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Mycobacteria
Citation preview
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MYCOBACTERIACORYNEBACTERIALecture 40
Faculty: Dr. Alvin Fox
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*KEYWORDSAcid FastTuberculosis (TB)M. tuberculosis (MDR, XDR)M. avium - M. intracellulare complexM. bovis M. lepraeTuberclePPDTuberculinMycobactinCord factorBCGLeprosy (Hansen's Disease)AIDS and TBRunyon groupsMycolic acids
DiphtheriaC. diphtheriaeLoeffler's agarTellurite agarMetachromatic bodiesDiphtheria toxinSchick testDiphtheroids
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Mycobacterium tuberculosisobligate aerobeacid-fast rods
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* M. tuberculosis major human disease healthy people problems association with AIDS multiple drug-resistance
Tuberculosis (TB, consumption)
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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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* spread from cattle
infected cattle are culled positive skin test
rarely seen in US
M. bovis
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*M. lepraeleprosymajor disease of third worldrare in US
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*Transmission -tuberculosisM. tuberculosis causes diseasehealthy 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 -tuberculosisinfiltration macrophages lymphocytesgranulomastubercules
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*Laboratory diagnosis - tuberculosisskin testing delayed hypersensitivity tuberculin protein purified derivative, PPD
X-ray
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*Positive skin test -tuberculosisindicates exposure to organismdoes not indicate active disease
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* Other minor pathogenesis factors tuberculosis
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 productiondifferentiates from other mycobacteria
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*Tuberculosispolymerase chain amplificationrapid diagnosis
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*Antibotic treatment - tuberculosisextensive time periods (e.g. 9 months)organism grows slowly, or dormanttwo or more antibiotics e.g. rifampin and isoniazidresistance minimized
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*Tuberculosis and Drug resistanceMultiple drug resistant (MDR)resistant to first line drugs Extremely drug resistant (XDR) Resistant to some of the second line drugsNearly 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. lepraecausative agentchronic disease disfigurementrarely 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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* tuberculoid few organisms active cell-mediated immunity
lepromatous many organisms immunosuppression
Leprosy
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* in vitro unculturable
in vivo growth low temperature armadillo (laboratory and native [e.g. TX]) mouse footpad
Production of M. leprae antigens and pathogenesis studies
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* lepromin skin testing
acid-fast stains skin biopsies
clinical picture
Leprosy
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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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* tuberculosis-like leprosy-like
Mycobacterial diseases
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* 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 infects AIDS patients earlier stage of disease more systemic
Mycobacteria and AIDS
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* systemic disease (versus pulmonary) greater in AIDS
lesions often lepromatous
Clinical features with AIDS
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* selected primarily for M. tuberculosis
if M. avium involved other antibiotics included
Antibiotic therapy
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*Other species pigmented or not pigmentation in the light in the dark growth fast slow
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* cellular fatty acid profiles mycolic acid profiles genetic markers
Mycobacterial species identification
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*Mycolic acidsmycobacteria longest chain lengthstrongly acid fast
nocardia intermediate chain lengthweakly acid fast
corynebacteria shortest chain lengthnot acid fast
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*Corynebacterium diphtheriaeGram positivestrict aerobepleomorphic (e.g. club-shaped)
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* member of normal flora of pharynx overgrowth upper respiratory tract pseudomembrane chocking bacteria do not spread systemicallyThe toxin does disseminates
.Diphtheria
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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 toxinspreadssystemic and fatal injury
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* B binds to host cell A inhibits protein synthesis ADP-ribose moiety (NADH) attaches elongation factor 2 inhibited
Diphtheria toxin
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*Treatment anti-toxin antibiotic
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* disease vanished in US without immunization will return
toxoid (+ pertussis and tetanus) DPT neutralizing antibodies
colonization not inhibited found in normal flora
Immunization against diphtheria (infant)
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Schick skin testtoxin
Testing immunity
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*Diphtheria toxincoded by bacteriophage tox gene not synthesized if iron present iron-repressor complex forms inhibits expression of tox gene
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growth Loeffler's medium stain for polyphosphate granules metachromatic polyphosphate granules (pink) cell (blue)
tellurite agar reduction by bacteria tellurium precipitation black colonies
Identification - C. diphtheriae
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*Identification Exotoxin productionin vivo in vitro
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* diphtheroids other corynebacteria propionibacteria
C. diphtheriae should not be confused with:
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