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MYCOBACTERIA CORYNEBACTERIA Lecture 40
Faculty: Dr. Alvin Fox
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KEYWORDS Acid Fast Tuberculosis (TB) M. tuberculosis (MDR, XDR)
M. avium - M. intracellulare complex M. bovis M. leprae Tubercle PPD Tuberculin Mycobactin Cord factor BCG Leprosy (Hansen's Disease) AIDS and TB Runyon groups Mycolic acids Diphtheria C. diphtheriae Loeffler's agar Tellurite agar Metachromatic bodies Diphtheria toxin Schick test Diphtheroids
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Mycobacterium tuberculosis
obligate aerobe acid-fast rods
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Tuberculosis (TB, consumption) M. tuberculosis major human disease
healthy people problems association with AIDS multiple drug-resistance
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M. avium- M. intracellulare complex (M. avium)
non-AIDS infection almost never AIDS major bacterial opportunist multiple drug-resistance
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M. bovis spread from cattle infected cattle are culled positive skin test rarely seen in US
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M. leprae leprosy major disease of third world rare in US
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Transmission -tuberculosis
M. tuberculosis causes disease healthy individuals transmitted man-man airborne droplets
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Pathogenesis of tuberculosis
infects lung distributed within macrophages facultative intracellular pathogen inhibits phagosome-lysosome fusion
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Cell-mediated immunity -tuberculosis
infiltration macrophages lymphocytes granulomas tubercules
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Laboratory diagnosis - tuberculosis
skin testing delayed hypersensitivity tuberculin protein purified derivative, PPD X-ray
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Positive skin test -tuberculosis
indicates exposure to organism does not indicate active disease
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tuberculosis Other minor pathogenesis factors mycobactin siderophore
cord factor damages mitochondria
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Laboratory diagnosis M. tuberculosis
acid fast bacteria sputum
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Laboratory diagnosis M. tuberculosis (culture)
grows very slowly two weeks or longer non-pigmented colonies niacin production differentiates from other mycobacteria
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Tuberculosis polymerase chain amplification rapid diagnosis
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Antibotic treatment - tuberculosis
extensive time periods (e.g. 9 months) organism grows slowly, or dormant two or more antibiotics e.g. rifampin and isoniazid resistance minimized
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Tuberculosis and Drug resistance
Multiple drug resistant (MDR) resistant to first line drugs Extremely drug resistant (XDR) Resistant to some of the second line drugs Nearly un-treatable
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Vaccination BCG vaccine an attenuated strain of M. bovis not effective
in US, incidence is low vaccination not practiced immunization interferes with diagnosis
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Mycobacterium leprae
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Leprosy (Hansen's Disease)
M. leprae causative agent chronic disease disfigurement rarely seen in the U.S. common in third world - effective antibiotic therapy recently initiated, incidence way down infects the skin low temperature
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ulcers, resorption of bone
worsened from careless use of hands (nerve damage)
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Leprosy tuberculoid few organisms active cell-mediated immunity
lepromatous many organisms immunosuppression
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Production of M. leprae antigens and
pathogenesis studies in vitro unculturable in vivo growth low temperature armadillo (laboratory and native [e.g. TX]) mouse footpad
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Leprosy lepromin skin testing acid-fast stains skin biopsies
clinical picture
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Other mycobacterial species (including M. avium)
infect immunocompromised host not transmitted man-man, healthy people M. avium – common Other species - rare
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Mycobacterial diseases
tuberculosis-like leprosy-like
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M. avium is much less virulent than M. tuberculosis
Mycobacteria and AIDS M. avium is much less virulent than M. tuberculosis does not infect healthy people infects AIDS patients M. avium infects when CD4 (helper T cell) count greatly decreased M. tuberculosis infection infects healthy people earlier stage of disease more systemic
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Clinical features with AIDS
systemic disease (versus pulmonary) greater in AIDS lesions often lepromatous
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Antibiotic therapy selected primarily for M. tuberculosis if M. avium involved other antibiotics included
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Other species pigmented or not pigmentation in the light in the dark
growth fast slow
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Mycobacterial species identification
cellular fatty acid profiles mycolic acid profiles genetic markers
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Mycolic acids mycobacteria longest chain length strongly acid fast
nocardia intermediate chain length weakly acid fast corynebacteria shortest chain length not acid fast
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Corynebacterium diphtheriae
Gram positive strict aerobe pleomorphic (e.g. club-shaped)
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Diphtheria member of normal flora of pharynx
overgrowth upper respiratory tract pseudomembrane chocking bacteria do not spread systemically The toxin does disseminates .
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This child has diphtheria resulting in a thick gray
coating over back of throat. This coating can eventually expand down through airway and, if not treated, the child could die from suffocation CDC
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Diptheria toxin spreads systemic and fatal injury
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Diphtheria toxin B binds to host cell A inhibits protein synthesis
ADP-ribose moiety (NADH) attaches elongation factor 2 inhibited
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Treatment anti-toxin antibiotic
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Immunization against diphtheria (infant)
disease vanished in US without immunization will return toxoid (+ pertussis and tetanus) DPT neutralizing antibodies colonization not inhibited found in normal flora
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Testing immunity Schick skin test toxin
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Diphtheria toxin coded by bacteriophage tox gene
not synthesized if iron present iron-repressor complex forms inhibits expression of tox gene
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Identification - C. diphtheriae
growth Loeffler's medium stain for polyphosphate granules metachromatic polyphosphate granules (pink) cell (blue) tellurite agar reduction by bacteria tellurium precipitation black colonies
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Identification – Exotoxin production
in vivo in vitro
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C. diphtheriae should not be confused with:
diphtheroids other corynebacteria propionibacteria
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