“Viruses should be considered asviruses, because viruses are
viruses.”
A. Lwoff
1957
1
Why is this a quirky quote?
• “Virus” used to refer to any infectious
particle
• The word has been changed to mean
subcellular infectious particles
• In 1957, the term was still undergoing
change
2
Viruses used to be called
filterable viruses
• They were infectious particles that would
pass through a porcelain filter
• So, filterable viruses were infectious
particles that were smaller than cells
• Viruses have been known since the late
1800’s when there was a lot of work done
on tobacco mosaic virus
3
1
Figure 6.4
•
The size of a virus is small relative to the size of most bacterial and eukaryotic cells and
their organelles.
4
Viruses are:
a. Eukaryotes
b. Prokaryotes
c. Neither eukaryotes nor prokaryotes
d. I need coffee
5
Viruses are obligate, intracellular
parasites
• They can’t replicate on their own
• They need to replicate in either whole
organisms or in cell culture
– Enders and Weller
• Viruses infect bacteria, plants, and animals
– Host specificity
6
2
Viruses enter host cells
take them over, and
turn them into virus
factories
7
Viruses are nucleic acids plus a
protein coat
coat protein = capsid protein = capsomere
8
How are viruses classified?
• By the organism they infect
• By their shape
• By their genetic material
9
3
The name for a virus that infects
bacteria is a…
a. Plasmid
b. Phage
c. Vector
d. Where is the coffee?
10
Figure 6.3
(a) In this transmission electron micrograph, a bacteriophage (a virus that infects bacteria) is
dwarfed by the bacterial cell it infects.
(b) An illustration of the bacteriophage in the micrograph. (credit a: modification of work by
U.S. Department of Energy, Office of Science, LBL, PBD)
11
12
4
13
How are viruses classified?
• By the organism they infect
• By their shape
• By their genetic material
14
Figure 6.6
•
Viral capsids can be (a) helical, (b) polyhedral, or (c) have a complex shape. (credit a
“micrograph”: modification of work by USDA ARS; credit b “micrograph”: modification of
work by U.S. Department of Energy)
Viruses have regular symmetry. They self-assemble.
15
5
Figure 5.2
16
Figure 5.3a
17
Figure 5.3b
18
6
Figure 5.4a
19
20
Figure 5.5b
21
7
Coronavirus:
Enveloped virus
22
How are viruses classified?
• By the organism they infect
• By their shape
• By their genetic material
23
All cells have DS DNA!!!
The genetic material in ALL cells is:
a. DNA
b. RNA
c. DNA plus RNA
d. I need coffee
24
8
The genetic material of viruses is …
a. More diverse than cells
b. The same as in cells
c. Different, but not more diverse than cells
d. Did we learn this?
25
The genetic material of viruses is
more diverse than cells
• DNA
– SS
– DS
• RNA
– SS
– DS
This presents a problem to cells
26
Viruses enter host cells
take them over, and
turn them into virus
factories
Cells have the machinery to deal with
DS DNA, but not other configurations.
27
9
Viruses are nucleic acids plus a
protein coat
28
What machinery is need to
replicate viral particles?
• Replicate the genome
• Synthesize the capsid or coat proteins
• Synthesize any spikes or other parts of the
virus
• (envelope is derived from host cell
membrane)
29
David Baltimore chose genome
to classify viruses
• Based on genetic material
• Genetic material does not predict the shape
or whether or not a virus is enveloped
30
10
How do viruses get to mRNA?
31
How do viruses get to mRNA?
Genome type
Pathway to mRNA
dsDNA
! mRNA
ssDNA
! dsDNA ! mRNA
(+) ssRNA
(+) ssRNA (retrovirus)
acts as mRNA
! (-) ssRNA ! dsDNA ! mRNA
(-) ssRNA
! mRNA
dsRNA
! mRNA
32
How do viruses get to mRNA?
Genome type
Pathway to mRNA
dsDNA
! mRNA
ssDNA
! dsDNA ! mRNA
(+) ssRNA
(+) ssRNA (retrovirus)
acts as mRNA
! (-) ssRNA ! dsDNA ! mRNA
(-) ssRNA
! mRNA
dsRNA
! mRNA
33
11
How do viruses get to mRNA?
Genome type
Pathway to mRNA
dsDNA
! mRNA
ssDNA
! dsDNA ! mRNA
(+) ssRNA
(+) ssRNA (retrovirus)
acts as mRNA
! (-) ssRNA ! dsDNA ! mRNA
(-) ssRNA
! mRNA
dsRNA
! mRNA
34
COVID 19 is an enveloped, SS RNA virus where the RNA acts like mRNA
35
How do viruses get to mRNA?
Genome type
Pathway to mRNA
dsDNA
! mRNA
ssDNA
! dsDNA ! mRNA
(+) ssRNA
(+) ssRNA (retrovirus)
acts as mRNA
! (-) ssRNA ! dsDNA ! mRNA
(-) ssRNA
! mRNA
dsRNA
! mRNA
36
12
How do viruses get to mRNA?
Genome type
Pathway to mRNA
dsDNA
! mRNA
ssDNA
! dsDNA ! mRNA
(+) ssRNA
(+) ssRNA (retrovirus)
acts as mRNA
! (-) ssRNA ! dsDNA ! mRNA
(-) ssRNA
! mRNA
dsRNA
! mRNA
37
How do viruses get to mRNA?
Genome type
Pathway to mRNA
dsDNA
! mRNA
ssDNA
! dsDNA ! mRNA
(+) ssRNA
(+) ssRNA (retrovirus)
acts as mRNA
! (-) ssRNA ! dsDNA ! mRNA
(-) ssRNA
! mRNA
dsRNA
! mRNA
38
Figure 6.11
•
RNA viruses can contain +ssRNA that can be directly read by the ribosomes to synthesize
viral proteins. Viruses containing −ssRNA must first use the −ssRNA as a template for the
synthesis of +ssRNA before viral proteins can be synthesized.
39
13
Viruses need living cells in order to
replicate
a. True
b. False
c. It depends
d. I still need coffee
40
Will penicillin work for a cold or flu?
a. Yes
b. No
c. Sometimes, but not others
d. It depends on the severity
41
Viruses are grown in …
a. Cell culture
b. Live organisms (plants or animals)
c. By themselves
d. More than one of the above
42
14
Figure 6.18
(a) The cells within chicken eggs are used to culture different types of viruses.
(b) Viruses can be replicated in various locations within the egg, including the chorioallantoic
membrane, the amniotic cavity, and the yolk sac. (credit a: modification of work by “Chung
Hoang”/YouTube)
43
Do chickens have to worry about
getting chicken pox?
a. Yes
b. No
c. It depends
d. This is a really stupid question
44
Figure 6.17
(a) Flasks like this may be used to culture human or animal cells for viral culturing.
(b) These plates contain bacteriophage T4 grown on an Escherichia coli lawn. Clear plaques are
visible where host bacterial cells have been lysed. Viral titers increase on the plates to the left.
