Mycobacteria.ppt

*

MYCOBACTERIACORYNEBACTERIALecture 40

Faculty: Dr. Alvin Fox

*

*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

*

*

Mycobacterium tuberculosisobligate aerobeacid-fast rods

*

* M. tuberculosis major human disease healthy people problems association with AIDS multiple drug-resistance

Tuberculosis (TB, consumption)

*

* M. avium- M. intracellulare complex (M. avium)

non-AIDS infection almost never AIDS major bacterial opportunist multiple drug-resistance

*

* spread from cattle

infected cattle are culled positive skin test

rarely seen in US

M. bovis

*

*M. lepraeleprosymajor disease of third worldrare in US

*

*Transmission -tuberculosisM. tuberculosis causes diseasehealthy individuals transmitted man-man airborne droplets

*

*Pathogenesis of tuberculosis infects lung

distributed within macrophages

facultative intracellular pathogen inhibits phagosome-lysosome fusion

*

*Cell-mediated immunity -tuberculosisinfiltration macrophages lymphocytesgranulomastubercules

*

*Laboratory diagnosis - tuberculosisskin testing delayed hypersensitivity tuberculin protein purified derivative, PPD

X-ray

*

*Positive skin test -tuberculosisindicates exposure to organismdoes not indicate active disease

*

* Other minor pathogenesis factors tuberculosis

mycobactin siderophore

cord factor damages mitochondria

*

*Laboratory diagnosis M. tuberculosis acid fast bacteria sputum

*

*Laboratory diagnosis M. tuberculosis (culture) grows very slowly two weeks or longer non-pigmented colonies niacin productiondifferentiates from other mycobacteria

*

*Tuberculosispolymerase chain amplificationrapid diagnosis

*

*Antibotic treatment - tuberculosisextensive time periods (e.g. 9 months)organism grows slowly, or dormanttwo or more antibiotics e.g. rifampin and isoniazidresistance minimized

*

*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

*

*Vaccination BCG vaccine an attenuated strain of M. bovis not effective

in US, incidence is low vaccination not practiced immunization interferes with diagnosis

*

*Mycobacterium leprae

*

*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

*

*ulcers, resorption of bone worsened from careless use of hands (nerve damage)

*

* tuberculoid few organisms active cell-mediated immunity

lepromatous many organisms immunosuppression

Leprosy

*

* 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

*

* lepromin skin testing

acid-fast stains skin biopsies

clinical picture

Leprosy

*

*Other mycobacterial species (including M. avium) infect immunocompromised host not transmitted man-man, healthy people M. avium common Other species - rare

*

* tuberculosis-like leprosy-like

Mycobacterial diseases

*

* 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

*

* systemic disease (versus pulmonary) greater in AIDS

lesions often lepromatous

Clinical features with AIDS

*

* selected primarily for M. tuberculosis

if M. avium involved other antibiotics included

Antibiotic therapy

*

*Other species pigmented or not pigmentation in the light in the dark growth fast slow

*

* cellular fatty acid profiles mycolic acid profiles genetic markers

Mycobacterial species identification

*

*Mycolic acidsmycobacteria longest chain lengthstrongly acid fast

nocardia intermediate chain lengthweakly acid fast

corynebacteria shortest chain lengthnot acid fast

*

*Corynebacterium diphtheriaeGram positivestrict aerobepleomorphic (e.g. club-shaped)

*

* member of normal flora of pharynx overgrowth upper respiratory tract pseudomembrane chocking bacteria do not spread systemicallyThe toxin does disseminates

.Diphtheria

*

*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

*

*Diptheria toxinspreadssystemic and fatal injury

*

* B binds to host cell A inhibits protein synthesis ADP-ribose moiety (NADH) attaches elongation factor 2 inhibited

Diphtheria toxin

*

*Treatment anti-toxin antibiotic

*

* 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)

*

*

Schick skin testtoxin

Testing immunity

*

*Diphtheria toxincoded by bacteriophage tox gene not synthesized if iron present iron-repressor complex forms inhibits expression of tox gene

*

*

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

*

*Identification Exotoxin productionin vivo in vitro

*

* diphtheroids other corynebacteria propionibacteria

C. diphtheriae should not be confused with:

*

*

*

*

*

*

*

*

*

*

*

*

*

**

*

*

*

*

*

*

*

*

**

*

*

*

*

*

*

*

*

*

*

*

*

*

*

*

*

*

*

*

*

*