BSCI 424 — PATHOGENIC MICROBIOLOGY — Fall 2000

Mycobacterium Summary


Mycobacterium tuberculosis:

  CMN group: Corynebacterium, Mycobacterium, Nocardia are grouped together on the basis of distinguishing factors that include complex cell wall components, presence and type of mycolic acids, adjuvant activity, presence of cord factor, sulfolipids, iron-chelating compounds, polyphosphate, and serological cross-reactivity.

  Very slow growing

  Prototrophic (ability to build all required components from basic carbon and nitrogen sources) with glucose (carbon source) and ammonium ion (NH4+)(nitrogen source) or glycerol and asparagine

  Many specific mycobacteriophages

  Acid-fast bacilli (see WebLinked image; see WebLinked image; see WebLinked image); red on blue background with Ziehl-Nielsen acid-fast stain

  Non-spore former, resistant to drying, sunlight, and chemical disinfectants, particularly in sputum

  Obligate aerobe, but facultative intracellular pathogen with two clinical forms:

    1. Pulmonary disease
    2. Extra-pulmonary disseminated disease

  Many immunoreactive substances. Important antigens include: purified protein derivative (PPD), cord factor, and old tuberculin (OT).

  Correlation of strain virulence with cord factor, but specific determinants of pathogenicity have not been identified.

  Tuberculosis is leading cause of reportable infectious diseases; 8-10 million new cases and 3 million deaths every year.

  Single most critical factor in tuberculosis infection is the severity of infectiousness of the source case

  Organisms transmitted from infectious cases via droplet nuclei suspended in the air. Aerosols produced by talkin, coughing, sneezing, breathing dry to droplet nuclei (1-10 um diameter) that are inhaled deep into the alveoli of the lungs.

  Factors that influence risk of contracting tuberculosis disease, i.e., progressing from infection to disease include: age, sex, race, personal habits, co-existing disease, and socioeconomic status

  Treatment with Isoniazid (INH) or rifampin and second line drugs or attempted preventive therapy with INH and BCG prophylaxis

  Primary pulmonary infection with secondary infection of pulmonary or extra-pulmonary sites

  Tissue destruction and fibrosis (fibrous walling off of lesions, i.e. granulomatous reaction) caused by host response to infection.

  Initially, a the host mounts a non-specific inflammatory response: organisms are phagocytosed by alveolar macrophages, inhibition of phagolysosome fusion, intracellular multiplication, and spread to regional lymph nodes, then the blood stream and seeded throughout the body. Secondary infection is either in a pulmonary site, from ongoing multiplication of organisms seeded to apices of the lungs or in any extrapulmonary site.

  Two to four weeks after infection, cell-mediated immunity and tuberculin hypersensitivity develops.

  Cytokines derived from T-cells activate the macrophages and render them capable of killing the bacteria. A small antigenic burden (limited number of infecting cells) results in destruction of the bacilli and minimal tissue necrosis. With a large antigenic burden (large number of bacilli), this cellular immune response results in tissue necrosis.

  The hypersensitivity response to tuberculin results in localized collections of cytokine-activated macrophages (granulomas) prevent further spread of the organisms. Larger, necrotic or walled-off granulomas become surrounded by fibrin (tubercle formation) which effectively protects the organisms from macrophage killing. Bacilli remain dormant (quiescent) in this stage for years or decades. When immunological response wanes, bacilli can reactivate.

  Secondary or reinfection tuberculosis resulting from reactivation of quiescent foci of bacilli; occurs in small number of infected persons despite acquired cellular immunity. Lesions remain localized because of cell-mediated immunity Hypersensitivity promotes fibrotic walling-off of foci (characteristic tubercle granuloma).

  Koch demonstrated Kochís postulates with M. tuberculosis, but noone has yet been able to satisfy his postulates with this pathogenís sister species M. leprae. M. leprae has never been cultured in vitro.

 

Mycobacterium bovis:

  Formerly important cause of bovine tuberculosis transmitted by ingestion of contaminated milk. Is uncommon in the United States, since the advent of pasteurization and herd surveillance.

  Now important as species from which attenuated strain (M. bovis, Bacillus of Calmette and Guerin (BCG)) is used for preparation of tuberculosis BCG vaccine (see WebLinked image)

 

Mycobacterium avium-intracellulare :

(see WebLinked image)

 

Mycobacterium leprae:

  CMN group: Corynebacterium, Mycobacterium, Nocardia are grouped together on the basis of distinguishing factors that include cell wall components, presence and type of mycolic acids, adjuvant activity, presence of cord factor, sulfolipids, iron-chelating compounds, polyphosphate, and serological cross-reactivity.

  Hansenís disease, Hansen described bacilli in lepromatous skin lesions

  Very slow growing, acid-fast bacilli (see WebLinked image; see WebLinked image)

  Chronic, obligate intracellular pathogen; humans are only natural host

  Acquired by direct contact with persons shedding large numbers of bacilli in lepromatous ulcer exudates or nasal secretions. Major portal of entry is respiratory tract

  Never cultured in vitro ; only cultured in mouse foot pads and nine-banded armadillos

  12 million infected; Geographic, ethnic, and socioeconomic factors contribute to spread of leprosy

  Spectrum of disease types from relatively benign tuberculoid form (stable) through a series of unstable intermediate forms to the most severe lepromatous form (stable) are reflective of the patientís immune response to the bacilli

  In tuberculoid leprosy, lymphocytes and mature granulomas in skin, organisms invade Schwann cells of nerves and few can be cultured; strong delayed hypersensitivity reaction but a weak humoral antibody response relatively few cells because cell-mediated immune production of cytokines activates killer macrophages.

  In lepromatous leprosy, strong humoral antibody response, but defective cellular response to M. leprae antigens; histiocyte involvement with massive numbers of bacilli within dermal macrophages (109 per gram of skin tissue) and Schwann cells (nerve involvement less than tuberculoid form); organisms invade vascular channels with continuous bacteremia; bilateral lesions and folding of skin, especially of the face into a lion-like appearance

  Leprosy is a disease of low infectivity that is most likely associated with a defective cell-mediated immune response

  For a minimum of two years to life, treatment is:

    1. Dapsone (DDS) , rifampin, and clofazimine with lepromatous leprosy
    2. Dapsone & rifampin with tuberculoid leprosy

  Koch demonstrated Kochís postulates with M. tuberculosis, but noone has yet been able to satisfy his postulates with this pathogenís sister species M. leprae. M. leprae has never been cultured in vitro

 
 

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