Wednesday, October 28, 2009

What are mycobacteria?


Definition

Members of the bacterial genus Mycobacterium are widely
distributed in nature. Mycobacteria, which cause noteworthy diseases such as
tuberculosis and leprosy, affect healthy humans,
nonhuman animals, and persons with compromised immune systems.





Natural Habitat and Features

Members of the genus Mycobacterium are widely distributed, rod-shaped bacteria. Many are free-living and are found in soil, water, and marshes and in association with various animal species; a few can live only in or on animals. In culture, mycobacteria cells can vary from spherical (cocci) to ovoid (coccobacilli) to rods (bacilli) to branched rods to long cordlike rods. They are nonmotile, with the exception of marinum.


When grown on artificial media, mycobacteria form flat, dry, scaly colonies. Some Mycobacterium spp. are pigmented. Photochromogens, such as kansasii, marinum, and simae, form pigmented colonies only when grown in the light. Scotochomogens, such as scrofulaceum, gordonae, and szulgai, form yellow to orange colonies when grown in the dark or in the light. Tuberculosis, bovis, ulcerans, and fortuitum nonchromogens produce dull-colored colonies that are white or cream-colored, pale yellow, or tan if grown in the light or in the dark.



The growth rates of mycobacteria differ wildly. Those mycobacteria that can form colonies within seven days are classified as rapid growing, and those that require more time to form colonies are called slow growing.


All members of the genus Mycobacterium are surrounded by a rather thick cell wall that is waxy. Bacteria typically contain a cell wall composed of a polymer called peptidoglycan, but mycobacteria have a modified peptidoglycan layer that is cross-linked to polysaccharides called arabinogalactans and unusual lipids known as mycolic acids. These mycolic acids form a waxy layer outside the peptidoglycan layer with a poorly characterized outer lipid layer. Mycobacteria do not stain when subjected to a Gram’s stain, but are, instead, successfully stained by an acid-fast stain that uses carbolfuschin, which stains members of the Mycobacterium red.


Mycobacteria were formerly identified by biochemical tests, but methods of
identification, now more rapid, include the separation of cell-wall mycolic acids,
in which mycolic acids from mycobacterial cell walls are separated by high
performance liquid chromatography and compared with a database of known standards
to identify specific Mycobacterium spp. Another way to identify
members is through nucleic acid sequencing, which uses gene sequencing systems to
sequence the 16S ribosomal ribonucleic acid (RNA) genes and compare them with
published sequences to rapidly identify mycobacterial isolates.




Pathogenicity and Clinical Significance

The most clinically significant disease caused by mycobacteria is tuberculosis.
Tuberculosis causes the vast majority of tuberculosis cases,
but members of the tuberculosis complex, which include
bovis, africanum, canetti,
caprae, and microti, can also cause
tuberculosis, or tuberculosis-like diseases, especially in persons whose immune
systems are compromised.


When tuberculosis-causing mycobacteria are inhaled, they settle deep within the lungs and are engulfed by a lung-based white blood cell called an alveolar macrophage. The organisms can survive and divide within the macrophages. Other uninfected macrophages surround the infected cell, fuse, and then engulf the cell to deprive the bacterial cells of oxygen. This type of response is called a granuloma, which produces a bump or tubercle in the lung. These tubercles can last the remainder of a person’s life; they constitute pulmonary tuberculosis.


Many cases of pulmonary tuberculosis cause no visible symptoms, and so are
asymptomatic, but one system that does commonly appear is a cough. Additional
symptoms include trouble breathing (dyspnea) and coughing up blood
(hemoptysis). Chest X rays show middle and lower lung
infiltrates. The tuberculin skin test is the most reliable way to diagnose
tuberculosis.


If the infected person becomes weakened, these tubercles can break open, and the mycobacterial cells can disseminate to any organ of the body. This represents disseminated or extrapulmonary tuberculosis. The main sites of dissemination are the lymphatic system and the pleural membranes of the lungs, but the organism can spread to other organs as well. The wasting caused by disseminated tuberculosis is popularly known as consumption.