(credit a: modification of work by National Institutes of Health; credit b: modification of work by
American Society for Microbiology)
45
15
Figure 5.17
46
Figure 5.20
47
Figure 6.7
•
A virulent phage shows only the lytic cycle pictured here. In the lytic cycle, the phage
replicates and lyses the host cell.
48
16
Figure 6.10
•
Influenza virus is one of the few RNA viruses that replicates in the nucleus of cells. In
influenza virus infection, viral glycoproteins attach the virus to a host epithelial cell. As a
result, the virus is engulfed. Viral RNA and viral proteins are made and assembled into new
virions that are released by budding.
49
Figure 5.10
50
Figure 6.14
•
The one-step multiplication curve for a bacteriophage population follows three steps: 1)
inoculation, during which the virions attach to host cells; 2) eclipse, during which entry of
the viral genome occurs; and 3) burst, when sufficient numbers of new virions are produced
and emerge from the host cell. The burst size is the maximum number of virions produced
per bacterium.
51
17
52
If someone sneezes on you, when
might you start to sniffle?
a. 2-3 hours
b. 2-3 days
c. 2-3 weeks
d. It depends
53
If a kindergarten classmate had the
chicken pox, when might you start
to break out?
a. 2-3 hours
b. 2-3 days
c. 2-3 weeks
d. It depends
54
18
If you were accidentally stuck with
a needle while working at an AIDS
clinic, how long would you worry
about contracting AIDS?
a. 2-3 days
b. 2-3 hours
c. 2-3 months
d. It depends
55
If a classmate had COVID-19, how
long should you quarantine?
a. 2 hours
b. 2 days
c. 2 weeks
d. It depends
56
57
19
Figure 5.16
58
59
20
I had a little bird, its name was
Enza, I opened the window and
In Flew Enza
1
It has two antigenic determinants
Influenza is an enveloped, RNA virus
2
Influenza is always changing
• Antigenic drift
– Slow changes of the different H’s and N’s
– Usually changes within viruses from same host
species
• Antigenic shift
– Large changes of the different H’s and N’s
– Usually changes by having virus from different
species reassort
3
1
4
5
6
2
7
8
9
3
Week ending October 9, 2020
January 1
10
Week ending October 9, 2020
11
12
4
Week or so BEFORE COVID-19 really hit
13
Week ending October 9, 2020
January 1
14
What is it that made the H1N1 virus of 2009 so virulent?
15
5
What does this figure look like?
a. Growth curve
b. Southern blot
c. Number of people ill
Replication kinetics of H1N1 influenza viruses in polarized human airway epithelial
cells. Detroit 562 and Calu-3 cells cultured for 1 week were infected apically with virus
at an MOI of 0.01. Culture supernatants were collected, and virus titers were
determined by plaque assay. (A) Virus replication in Detroit 562 cells (human upper
respiratory epithelial cells). (B) Virus replication in Calu-3 cells (human bronchial
epithelial cells). The titer value represents the average for three independent wells. Error
bars represent the standard deviations for three independent wells.
16
What is the X axis?
What is the Y axis?
What does virus titer mean?
a. Number of infected cells
b. Number of viral particles
c. I have no idea
Replication kinetics of H1N1 influenza viruses in polarized human airway epithelial
cells. Detroit 562 and Calu-3 cells cultured for 1 week were infected apically with virus
at an MOI of 0.01. Culture supernatants were collected, and virus titers were
determined by plaque assay. (A) Virus replication in Detroit 562 cells (human upper
respiratory epithelial cells). (B) Virus replication in Calu-3 cells (human bronchial
epithelial cells). The titer value represents the average for three independent wells. Error
bars represent the standard deviations for three independent wells.
17
What is the difference
between the top and
bottom graphs?
a. The virus strains used
b. The time the experiment
ran
c. The cells that were used to
grow the virus
d. How can you tell?
Replication kinetics of H1N1 influenza viruses in polarized human airway epithelial
cells. Detroit 562 and Calu-3 cells cultured for 1 week were infected apically with virus
at an MOI of 0.01. Culture supernatants were collected, and virus titers were
determined by plaque assay. (A) Virus replication in Detroit 562 cells (human upper
respiratory epithelial cells). (B) Virus replication in Calu-3 cells (human bronchial
epithelial cells). The titer value represents the average for three independent wells. Error
bars represent the standard deviations for three independent wells.
18
6
Why did the scientists do this
part of the experiment?
a. To waste time
b. To fill up space in their paper
c. To make sure all of the viral
strains could grow under their
conditions
Replication kinetics of H1N1 influenza viruses in polarized human airway epithelial
cells. Detroit 562 and Calu-3 cells cultured for 1 week were infected apically with virus
at an MOI of 0.01. Culture supernatants were collected, and virus titers were
determined by plaque assay. (A) Virus replication in Detroit 562 cells (human upper
respiratory epithelial cells). (B) Virus replication in Calu-3 cells (human bronchial
epithelial cells). The titer value represents the average for three independent wells. Error
bars represent the standard deviations for three independent wells.
19
Why did the scientists do
the work that was in the top
graph?
a. To compare growth in the
different strains
b. To show that the strains grew in
comparable ways as a control for
another experiment
c. To take up space and confuse us
Comparison of virus replication and host proinflammatory response in polarized Calu-3 cells. (B)
Culture supernatants were collected, and virus titers were determined by plaque assay. Error bars
indicate standard deviations.(C) Assessment of gene differential expression. RNA from infected cells
was collected at 24 h p.i., reverse transcribed, and examined with a PCR array. The numbers of genes
with greater than 3-fold induction or repression are shown.
20
In the bottom graph, what
is the X axis?
a. Time
b. Amount of virus
c. Different viral strains
d. How can you tell?
Comparison of virus replication and host proinflammatory response in polarized Calu-3 cells. (B)
Culture supernatants were collected, and virus titers were determined by plaque assay. Error bars
indicate standard deviations.(C) Assessment of gene differential expression. RNA from infected cells
was collected at 24 h p.i., reverse transcribed, and examined with a PCR array. The numbers of genes
with greater than 3-fold induction or repression are shown.
21
7
In the bottom graph, what
is the Y axis?
a. Amount of virus
b. Number of genes expressed
c. Different viral strains
d. How can you tell?
Comparison of virus replication and host proinflammatory response in polarized Calu-3 cells. (B)
Culture supernatants were collected, and virus titers were determined by plaque assay. Error bars
indicate standard deviations.(C) Assessment of gene differential expression. RNA from infected cells
was collected at 24 h p.i., reverse transcribed, and examined with a PCR array. The numbers of genes
with greater than 3-fold induction or repression are shown.
22
In the bottom graph, at what
time did they sample to find
out gene expression?
a. 2 hours
b. 24 hours
c. 48 hours
d. 72 hours
e. How can you tell?
Comparison of virus replication and host proinflammatory response in polarized Calu-3 cells. (B)
Culture supernatants were collected, and virus titers were determined by plaque assay. Error bars
indicate standard deviations.(C) Assessment of gene differential expression. RNA from infected cells
was collected at 24 h p.i., reverse transcribed, and examined with a PCR array. The numbers of genes
with greater than 3-fold induction or repression are shown.
