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