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MYCOBACTERIA CORYNEBACTERIA Lecture 40. Faculty: Dr. Alvin Fox. 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
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MYCOBACTERIACORYNEBACTERIALecture 40 Faculty: Dr. Alvin Fox
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 KEYWORDS
Mycobacterium tuberculosis obligate aerobe acid-fast rods
Tuberculosis (TB, consumption) • M. tuberculosis • major human disease • healthy people • problems • association with AIDS • multiple drug-resistance
M. avium- M. intracellulare complex (M. avium) • non-AIDS • infection almost never • AIDS • major bacterial opportunist • multiple drug-resistance
M. bovis • spread from cattle • infected cattle are culled • positive skin test • rarely seen in US
M. leprae • leprosy • major disease of third world • rare in US
Transmission -tuberculosis • M. tuberculosis causes disease • healthy individuals • transmitted man-man • airborne droplets
Pathogenesis of tuberculosis • infects lung • distributed within macrophages • facultative intracellular pathogen • inhibits phagosome-lysosome fusion
Cell-mediated immunity -tuberculosis • infiltration • macrophages • lymphocytes • granulomas • tubercules
Laboratory diagnosis - tuberculosis • skin testing • delayed hypersensitivity • tuberculin • protein purified derivative, PPD • X-ray
Positive skin test -tuberculosis • indicates exposure to organism • does 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 production • differentiates from other mycobacteria
Tuberculosis • polymerase chain amplification • rapid diagnosis
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
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
Vaccination • BCG vaccine • an attenuated strain of M. bovis • not effective • in US, • incidence is low • vaccination not practiced • immunization interferes with diagnosis
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
ulcers, resorption of bone • worsened from careless use of hands (nerve damage)
Leprosy • tuberculoid • few organisms • active cell-mediated immunity • lepromatous • many organisms • immunosuppression
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
Leprosy • lepromin • skin testing • acid-fast stains • skin biopsies • clinical picture
Other mycobacterial species (including M. avium) • infect immunocompromised host • not transmitted man-man, healthy people • M. avium – common • Other species - rare
Mycobacterial diseases • tuberculosis-like • leprosy-like
Mycobacteria and AIDS • M. aviumis 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
Clinical features with AIDS • systemic disease (versus pulmonary) • greater in AIDS • lesions often lepromatous
Antibiotic therapy • selected primarily for M. tuberculosis • if M. avium involved other antibiotics included
Other species • pigmented or not • pigmentation • in the light • in the dark • growth • fast • slow
Mycobacterial species identification • cellular fatty acid profiles • mycolic acid profiles • genetic markers
Mycolic acids • mycobacteria • longest chain length • strongly acid fast • nocardia • intermediate chain length • weakly acid fast • corynebacteria • shortest chain length • not acid fast
Corynebacterium diphtheriae Gram positive strict aerobe pleomorphic (e.g. club-shaped)
Diphtheria • member of normal flora of pharynx • overgrowth upper respiratory tract • pseudomembrane • chocking • bacteria do not spread systemically • The toxin does disseminates • .
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 toxin • spreads • systemic and fatal injury
Diphtheria toxin • B binds to host cell • A inhibits protein synthesis • ADP-ribose moiety (NADH) attaches • elongation factor 2 inhibited
Treatment • anti-toxin • antibiotic
Immunization against diphtheria (infant) • diseasevanished in US • without immunization will return • toxoid (+ pertussis and tetanus) DPT • neutralizing antibodies • colonization not inhibited • found in normal flora
Testing immunity • Schick skin test • toxin
Diphtheria toxin • coded by bacteriophage tox gene • not synthesized if iron present • iron-repressor complex forms • inhibits expression of tox gene
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
Identification – Exotoxin production • in vivo • in vitro
C. diphtheriae should not be confusedwith: • diphtheroids • other corynebacteria • propionibacteria