23
What can you conclude
from the bottom graph?
a. Genes were induced by all strains
b. Genes were repressed by most
strains
c. Different strains induced different
numbers of genes
d. More than one of the above
e. How can you tell?
Comparison of virus replication and host proinflammatory response in polarized Calu-3 cells. (B)
Culture supernatants were collected, and virus titers were determined by plaque assay. Error bars
indicate standard deviations.(C) Assessment of gene differential expression. RNA from infected cells
was collected at 24 h p.i., reverse transcribed, and examined with a PCR array. The numbers of genes
with greater than 3-fold induction or repression are shown.
24
8
The genes that were induced are involved in the immune response
25
Cytokines are immune proteins
• Produces by a variety of pulmonary cells
• Instigate a cascade of physiological
changes
• Trigger recruitment, proliferation, and
activation of immune cells
• Part of the non-specific immune system
26
Cytokines and influenza
27
9
28
Strains that trigger a greater
immune response will be:
a. More virulent
b. Less virulent
c. The immune response has nothing to do
with virulence
29
This is the question
• If a sufficient immune response is not
triggered, patients will die from the virus
• If too much of an immune response is
generated, set off a series of reactions that
can kill you
– Cytokine storm
30
10
“Great fleas have little fleas
upon their backs to bite ‘em
And little fleas have lesser fleas,
And so on ad infinitum.”
Augustus De Morgan
1
Infection: (not just a pathogenic state)
Really: Establishment and growth of microbes
Can be pathogenic (which is what is commonly
used)
Can be beneficial (this is what we are talking about
today)
2
1
Symbioses:
Beneficial infections
There are different kinds of
symbioses
Often symbiosis refers to nonhuman associations
3
Interactions where one species of the pair benefits
If neither benefits, that is antagonism
pathogenesis
symbiosis
4
2
Many symbiotic relationships involve plants and microbes
5
Mycorrhizae – fungi that help plant roots get nutrients
6
3
N2 Fixing bacteria in legumes
prokaryotes only: need N in every amino group, every nitrogenous
nucleic acid base
Soybeans are one of the major crops in Illinois. Soybeans are legumes
7
alfalfa plants
8
4
N2 fixing bacteria
• N=N bond (triple bond)
• Difficult to break
• Enzyme nitrogenase is found only in
prokaryotes
9
Lichens found in very dry environments
In harsh environments
10
5
Cyanobacteria and fungi together
Cyanobacteria photosynthesize and “feed” the fungus
Fungi provide a place for the cyanobacteria to live and provide some nutrients
11
Cows might ingest
grass, but they can’t
“eat” it. Mammals
can’t break down
cellulose. Only
microbes have
cellulases
12
6
Fatty acids from the
fermentation of cellulose
Cross the rumen wall and
“feed” the cow
13
Termites
Termites also “eat” cellulose, but it is the microbes
in their hindgut that break cellulose down
14
7
15
Corals
Corals are animals with photosynthetic zooxanthellae
Photosynthate “feeds” the coral
Coral provides a place for the zooxanthellae to live in the photic zone
16
8
Deep Sea thermal vents
Figure 30.4
Deep sea hydrothermal vents: at rifts in tectonic plates
17
18
9
19
20
10
Giant clams
Giant tubeworms
21
Tube worms
22
11
Trophosomes in Riftia tube worms
Trophosomes are chock-full of bacteria!
Bacteria are chemolithotrophs! (fix carbon (CO2) using chemical
oxidations for energy)
23
24
12
Deep sea thermal vents
•
•
•
•
No light so no photosynthesis
But, the microbes fix carbon
That is chemolithotrophy
That means that the microbes are fixing
carbon (CO2)
• What is the key enzyme in the Calvin
Cycle?
• RUBISCO – ribulose bisphosphate
carboxylase
25
Squid development
26
13
Without the symbiotic bacteria, the
squid doesn’t develop!
27
Vibrio fisheri in light organ
V fisheri is also found free-floating in the ocean
Free floating = planktonic
Planktonic bacteria don’t light up
When they are densely packed in a light organ, they do light up
28
14
Auto-inducer: quorum sensing molecule
Quorum sensing:
Sensing how many other cells
are around and when there are
enough, turn on some pathways
A few cells wouldn’t
produce enough light
to do any good.
A lot of cells, each
producing a little bit
of light will produce a
lot of light.
29
Figure 9.17
•
Stages in the formation and life cycle of a biofilm. (credit: modification of work by Public
Library of Science and American Society for Microbiology)
30
15
Figure 9.18
•
Short peptides in gram-positive bacteria and N-acetylated homoserine lactones in gramnegative bacteria act as autoinducers in quorum sensing and mediate the coordinated response
of bacterial cells. The R side chain of the N-acetylated homoserine lactone is specific for the
species of gram-negative bacteria. Some secreted homoserine lactones are recognized by more
than one species.
31
Many autoinducers
Don’t sweat the biochemistry!
32
16
Lux operon makes light in Vibrio fisheri
33
Biofilms and auto-inducers are also very important in pathogenesis
34
17
“There are more animals living
in the scum on the teeth in a
man’s mouth than there are men
in a whole kingdom.”
Antonie van Leeuwenhoek
Normal flora: the bacteria that live in and on you
Microbiome is the more “modern” name
There are more bacteria living in you and on you than you have your own
cells!
Infection in a beneficial sense!
35
Microbiome changes from birth and throughout a lifetime
Microbiome changes are related to the maturation of the immune system
Microbiome changes are related to what is ingested
36
18
Public Service Announcement #1
• Do not feed an infant or young child honey!
• It is difficult to get rid of Clostridium
botulinum spores in honey because it is so
viscous
• C. botulinum can colonize infant guts and
cause infant botulism
37
Public Service Announcement #2
• Nurse an infant if you (or your partner) can
do so
• The gut microbiota of nursed infants is
different than bottle fed infants
• The poop of nursed infants doesn’t smell as
bad
38
19
Different parts of our bodies have
different characteristics
– Some places on our bodies are dry
– Some places on our bodies are moist
– Some places on our bodies are anaerobic
• Gut
• Parts of our mouth
– Different places might have different pHs
– Different bacteria are going to grow in different
environmental conditions
39
40
20
Drier places:
Gm +
Moister places:
Gm –
41
Skin is different than other body
environments
• Bacteria that hang out and don’t reproduce:
– Transients
• Bacteria that live there and reproduce
– Residents: live in the dermis, not the epidermis
Skin is always sloughing off
Skin is washed
42
21
Fun fact: fermentation products are stinky.
When you were young and didn’t have hair is places, you didn’t
need deodorant!
