MYCOBACTERIA
CORYNEBACTERIA
Lecture 40
Faculty: Dr. Alvin Fox
1
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
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
5
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
10
Laboratory diagnosis tuberculosis
skin testing
delayed hypersensitivity
tuberculin
protein purified derivative, PPD
X-ray
11
Positive skin test -tuberculosis
indicates exposure to organism
does not indicate active disease
12
Other minor pathogenesis factors
tuberculosis
mycobactin
siderophore
cord factor
damages mitochondria
13
Laboratory diagnosis
M. tuberculosis
acid fast bacteria
sputum
14
Laboratory diagnosis
M. tuberculosis (culture)
grows very slowly
two weeks or longer
non-pigmented colonies
niacin production
*differentiates from other mycobacteria
15
Tuberculosis
polymerase chain amplification
rapid diagnosis
16
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
17
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
18
Vaccination
BCG vaccine
an attenuated strain of M. bovis
not effective
in US,
incidence is low
vaccination not practiced
immunization interferes with diagnosis
19
Mycobacterium leprae
20
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
21
ulcers, resorption of bone
22
worsened from careless use of hands (nerve damage)
Leprosy
tuberculoid
few organisms
active cell-mediated immunity
lepromatous
many organisms
immunosuppression
23
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
24
Leprosy
lepromin
skin testing
acid-fast stains
skin biopsies
clinical picture
25
Other mycobacterial species
(including M. avium)
infect immunocompromised host
not transmitted man-man, healthy people
M. avium common
Other species - rare
26
Mycobacterial diseases
tuberculosis-like
leprosy-like
27
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
infects AIDS patients
* earlier stage of disease
* more systemic
28
Clinical features with AIDS
systemic disease (versus pulmonary)
greater in AIDS
lesions often lepromatous
29
Antibiotic therapy
selected primarily for M. tuberculosis
if M. avium involved other antibiotics included
30
Other species
pigmented or not
pigmentation
in the light
in the dark
growth
fast
slow
31
Mycobacterial species identification
cellular fatty acid profiles
mycolic acid profiles
genetic markers
32
Mycolic acids
mycobacteria
longest chain length
strongly acid fast
nocardia
intermediate chain length
weakly acid fast
corynebacteria
shortest chain length
not acid fast
33
Corynebacterium diphtheriae
Gram positive
strict aerobe
pleomorphic (e.g. club-shaped)
34
Diphtheria
member of normal flora of pharynx
overgrowth upper respiratory tract
pseudomembrane
chocking
bacteria do not spread systemically
The toxin does disseminates
.
35
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
36
Diptheria toxin
spreads
systemic and fatal injury
37
Diphtheria toxin
B binds to host cell
A inhibits protein synthesis
ADP-ribose moiety (NADH) attaches
elongation factor 2 inhibited
38
Treatment
anti-toxin
antibiotic
39
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
40
Testing immunity
Schick skin test
-toxin
41
Diphtheria toxin
coded by bacteriophage tox gene
not synthesized if iron present
iron-repressor complex forms
inhibits expression of tox gene
42
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
43
Identification
Exotoxin production
in vivo
in vitro
44
C. diphtheriae should not be confused with:
diphtheroids
other corynebacteria
propionibacteria
45
