus, empty its caseous contents, and thereby spread the organism to other parts of the lungs, to the gastrointestinal tract if swallowed, and to other persons if expectorated. Second mechanism is by disseminate via the bloodstream to many internal organs. Dissemination can occur at an early stage if cell-mediated immunity fails to contain the initial infection or at a late stage if a person becomes immunocompromised.
Treatment & Resistance-
Multiple-drug therapy is used to prevent the emergence of drug-resistant mutants during the long duration of treatment. Isoniazid, a bactericidal drug, is the mainstay of treatment. Treatment for most patients with pulmonary tuberculosis is with three drugs: INH, rifampin and pyrazinamide. INH and rifampin are given for 6 months, but pyrazinamide treatment is stopped after 2 months. In patients who are immunocompromised , or who are likely to have INH- resistant organisms a fourth drug, ethambutol, is added and all four drug are given for 9-12 months. Although therapy is usually given for months, the patient’s sputum becomes noninfectious within 2-3 weeks. The necessity for protracted therapy is attributed to the intracellular location of the organism, caseous material, which blocks penetration by the drugs and the slow growth of the organism. AIDS primary target for MDR.
The incidence of tuberculosis began to decrease markedly even before the advent of drug therapy in the 1940s. This is attributed to better housing and nutrition, which have improved host resistance. At present, prevention of the spread of the organism depends largely on the prompt identification and adequate treatment of patients who are coughing up the organism. The use of masks and other respiratory isolation procedures to prevent spread to medical personnel is also important.
A vaccine containing a strain of live, attenuated M bovis can be used to induce partial resistance to tuberculosis. The vaccine is effective in preventing the appearance of tuberculosis as a clinical disease, especially in children, although it does not prevent infection by Mt. It is used in the US because reaction can appear in the tuberculin skin test that can confuse its interpretation and because the incidence of the disease is low enough that is not cost-effective.
Pasteurization of milk and destruction of infected cattle are important in preventing intestinal tuberculosis.
BCG vaccine is also used as nonspecifically stimulate cell-mediated immunity, which can inhibit the growth of the carcinoma cells.
Clinical findings are protean; many organs can be involved. Fever, fatigue, night sweats, and weight loss are common. Pulmonary tuberculosis causes cough and hemoptysis.
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