Fun fact: bacteria love to munch on the secretions of the sweat glands
Sometimes there is a ”pathogenic” infection in the dermis
43
44
22
Mouth has hard and soft surfaces
Different bacteria live on the different surfaces
45
Biofilms form on
tooth surfaces
Biofilms are sticky
and the glycocalyx
has bacteria stick to
each other and
attracts goodies
from the food in the
mouth
46
23
Biofilms become anaerobic very
quickly.
Oxygen is used up quickly by
the bacteria as you go to more
interior portions of the biofilm
Anaerobic bacteria in the mouth
ferment and produce acids
Acids erode the matrix of the
tooth
That is tooth decay
Tooth decay: Streptococcus mutans or
Strep sobrinus
This is really a pathogenesis
Greater than 70% of children 17
and under have at least 1 dental
caries or cavity
47
48
24
Benefits of intestinal microbiome
49
There are huge environmental changes as you go through the GI tract
50
25
People used to think the stomach
was sterile because it was so
acidic!
51
52
26
Many gut bacteria are anaerobes
53
There is great variation in the
human gut microbiome
• Many people have methanogenic archae in
their guts
– Remember that methane is formed from H2 and
CO2
– Methane is odorless and colorless
– Hydrogen is odorless and colorless
– Both methane and hydrogen are flammable
54
27
A word about social
awkwardness…
• Sometimes we eat things our microbiota
can’t digest or digest too quickly
• If our microbes digest our food too quickly,
they produce more gas than we can easily
absorb
• That gas goes out one way or the other
– A burp is called eructation
– A fart is called flatulence
55
If have a high protein food
• Then there are amino acids
• Some amino acids have sulfur in their R
groups
• When those amino acids are broken down,
they make stinky products (H2S is smelly)
• Some farts are stinky
• But H2S is not flammable, just stinky
56
28
Social awkwardness
(continued…)
• Sometimes flatulence is noisy
• Sometimes flatulence is smelly
• Flatulence that is smelly is because of H2S
– The sulfur comes from amino acid fermentation
– Food like beans can be smelly because the
starch is fermented rapidly
– H2S is not flammable
57
Do not do this at home!
58
29
What gasses are made from
fermentation and digestion of
food?
• CO2 – comes from fermentation
• H2 – comes from fermentation
• CH4 – not everyone makes methane
– People have to have methanogenic bacteria as
part of their microbiome
– Scientists study this – it isn’t known why some
individuals have these bacteria and some don’t
• H2S – fermentation of proteins
59
Gut microbiome
• Changes with diet
• If you usually eat a high starch, high
protein diet, then your microbiome shifts to
be able to digest the food you eat and you
won’t fart so much
• Microbiome of vegans is often different
than that of omnivores
60
30
Microbiome studies are very,
very new
• The techniques to study microbiomes are
cutting edge and evolving rapidly
• Every few months or so, there is a
revolution in the way we can look at
microbiomes
• The “older” studies are based on very few
samples, because it was technically
impossible to do something more at that
time
61
For microbiome work
• Have to approach the conclusions (or
results) as a start rather than the full story
• Some of the microbiome work has led to
some really interesting ways of diagnosing
illness – and catching it early
– Cologuard – using a fecal sample rather than a
colonoscopy to detect colon cancer earlier than
previously possible
– (correlation is not causation – it doesn’t matter)
– Early detection for Parkinsons’ and MS
62
31
“Great fleas have little fleas
upon their backs to bite ‘em
And little fleas have lesser fleas,
And so on ad infinitum.”
Augustus De Morgan
1
Infection:
Establishment and growth of microbes
Can be pathogenic
Can be beneficial
2
Symbioses:
Beneficial infections
There are different kinds of
symbioses
3
1
mutualism
commensalism
parasitism
antagonism
competition
4
5
6
2
7
N2 Fixing bacteria in legumes
8
9
3
alfalfa plants
10
11
12
4
13
14
Termites
15
5
More termites
16
17
Corals
18
6
Deep Sea thermal vents
Figure 30.4
19
20
21
7
22
23
Tube worms
24
8
Trophosomes in Riftia tube worms
25
26
Squid development
27
9
28
Vibrio fisheri in light organ
29
Quorum sensing:
Sensing how many other cells
are around and when there are
enough, turn on some pathways
A few cells wouldn’t
produce enough light
to do any good.
A lot of cells, each
producing a little bit
of light will produce a
lot of light.
30
10
Figure 9.17
•
Stages in the formation and life cycle of a biofilm. (credit: modification of work by Public
Library of Science and American Society for Microbiology)
31
Figure 9.18
•
Short peptides in gram-positive bacteria and N-acetylated homoserine lactones in gramnegative bacteria act as autoinducers in quorum sensing and mediate the coordinated response
of bacterial cells. The R side chain of the N-acetylated homoserine lactone is specific for the
species of gram-negative bacteria. Some secreted homoserine lactones are recognized by more
than one species.
32
33
11
34
Biofilms and auto-inducers are also very important in pathogenesis
35
12
“There are more animals living
in the scum on the teeth in a
man’s mouth than there are men
in a whole kingdom.”
Antonie van Leeuwenhoek
Fun fact: There are more bacteria living in you and on you than the
number of cells that make up you
1
Normal flora change over a lifetime
We now call normal flora our microbiome
2
It takes time for our microbiomes to develop!
3
1
Public Service Announcement #1
• Do not feed an infant or young child honey!
• It is difficult to get rid of Clostridium
botulinum spores
• C. botulinum can colonize infant guts and
cause infant botulism
4
Public Service Announcement #2
• Nurse an infant if you (or your partner) can
do so
• The gut microbiota of nursed infants is
different than bottle fed infants
• The poop of nursed infants doesn’t smell as
bad
5
Different parts of our bodies have
different characteristics
– Some places on our bodies are dry
– Some places on our bodies are moist
– Some places on our bodies are anaerobic
– Different places might have different pHs
6
2
Different parts of our bodies have
different characteristics
– Some places on our bodies are dry
– Some places on our bodies are moist
– Some places on our bodies are anaerobic
– Different places might have different pHs
7
Different parts of our bodies have
different characteristics
– Some places on our bodies are dry
– Some places on our bodies are moist
– Some places on our bodies are anaerobic
– Different places might have different pHs
8
Different parts of our bodies have
different characteristics
– Some places on our bodies are dry
– Some places on our bodies are moist
– Some places on our bodies are anaerobic
– Different places might have different pHs
9
3
Different parts of our bodies have
different characteristics
– Some places on our bodies are dry
– Some places on our bodies are moist
– Some places on our bodies are anaerobic
– Different places might have different pHs
10
11
12
4
13
Start our tour on outside and
work our way in
14
Skin is a harsh environment
• It is dry
• It sloughs off
15
5
Skin is different than other body
environments
• Bacteria that hang out and don’t reproduce:
– Transients
• Bacteria that live there and reproduce
– Residents
16
Skin is different than other body
environments
• Bacteria that hang out and don’t reproduce:
– Transients
• Bacteria that live there and reproduce
– Residents
17
Skin is different than other body
environments
• Bacteria that hang out and don’t reproduce:
– Transients
• Bacteria that live there and reproduce
– Residents
18
6
19
Fun fact: fermentation products are stinky.
