As late as the 1800s, causes and

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As late as the 1800s, causes and cures of TB
remained mysterious
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Then along came Robert Koch
December 11, 1843- May 27, 1910
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You may not remember me but Ill bet youve heard
of my Postulates
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I developed tests to determine whether an
infectious agent causes a given disease
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1.The microorganism must be found in abundance
in all organisms suffering from the disease,
but not in healthy organisms.
2.The microorganism must be isolated from a
diseased organism and grown in pure
culture 3.The cultured microorganism should
cause disease when introduced into a healthy
organism. 4.The microorganism must be
re-isolated from the inoculated, diseased
experimental host and identified as being
identical to the original specific causative
agent.
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I know its a hard act to follow, but I wasnt
done yet
In 1882 while working in Berlin I discovered the
tuberculosis bacteria and the means of culturing
it
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The Nobel Prize in Physiology or Medicine 1905
In 1882 while working in Berlin I discovered the
tuberculosis bacteria and the means of culturing
it
Nobelprize.org
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Our star Mycobacterium Tuberculosis
Arent I pretty?
Mycobacterium Tuberculosis on Lowenstein-Jensen
medium
Mycobacterium Tuberculosis (scanning EM)
Images from CDC
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But I am very hard to grow
Mycobacterium Tuberculosis on Lowenstein-Jensen
medium
Mycobacterium Tuberculosis (scanning EM)
Images from CDC
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I am an Obligate aerobe and grow very slowly
15-20 hour doubling vs. 30 minutes for E. coli
I require 6-8 weeks to grow on plates!
Mycobacterium Tuberculosis on Lowenstein-Jensen
medium
Mycobacterium Tuberculosis (scanning EM)
Images from CDC
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I am acid-fast so you can ID me using special
stains
Mycobacterium Tuberculosis on Lowenstein-Jensen
medium
Mycobacterium Tuberculosis (scanning EM)
Images from CDC
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Acid-fastness refers to resistance to
decolorization by acids during staining
procedures The most common staining technique is
Ziehl-Neelsen stain, in which the bacteria are
stained bright red.
Red is my favorite color!
Mycobacterium tuberculosis (stained red) in
tissue (blue).
Mycobacterium tuberculosis (stained red) in sputum
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Heres my family tree
Staph. aureus
TB bug
E. coli
Genome Research 12, 1080-1090 (2002)
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Were distant cousins
Staph. aureus
TB bug
E. coli
You
Genome Research 12, 1080-1090 (2002)
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Mycobacterial relatives of the TB bug cause
other diseases
Mycobacterium africanum causes up to
one-third Of TB cases in West Africa. Milder in
non-immunocompromised patient
Mycobacterium leprae causes Leprosy (Hansens
disease)
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Mycobacterial relatives of the TB bug cause
other diseases
Mycobacterium africanum causes up to
one-third Of TB cases in West Africa. Milder in
non-immunocompromised patient
Mycobacterium leprae causes Leprosy (Hansens
disease)
Mycobacterium bovis. Causes Bovine TB. Killed
many farm animals inn first half of 20th century.
Destroyed by pasteurization. Causes TB in
developing world.
Mycobacterium avium. Causes TB in birds.
Also affects HIV patients and other
immunocompromised people
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Heres how it usually starts
Left untreated, a person with active TB will
infect 10-15 other people per year
World Lung Foundation (2008) and
http//pathport.vbi.vt.edu/pathinfo/pathogens/Tube
rculosis_2.html
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TB lives INSIDE human cells!
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It takes advantage of our bodies own
first-responders
Macrophage
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Macrophages are responsible for Phagocytosis of
bacteria and other foreign cells and for
activation of other immune cells
Macrophage
Bacteria
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Macrophages love to eat bacteria
Yum-yum!
www.nyas.org/.../ images/carroll3_small.jpg
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Normally ingested bacteria and other things get
sent to the lysosome for destruction by low pH
and proteolysis
Uh oh!
bacterium
Ahhhhhhh..
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But the TB bacterium has a better idea-- It
remodels the endosome to be its new home!
Very cozy
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The infected macrophage calls for help generating
a granuloma
www.nyas.org/.../ images/carroll3_small.jpg
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Lets look at that in a bit more detail
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Infected macrophages send signals that recruit
nearby lymphocytes
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Uninfected macrophages and Lymphocytes surround
the infected cells
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They encase the infected cells in a cage of
matrix proteins where they can stay for years!
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But if the immune system is compromised by
malnutrition, HIV or old age.