MMI 301: Lecture 26: Mycobacterium tuberculosis

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MMI 301: Lecture 26: Mycobacterium tuberculosis
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2013-12-03 18:21:51
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  1. Mycobacterium tuberculosis Dogma
    • Humans are reservoir: 1/3rd world is infected
    • Majority of infected do not show disease, only those that manifest active TB can spread it
  2. Mycobacterium species
    • Animal pathogens:
    • avium, bovis, marinum, avium sp. Paratuberculosis
    • Human pathogens:
    • avium (opportunist in AIDS), leprae, tuberculosis, bovis
  3. Mycobacterium evolution
    • Distinct from both Gram +/-
    • Kinda closer to +
  4. Mycobacterium outer membrane
    • Weird
    • Mycobacterial outer membrane (MOM)
    • Area between MOM and CM contains layers of arabinogalactan-peptidoglycan polymer
  5. How to identify Mycobacterium
    Acid-fast staining
  6. Mycobacterium show what characteristic in morphology
    Roping/Serpentine cords bacilli
  7. Mycobacterium tuberculosis basic biology
    • Unique/Waxy cell wall
    • Slow growing (Month+ for colony)
    • Can be cultured in vitro under high containment
    • Can be studied in animals
  8. Mycobacterium tuberculosis pathology
    • 3 Stages:
    • -Infection: Mtb are actively replicating, symptoms of respiratory illness
    • -Latency/Chronic Phase: Mtb are very low in number, no symptoms, not contagious
    • -Reactivation/Active phase: Mtb increase in number, host immune response causes symptoms

    • Signs of active TB: coughing, tiredness, fever, chest pain, coughing blood, weight loss
    • Detection: skin test, lung x-ray, culturing, sputum smears, blood test.
  9. How does Mycobacterium tuberculosis live intracellularly
    • Mtb prevents phagosome maturation, fusion with lysosome
    • Granuloma formation
  10. How does Mycobacterium tuberculosis stimulate granuloma formation
    • Type VII secretion system (ESX-1)
    • (deleted in BCG strain used for vaccine)
  11. Virulence factors of Mycobacterium tuberculosis
    • No known toxins
    • -Symptoms fully from host response
    • Factors that stop phagosome maturation
    • -Cell wall components (lipoarabinomannin-LAM)
    • -Secreted proteins (Type VII secretion system, PknG kinase)
    • Survive in phagosome thanks to iron acquisition (mycobactins/exochelins)
  12. Mycobacterium tuberculosis test
    • Skin test, measures hypersenstivity to protein derivatives of Mtb injected intradermally¬†
    • If induration (swelling bump) or erythema occur is posistive indicates INFECTION at some point
    • False positive for anyone immunized
    • AIDs give false negatives (probably extends to any immunocomprimised)
  13. Mycobacterium tuberculosis Treatment
    • FIRST LINE:
    • -Isoniazid (INH)-inhibits mycolic acid synthesis)
    • -Ethambutol (inhibits arabinogalactan synthesis)
    • -Pyranzinamide (inhibits fatty acid synthesis)
    • -Rifampicin (inhibits RNA polymerase)
    • Use ALL for 2 mo. INH+Rif for 4 mo. Never Use Separately!
    • SECOND LINE:
    • Ciprofloxacin or Moxiflocaxin
    • MDR/XDR strains
  14. BCG strain
    • Attenuated live strain (Lack T2SS)
    • Cannot be given to AIDS patients
    • Still very much in development
  15. Mycobacterium leprae
    • Causes leprosy
    • Less studied:
    • -less prevelant, cant be grown in culture, Slowest-known growing bacteria, Sequenced
    • Spread person to person via nasal
    • Skin lesions/disfiguring
    • Incubation from 3 weeks to 30 years
  16. Where does research M. leprae come from
    Armidillos (Cannot be grown at all)
  17. Forms of Leprosy
    • Tuberculoid (paucibacillary):
    • -Strong cell immune response, weak humoral antibody response
    • -Many host response cells, few bacteria
    • -Nerve thickening, defined plaque
    • Lepromatous leprosy (multibacillary):
    • -Strong antibody response, low cellular response
    • -High numbers of bacteria
    • -Patchy plaques, extensive tissue destruction
  18. Paratuberculosis
    • M. paratuberculosis causes chronic wasting disease in cattle (Johne's disease)
    • Association between M. paraTB and Crohn's disease
    • Koch's postulates NOT fulfilled
    • Does ParaTB cause Crohn's?

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