When you were young and didn’t have hair is places, you didn’t
need deodorant!
20
21
7
There are many different hard
and soft surfaces in the mouth.
22
23
Biofilms form on
tooth surfaces
The bacteria are
sticky – remember
glycocalyx?
The bacteria stick to
each other and draw
in more bacteria
24
8
Most of the bacteria on tooth surfaces are species of Streptococcus
Two of the major causes of dental caries are Strep mutans and Strep sobrinus
25
Biofilms become anaerobic very
quickly.
When bacteria ferment, they
produce acids.
Acids erode tooth enamel.
26
27
9
There are huge environmental changes as you go through the GI tract
28
People used to think the stomach
was sterile because it was so
acidic!
29
30
10
31
There is great variation in the
human gut microbiome
• Many people have methanogenic archae in
their guts
– Remember that methane is formed from H2 and
CO2
– Methane is odorless and colorless
– Hydrogen is odorless and colorless
– Both methane and hydrogen are flammable
32
A word about social
awkwardness…
• Sometimes we eat things our microbiota
can’t digest or digest too quickly
• If our microbes digest our food too quickly,
they produce more gas than we can easily
absorb
• That gas goes out one way or the other
– A burp is called eructation
– A fart is called flatulence
33
11
Social awkwardness
(continued…)
• Sometimes flatulence is noisy
• Sometimes flatulence is smelly
• Flatulence that is smelly is because of H2S
– The sulfur comes from amino acid fermentation
– Food like beans can be smelly because the
starch is fermented rapidly
– H2S is not flammable
34
Do not do this at home!
35
36
12
10/29/20
Pathogenicity is not the rule.
Indeed, it occurs so infrequently and
involves such a relatively small
number of species, considering the
huge population of bacteria on
earth, that it has a freakish aspect.
Lewis Thomas
1
Most microbial infections are beneficial
• Only a small proportion of microbes are pathogens
• Infectious disease is from a harmful infection
2
Kinds of (pathogenic) infections
• Primary: invasion and multiplication with damage
• Secondary: invasion subsequent to a primary infection
• Opportunistic: normally nonpathogenic flora become
pathogenic in a compromised host
3
1
10/29/20
Figure 15.5
Dose can be important
• A graph like this is used to determine LD50
by plotting pathogen concentration
against the percent of infected test
animals that have died. In this example,
the LD50 = 104 pathogenic particles.
LD 50: Dose where 50% of infected
individuals die
ID 50: Dose where 50% of exposed
individuals become infected
4
Dose can be important!
Which is more virulent?
Purple, yellow, or green?
5
We are always learning about virulence
6
2
10/29/20
7
Where do diseases come from?
• Reservoir: animate or inanimate site where disease is
maintained
• Zoonosis: disease that is transmitted from animals to humans
• Fomite: inanimate object that can harbor disease organisms
8
Where do diseases come from?
• Reservoir: animate or inanimate site where disease is
maintained
• Zoonosis: disease that is transmitted from animals to humans
• Fomite: inanimate object that can harbor disease organisms
9
3
10/29/20
10
11
12
4
10/29/20
Where do diseases come from?
• Reservoir: animate or inanimate site where disease is
maintained
• Zoonosis: disease that is transmitted from animals to humans
• Fomite: inanimate object that can harbor disease organisms
13
What does a pathogen need to do to
cause disease?
• Get to host
• Attach, colonize, or invade
• Resist host defenses
• Cause damage
14
You need to have everything all together to get disease.
If we are not exposed, we won’t get sick
15
5
10/29/20
16
17
What does a pathogen need to do to
cause disease?
• Get to host
• Attach, colonize, or invade
• Resist host defenses
• Cause damage
18
6
10/29/20
Get to the host: disease transmission
• Direct transmission: airborne
19
Get to the host: disease transmission
• Direct transmission: contact
20
Get to the host: disease transmission
• Direct transmission: vectors
21
7
10/29/20
Get to the host: disease transmission
• Direct transmission: contact
22
Get to the host: disease transmission
• Indirect transmission: fomites
23
Get to the host: disease transmission
• Indirect transmission: vehicle
24
8
10/29/20
What does a pathogen need to do to
cause disease?
• Get to host
• Attach, colonize, or invade
• Resist host defenses
• Cause damage
25
26
Figure 31.8
27
9
10/29/20
28
Figure 15.11
(a) Hyaluronan is a polymer found in the layers of epidermis that connect adjacent cells.
(b) Hyaluronidase produced by bacteria degrades this adhesive polymer in the extracellular matrix, allowing passage between
cells that would otherwise be blocked.
29
10
Disease usually results from
inconclusive negotiations for
symbiosis, an overstepping of the
line by one side or the other, a
biological misinterpretation of
borders.
Lewis Thomas
1
Infection by bacteria results in …
something good (normal flora)
something bad (pathogenesis)
2
Figure 35.3
It takes time for pathogenesis. That is the incubation time.
Prodromal stage is a time when there are minimal or no symptoms but
one is still contagious.
3
1
How many postulates
are there by Koch?
See if you can remember them
and write them down.
4
What does a pathogen need to
do to cause disease?
• Get to host
• Attach, colonize, or invade
• Resist host defenses
• Cause damage
5
What does a pathogen need to
do to cause disease?
• Get to host
• Attach, colonize, or invade
• Resist host defenses
• Cause damage
6
2
Successful pathogens have the strategies for being successful.
7
8
You need to have everything all together to get disease.
If we are not exposed, we won’t get sick
9
3
10
11
12
4
13
14
Figure 15.6
•
Shown are different portals of entry where pathogens can gain access into the body. With
the exception of the placenta, many of these locations are directly exposed to the external
environment.
15
5
16
17
18
6
Aren’t you glad you
learned your
vocabulary at the
beginning of the
semester!?!
19
20
21
7
22
Fig. 35.9
23
24
8
Toxins
1
What does a pathogen need to
do to cause disease?
• Get to host
• Attach, colonize, or invade
• Resist host defenses
• Cause damage
2
Two types of toxin
• Exotoxin
– Soluble in body fluids
– Can act distant to infection site
– Can be very potent in small amounts
• Endotoxin
– Normal part of Gram negative cell walls
– Is less potent
– Can have systemic effects
3
1
Toxins can also be classified by
where they act
• Neurotoxin
– Interfere with normal nerve transmission
• Enterotoxin
– Interfere with the GI tract
• Cytotoxin
– Kill cells or interfere with their functioning
4
Toxins can also be classified by
where they act
• Neurotoxin
– Interfere with normal nerve transmission
• Enterotoxin
– Interfere with the GI tract
• Cytotoxin
– Kill cells or interfere with their functioning
5
Toxins can also be classified by
where they act
• Neurotoxin
– Interfere with normal nerve transmission
• Enterotoxin
– Interfere with the GI tract
• Cytotoxin
– Kill cells or interfere with their functioning
6
2
7
Figure 15.13
Endotoxin
•
Lipopolysaccharide is composed of lipid A, a core glycolipid, and an O-specific
polysaccharide side chain. Lipid A is the toxic component that promotes inflammation and
fever.