Leprosy (Hansen’s disease), a chronic, progressive disease that can permanently damage the nerves, skin, eyes, and limbs, is caused by leprae and lepromatosis. This disease results from granulomas of the peripheral nerves and mucosae of the upper respiratory tract. The primary external sign of this disease is a skin lesion.


Nontuberculous mycobacteria (NTM) or environmental or atypical mycobacteria,
cause neither tuberculosis nor leprosy. NTM cause lung diseases, lymph node
infections (lymphadenitis), skin and soft tissue infections, and
disseminated disease in persons with acquired immunodeficiency syndrome
(AIDS).




Drug Susceptibility

Combination drug treatments are the rule when treating mycobacterial
infections. Because mycobacteria are resistant to
antibiotics typically used to treat bacterial
infections, separate groups of antibiotics have been designed
especially for these infections.


First-line treatment for pulmonary tuberculosis consists of daily isoniazid,
rifampin, ethambutol, and pyrazinamide for two months followed by four months of
isoniazid and rifampin three times per week. Alternative treatment regimes exist,
and if first-line drugs do not work or are not tolerated, available second-line
drugs include cycloserine, ethionamide, fluoroquinolones (levofloxacin,
moxifloxacin, and gatifloxacin), p-aminosalicyclic acid, aminoglycosides
(streptomycin, kanamycin, and amikacin), and capreomycin.


Treatment of extrapulmonary tuberculosis extends the second phase of treatment for seven months, but treatment of tuberculosis of the central nervous system extends the second phase of treatment for ten months. Steroid drugs are also given to reduce the swelling and inflammation associated with extrapulmonary tuberculosis.


Mycobacteria that are resistant to isoniazid and rifampicin are termed multi-drug-resistant (MDR). Those mycobacteria that are resistant to isoniazid, rifampin, fluoroquinolone, kanamycin, capreomycin, or amikacin are designated as extensively drug-resistant (XDR). To treat MDR- or XDR-tuberculosis, the infecting Mycobacterium is isolated from the infected person and are laboratory tested for drug sensitivities, after which the infected person is given a combination of five drugs, against which the infecting Mycobacterium is sensitive for at least eighteen months.


Leprosy is treated with a combination of rifampin, dapsone (a sulfa drug),
and clofazimine for twelve months. NTM infections require a combination of
macrolides, ethambutol, and rifamycin for up to one year.




Bibliography


Dormandy, Thomas. The White Death: A History of Tuberculosis. London: Hambledon & London, 2001. A pathologist traces the impression left by tuberculosis on human history, examines the suffering the disease has caused, and discusses how Western countries mitigated its effects.



Gandy, Matthew, and Alimuddin Zumia, eds. The Return of the White Plague: Global Poverty and the “New” Tuberculosis. New York: Verso, 2003. An engrossing analysis of the social and economic impacts of multi-drug-resistant tuberculosis.



Hopewell, Philip C., and Robert M. Jasmer. “Overview of Clinical Tuberculosis.” In Tuberculosis and the Tubercle Bacillus, edited by Steward T. Cole et al. Washington, D.C.: ASM Press, 2005. A clear and magisterial treatment of the clinical features of tuberculosis.



LaBombardi, Vincent J. “The Genus Mycobacteria.” In Practical Handbook of Microbiology, edited by Emanuel Goldman and Lorrence H. Green. 2d ed. Boca Raton, Fla.: CRC Press, 2009. A brief, informative summary of the clinical aspects of the genus Mycobacterium in a standard medical microbiology reference book.



Madigan, Michael T., and John M. Martinko. Brock Biology of Microorganisms. 12th ed. Upper Saddle River, N.J.: Pearson/Prentice Hall, 2010. This text outlines many common bacteria and describes their natural history, pathogenicity, and other characteristics.

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