Mycobacterium Lecture
Mycobacterium Lecture
Mycobacterium Lecture
• Obligate aerobes
• Acidfast
• Generation time
– 1520 min for E. coli
– 60 min for C. diphtheriae
– 300 min for M. tuberculosis
– Requires ≥ 3 wk to grow from small
inocula
– M. paratuberculosis grows very slowly (up
to 5 months)
• Complex cell wall lipids: mycolic acids
– structural, immunostimulatory, protect
during intracellular growth
Mycobacterium bovis
• Tuberculosis in cattle,
humans, swine, others
• Eradication program in
cattle begun in 1917, now
nearly complete
Mycobacterium leprae
• Tuberculoid leprosy
– little disfigurement
– organisms in wellcontained granulomatous
lesions in tissue
• Lepromatous leprosy
– disfigurement, nodular swellings
– slow fibrosis of peripheral nerves, anesthesia
– shortening of toes and fingers in response to
repeated unfelt trauma; spontaneous
amputations often occur (sloughing)
Mycobacterium avium
• Human disease
– pulmonary, disseminated
infections
• Most common
opportunistic bacterial
infection of AIDS patients
Mycobacterium paratuberculosis
Johne’s disease
Disease Caused by Mycobacterium tuberculosis
• Epidemic in 19th century US, Europe, England
– annual death rate nearly 1% of population
– declined with improved living conditions, therapy, screening,
aggressive case studies
• Mid1980s: increased number of cases
– immigrants: 25% of new TB cases in US
– drug resistance
• TB in AIDS patients
– higher rate in AIDS vs "normal" in developing countries
– ≈ same rate for both in developed countries
– exposure => shedding greatly shortened among
immunocompromised
Pathogenesis
• Normally slowlydeveloping disease, not highly contagious
• Rapid, effective activated Mφ response determines outcome
• Healthy adult, exposure to low numbers
– activated Mφ appear early enough to stop infection
– no appreciable damage to lung, skin test positive
• Poor response, large inoculum, longterm exposure
– grow in Mφ, layer of Mφ, T cells forms
– granuloma (tubercle); calcification
• Symptoms:
– fever, coughing, bloody sputum
– progressive, irreversible lung destruction
• Walledoff lesions may contain live bacteria
– recrudesce following immunosuppression
– reactivation TB
Diagnosis
• TB skin test: key to rapid easy surveillance
– ID injection of tuberculin, PPD
– stimulates preprimed CD4 T helper cells at injection site
– 3 5% becoming pos develop active TB
– decrease in immune competence (AIDS): converts pos to neg
–
Vaccination
Prevention and Therapy
• Vaccination with M. bovis BCG (attenuated)
– given orally, safe, cheap (10 cents per dose)
– enters Mφ, replicates briefly before being killed, elicits
immunity
– questionable efficacy (mixed results in field trials)
• Recent converters take full course of therapy
– streptomycin, isoniazid (INH), rifampin
– high frequency of resistance when used singly, shortened
course (requires two pills, nausea side effect)