8
Endotoxin: the LPS in a normal Gram negative cell wall
This is why it is not wise to give bacteriolytic antibiotics.
9
3
10
Fig. 35.8
Nasty things that
endotoxin does
11
Exotoxins
• Soluble in body fluids
• Can act distant from primary infection site
• Are more potent than endotoxins
• Defined by type of action
– Cytotoxin
– Neurotoxin
– Enterotoxin
12
4
Cytotoxins lyse cells
13
Table 35.4
14
A-B toxins are synthesized in subunits (part A and part B)
They become active when the subunits are put together
15
5
Figure 15.14
(a) In A-B toxins, the B component binds to the host cell through its interaction with specific cell surface receptors.
(b) The toxin is brought in through endocytosis.
(c) Once inside the vacuole, the A component (active component) separates from the B component and the A component
gains access to the cytoplasm. (credit: modification of work by “Biology Discussion Forum”/YouTube)
16
17
Diptheria toxin causes a pseudomembrane in the back of the throat
which can suffocate an infected individual
18
6
Figure 15.15
•
The mechanism of the diphtheria toxin inhibiting protein synthesis. The A subunit
inactivates elongation factor 2 by transferring an ADP-ribose. This stops protein elongation,
inhibiting protein synthesis and killing the cell.
19
It might be a relief to
know that we have
conquered some
diseases with antibiotics
and vaccines
20
Many of the toxins work via secondary messengers.
21
7
What major
sporting event has
a link to a
microbial toxin?
I always ask this in class, nobody has guessed it yet.
And I have taught this class each and every semester for more than 25 years.
22
23
24
8
One more set of examples for
exotoxins
• Clostridium botulinum
– Flaccid paralysis
• Clostridium tetani
– Rigid paralysis
25
Figure 15.16
•
Mechanisms of botulinum and tetanus toxins. (credit micrographs: modification of work by
Centers for Disease Control and Prevention)
26
27
9
No, you don’t need to know the details
28
Famous painting by Sir Charles Bell
29
30
10
Alleged Botox Botulism Cases Traced Back
To Fort Lauderdale Clinic
Health officials are asking hospitals across South
Florida to watch for cases of botulism after four
people fell gravely ill after they thought they
received botox injections at a Fort Lauderdale
clinic.
The injections were given at Advanced Integrated
Medical Center along Oakland Park Boulevard. One
of the sick people is the clinic’s owner, Dr. Bach
McComb, 47. He and his girlfriend, 34, are both in
critical condition in a New Jersey hospital suffering
botulism symptoms.
A second couple is in critical condition in a Palm Beach County hospital
suffering similar symptoms. The unidentified man and woman, who are in
their 50s, were admitted to the hospital on Thanksgiving Day, just 24 hours
after receiving botox treatments at Integrated Medical Center.
Officials think they might have contracted the illness from contaminated doses
of botox or some sort of synthetic gray market botox that is often made in
Europe.
31
11
10/29/20
More on Koch’s Postulates
1
Die Ätiologie der Milzbrand-Krankheit, begründet auf die
Entwicklungsgeschichte des Bacillus Anthracis.1)
Von
Dr. R. Koch,
Kreisphysikus in Wollstein.
Hierzu Tafel I.
Koch published his postulates in 1876.
I. Einleitung. Seit dem Auffinden der stäbchenförmigen Körper im Blute der an
Milzbrand gestorbenen Tiere hat man sich vielfach Mühe gegeben, dieselben als die Ursache für die direkte Übertragbarkeit dieser Krankheit ebenso wie für das sporadische
Auftreten derselben, also als das eigentliche Kontagium des Milzbrands nachzuweisen.
I n neuerer Zeit hatte sich hauptsächlich D a v a i n e mit dieser Aufgabe beschäftigt
und, gestützt auf zahlreiche Impf versuche mit frischem oder getrocknetem stäbchenhaltigen Blute, mit aller Entschiedenheit dahin ausgesprochen, daß die Stäbchen Bakterien
seien und nur beim Vorhandensein dieser Bakterien das Milzbrandblut die Krankheit
von neuem zu erzeugen vermöge. Die ohne nachweisbare direkte Übertragung entstandenen Milzbranderkrankungen bei Menschen und Tieren führte er auf die Verschleppung
der, wie er entdeckt hatte, im getrockneten Zustande lange Zeit lebensfähig bleibenden
Bakterien durch Luftströmungen, Insekten und dergleichen zurück. Die Verbreitungsweise des Milzbrandes schien hiermit vollständig klar gelegt zu sein.
Dennoch fanden diese von D a v a i n e aufgestellten Sätze von verschiedenen
Seiten Widerspruch. Einige Forscher wollten nach Impfung mit bakterienhaltigem Blute
tödlichen Milzbrand erzielt haben, ohne daß sich nachher Bakterien im Blute fanden,
und umgekehrt ließ sich wieder durch Impfung mit diesem bakterienfreien Blute Milzbrand hervorrufen, bei welchem Bakterien im Blute vorhanden waren. Andere machten
darauf aufmerksam, daß der Milzbrand nicht allein.von einem Kontagium abhänge,
welches oberhalb der Erde verbreitet werde, sondern daß diese Krankheit in einem
unzweifelhaften Zusammenhange mit Bodenverhältnissen stehe. Wie würde sonst zu
erklären sein, daß das endemische Vorkommen des Milzbrandes an feuchten Boden,
also namentlich an Elußtäler, Sumpfdistrikte, Umgebungen von Seen gebunden ist; daß
ferner die Zahl der Milzbrandfälle in nassen Jahren bedeutender ist und sich hauptsächlich auf die Monate August und September, in welchen die Kurve der Bodenwärme ihren
Gipfelpunkt erreicht, zusammendrängt, daß in den Milzbranddistrikten, sobald die Herden
an bestimmte Weiden und Tränken geführt werden, jedesmal eine größere Anzahl von
Erkrankungen unter den Tieren eintritt.
His method of systematically finding the
causative agent for a disease using the
techniques available in his time was
revolutionary and the time was right for
this approach.
However, Koch published papers in 1884
and 1893 that suggested that there were
exceptions or nuances to his postulates.
2
*) Cohns Beiträge zur Biologie der Pflanzen, Bd. II, Heft 2, p. 277. Breslau 1870, J. U. Kerns
Verlag.
Can you remember Koch’s postulates?
If we were face-to-face, I would write them on the board as
students called them out.
3
1
10/29/20
Figure 15.4
•
The steps for confirming that a pathogen is the cause of a particular disease using Koch’s
postulates.
4
Koch’s Postulates
1. Microbe is ALWAYS present in a diseased host and
NEVER present in a healthy host.
2. Isolate the microbe away from the host in pure
culture.
3. Isolated microbe causes the disease in a health,
susceptible host.
4. Reisolate the original microbe from the artificially
infected host.
5
Koch’s Postulates
1. Microbe is ALWAYS present in a diseased host and
NEVER present in a healthy host.
That is an absolute.
2. Isolate the What
microbe
frompathogens
the host
inarepure
about away
opportunistic
that
usually benign
normal flora?
culture.
Some pathogens don’t need to be present – sometimes just the
toxin needs to be present to cause the disease.
3. Isolated microbe causes the disease in a health,
susceptible host.
4. Reisolate the original microbe from the artificially
infected host.
6
2
10/29/20
Koch’s Postulates
1. Microbe is ALWAYS present in a diseased host and
NEVER present in a healthy host.
2. Isolate the microbe away from the host in pure
culture.
3. Isolated microbe
We can’tcauses
grow everything
the disease
in pure culture.
in a health,
Sometimes we don’t know the medium, sometimes we need to
susceptible
host. have a live host.
We have molecular techniques now so that sometimes we don’t
even grow
the microbe
at all.the artificially
4. Reisolate the original
microbe
from
infected host.
7
Koch’s Postulates
Is there an appropriate host for each pathogen?
1. Microbe Ifisyou
ALWAYS
present
a diseased
host
have a disease
with ain
narrow
host range,
how and
can you
and ethically do this step?
NEVER present in amorally
healthy
host.
This also assumes that it is solely one causative agent, with no comorbidities
2. Isolate the microbe away from the host in pure
culture.
3. Isolated microbe causes the disease in a health,
susceptible host.
4. Reisolate the original microbe from the artificially
infected host.
8
Koch’s Postulates
1. Microbe is ALWAYS present in a diseased host and
NEVER present in a healthy host.
youmicrobe
couldn’taway
do #3,
thenthe
you
can’t
do #4!
2. IsolateIfthe
from
host
in pure
culture.
3. Isolated microbe causes the disease in a health,
susceptible host.
4. Reisolate the original microbe from the artificially
infected host.
9
3
10/29/20
So, are Koch’s postulates a bunch of
baloney and a waste of time?
! They provide a great framework for cause and effect
for many, many microbial diseases.
! They provided a way for scientists to study microbial
disease systematically.
! Koch and his students gave us many of the methods
and tools that are still used in microbiology.
! We have to look at them like a guide rather than the
gospel truth.
10
4
3/30/22
What does a pathogen need to do to
cause disease?
• Get to host
• Attach, colonize, or invade
• Resist host defenses
• Cause damage
1
Wearing face coverings reduces exposure, if you are not exposed, you are not going to get sick
You need to have everything all together to get disease.
If we are not exposed, we won’t get sick
2
1
3/30/22
Die Ätiologie der Milzbrand-Krankheit, begründet auf die
Entwicklungsgeschichte des Bacillus Anthracis.1)
Von
Dr. R. Koch,
Kreisphysikus in Wollstein.
Hierzu Tafel I.
Koch published his postulates in 1876.
I. Einleitung. Seit dem Auffinden der stäbchenförmigen Körper im Blute der an
Milzbrand gestorbenen Tiere hat man sich vielfach Mühe gegeben, dieselben als die Ursache für die direkte Übertragbarkeit dieser Krankheit ebenso wie für das sporadische
Auftreten derselben, also als das eigentliche Kontagium des Milzbrands nachzuweisen.
I n neuerer Zeit hatte sich hauptsächlich D a v a i n e mit dieser Aufgabe beschäftigt
und, gestützt auf zahlreiche Impf versuche mit frischem oder getrocknetem stäbchenhaltigen Blute, mit aller Entschiedenheit dahin ausgesprochen, daß die Stäbchen Bakterien
seien und nur beim Vorhandensein dieser Bakterien das Milzbrandblut die Krankheit
von neuem zu erzeugen vermöge. Die ohne nachweisbare direkte Übertragung entstandenen Milzbranderkrankungen bei Menschen und Tieren führte er auf die Verschleppung
der, wie er entdeckt hatte, im getrockneten Zustande lange Zeit lebensfähig bleibenden
Bakterien durch Luftströmungen, Insekten und dergleichen zurück. Die Verbreitungsweise des Milzbrandes schien hiermit vollständig klar gelegt zu sein.
Dennoch fanden diese von D a v a i n e aufgestellten Sätze von verschiedenen
Seiten Widerspruch. Einige Forscher wollten nach Impfung mit bakterienhaltigem Blute
tödlichen Milzbrand erzielt haben, ohne daß sich nachher Bakterien im Blute fanden,
und umgekehrt ließ sich wieder durch Impfung mit diesem bakterienfreien Blute Milzbrand hervorrufen, bei welchem Bakterien im Blute vorhanden waren. Andere machten
darauf aufmerksam, daß der Milzbrand nicht allein.von einem Kontagium abhänge,
welches oberhalb der Erde verbreitet werde, sondern daß diese Krankheit in einem
unzweifelhaften Zusammenhange mit Bodenverhältnissen stehe. Wie würde sonst zu
erklären sein, daß das endemische Vorkommen des Milzbrandes an feuchten Boden,
also namentlich an Elußtäler, Sumpfdistrikte, Umgebungen von Seen gebunden ist; daß
ferner die Zahl der Milzbrandfälle in nassen Jahren bedeutender ist und sich hauptsächlich auf die Monate August und September, in welchen die Kurve der Bodenwärme ihren
Gipfelpunkt erreicht, zusammendrängt, daß in den Milzbranddistrikten, sobald die Herden
an bestimmte Weiden und Tränken geführt werden, jedesmal eine größere Anzahl von
Erkrankungen unter den Tieren eintritt.
His method of systematically finding the
causative agent for a disease using the
techniques available in his time was
revolutionary and the time was right for
this approach.
However, Koch published papers in 1884
and 1893 that suggested that there were
exceptions or nuances to his postulates.
3
*) Cohns Beiträge zur Biologie der Pflanzen, Bd. II, Heft 2, p. 277. Breslau 1870, J. U. Kerns
Verlag.
Figure 15.4
• The steps for confirming that a pathogen is the cause of a particular disease using Koch’s postulates.
4
2
3/30/22
Koch’s Postulates
1. Microbe is ALWAYS present in a diseased host and
NEVER present in a healthy host.
2. Isolate the microbe away from the host in pure
culture.
3. Isolated microbe causes the disease in a health,
susceptible host.
4. Reisolate the original microbe from the artificially
infected host.
5
Koch’s Postulates
1. Microbe is ALWAYS present in a diseased host and
NEVER present in a healthy host.
That
is an absolute.
2. Isolate the microbe away
from
the host in pure
What about opportunistic pathogens that are usually benign
culture.
normal flora?
3.
Some pathogens don’t need to be present – sometimes just the
toxincauses
needs to be
present
to cause
disease.
Isolated microbe
the
disease
inthe
a health,
susceptible Clostridium
host. perfringens:
toxin causes food poisoning
Infection causes gas gangrene
4. Reisolate the original microbe from the artificially
infected host.
6
3
3/30/22
Koch’s Postulates
1. Microbe is ALWAYS present in a diseased host and
NEVER present in a healthy host.
2. Isolate the microbe away from the host in pure
culture.
3. Isolated microbe
the disease
in a health,
We can’tcauses
grow everything
in pure culture.
Sometimes
we
don’t
know
the
medium,
sometimes
we need to
susceptible host.
4.
have a live host.
We have molecular techniques now so that sometimes we don’t
even grow
the microbe
at all.the artificially
Reisolate the original
microbe
from
infected host.
7
Koch’s Postulates
Is there an appropriate host for each pathogen?
have a disease
with ainnarrow
host range,
how and
can you
1. Microbe Ifisyou
ALWAYS
present
a diseased
host
morally and ethically do this step?
NEVER This
present
in a healthy host.
also assumes that it is solely one causative agent, with no comorbidities
2. Isolate the microbe away from the host in pure
culture.
3. Isolated microbe causes the disease in a healthy,
susceptible host.
4. Reisolate the original microbe from the artificially
infected host.
8
4
3/30/22
Koch’s Postulates
1. Microbe is ALWAYS present in a diseased host and
NEVER present in a healthy host.
2. IsolateIfthe
from
host
in pure
youmicrobe
couldn’taway
do #3,
thenthe
you
can’t
do #4!
culture.
3. Isolated microbe causes the disease in a health,
susceptible host.
4. Reisolate the original microbe from the artificially
infected host.
9
Koch’s postulates assume:
1 organism = 1 disease
• Not always true
• Some organisms cause more than 1 disease
• Cl. perfringes (gas gangrene and food poisoning)
• Staph aureus toxin! food poisoning / toxic shock syndrome/zits
• Strep pyogenes ! strep throat/ scarlet fever/rheumatic fever/impetigo
10
5
3/30/22
So, are Koch’s postulates a bunch of baloney
and a waste of time?
” They provide a great framework for cause and effect
for many, many microbial diseases.
” They provided a way for scientists to study microbial
disease systematically.
” Koch and his students gave us many of the methods
and tools that are still used in microbiology.
” We have to look at them like a guide rather than the
gospel truth.
11
Koch’s Postulates
• If study something systematically and reproducibly, it is SCIENCE
• Koch and his students allowed us to think about infectious disease as
something that is scientific
• Koch and his students gave us the tools to study infectious disease
• Took infectious disease out of the mysterious way of thinking, out of
being Divine Providence, and into science
• Koch’s postulates are a guide for us to study disease
12
6
3/30/22
Any successful pathogen survives
13
14
7
3/30/22
What does a pathogen need to do to
cause disease?
• Get to host
• Attach, colonize, or invade
• Resist host defenses
Immunology: next week or in a few weeks
Cat and mouse game between host and pathogens
• Cause damage
15
Two types of toxin
• Exotoxin
• Soluble in body fluids
• Can act distant to infection site
• Can be very potent in small amounts
• Endotoxin
• Normal part of Gram negative cell walls
• Is less potent
• Can have systemic effects
16
8
3/30/22
17
Endotoxin: the LPS in a normal Gram negative cell wall
This is why it is not wise to give bacteriolytic antibiotics.
Bacteriolytic antibiotics lyse cell walls
Releases all of the endotoxin all at once
18
9
3/30/22
19
Activating immune system!
Nasty things that endotoxin does
20
10
3/30/22
Exotoxins
• Soluble in body fluids
• Can act distant from primary infection site
• Are more potent than endotoxins
• Defined by type of action
• Cytotoxin
• Neurotoxin
• Enterotoxin
21
Toxins can also be classified by where they act
• Neurotoxin
• Interfere with normal nerve transmission
• Enterotoxin
• Interfere with the GI tract
• Cytotoxin
• Kill cells or interfere with their functioning
22
11
3/30/22
Toxins can also be classified by where they act
• Neurotoxin
• Interfere with normal nerve transmission
• Enterotoxin
• Interfere with the GI tract
• Cytotoxin
• Kill cells or interfere with their functioning
23
Toxins can also be classified by where they act
• Neurotoxin
• Interfere with normal nerve transmission
• Enterotoxin
• Interfere with the GI tract
• Cytotoxin
• Kill cells or interfere with their functioning
24
12
3/30/22
Successful
pathogens can
do damage
25
A-B toxins are synthesized in subunits (part A and part B)
They become active when the subunits are put together
A/B toxins have 2 parts: an A part and a B part
26
13
3/30/22
Figure 15.14
(a)
In A-B toxins, the B component binds to the host cell through its interaction with specific cell surface receptors.
(b)
The toxin is brought in through endocytosis.
(c)
Once inside the vacuole, the A component (active component) separates from the B component and the A component gains access to the cytoplasm. (credit:
modification of work by “Biology Discussion Forum”/YouTube)
27
Figure 15.15
• The mechanism of the diphtheria toxin inhibiting protein synthesis. The A subunit inactivates elongation factor 2 by
transferring an ADP-ribose. This stops protein elongation, inhibiting protein synthesis and killing the cell.
28
14
3/30/22
It might be a relief to know that
we have conquered some
diseases with antibiotics and
vaccines
29
Many of the toxins work via secondary messengers.
30
15
3/30/22
31
32
16
3/30/22
33
One more set of examples for exotoxins
• Clostridium botulinum
• Flaccid paralysis
• Clostridium tetani
• Rigid paralysis
Antitoxin is often very important in treating diseases with exotoxins: diptheria
Antitoxin is not commonly available: generally try to prevent diseases with really, really bad toxins
34
17
3/30/22
Figure 15.16
• Mechanisms of botulinum and tetanus toxins. (credit micrographs: modification of work by Centers for Disease Control and
Prevention)
Both are neurotoxins: rigid is rigid paralysis, botulism flaccid paralysis
35
Famous painting by Sir Charles Bell
Tetanus: rigid
Death by asphyxian
36
18
3/30/22
Botox: flaccid paralysis
Used cosmetically
Used for neurological ailments
37
Alleged Botox Botulism Cases Traced Back
To Fort Lauderdale Clinic
Health officials are asking hospitals across South
Florida to watch for cases of botulism after four
people fell gravely ill after they thought they
received botox injections at a Fort Lauderdale
clinic.
The injections were given at Advanced Integrated
Medical Center along Oakland Park Boulevard. One
of the sick people is the clinic’s owner, Dr. Bach
McComb, 47. He and his girlfriend, 34, are both in
critical condition in a New Jersey hospital suffering
botulism symptoms.
A second couple is in critical condition in a Palm Beach County hospital
suffering similar symptoms. The unidentified man and woman, who are in
their 50s, were admitted to the hospital on Thanksgiving Day, just 24 hours
after receiving botox treatments at Integrated Medical Center.
Officials think they might have contracted the illness from contaminated doses
of botox or some sort of synthetic gray market botox that is often made in
Europe.
38
19
Order an Essay Now & Get These Features For Free:
Turnitin Report
Formatting
Title Page
Citation
Outline
