Transcript Pathogenicity

Pathogenicity
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What makes some
bacteria dangerous?
Disease Process
Infection
Virulence factors
Pathogenicity
No virulence factors
Silent infection
Environment
Disease
Symptoms
Pathogenicity
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Ability to cause
disease - this is
qualitative yes or no
Virulence - degree of
pathogenicity
Requires that
 organism survive host
defenses
 cause damage
 Have virulence factors
Bacterial virulence factors for adherence,
colonization, and invasiveness
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Virulence
• varies with infectivity
and severity of damage
Infectivity is often the
single most important
feature; the microbe must
be able to "stick" around
• Attachment molecules
for bacteria are termed
adhesins such as…..
Microbes often enter cells
to establish as
intracellular parasites
Some microbes move around the body from
site of infection - invasiveness
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Within cells that circulate
Through cells- in and out
Through junctions that
they weaken
Cell entry of bacteria is
typically by phagocytosis
• Professional
phagocytes
• Non phagocytic cells
are induced to local
phagocytosis (Type III
secretion)
Salmonella entering
gut cells
Spreading factors - enzymes to destroy
intercellular cement
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collagenase,
hyaluronidase,
fibrinolysin,
lecithinase,
streptokinase
Gangrene of the
hand
Need to avoid host defenses to survive
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Antiphagocytic factors
• Capsules, cell wall proteins
• leukocidin
• coagulase (walls off)
• survival in WBC - intracellular parasites
(mycobacteria, Listeria)
IgA protease - Neisseria
Opportunistic pathogens need compromised host
N. meningitidis
crosses blood-brain
barrier
Need for iron to survive
How do bacteria damage the host?
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ENDOTOXIN vs
EXOTOXIN
• Composition
LPS (lipidA) vs
protein(immunogenic)
• Toxic response
fever and shock vs
specific affect
• Typically produced by
gram negatives vs gram
positives and negatives
What is the mode of action of each of these
exotoxins?
 diphtheria
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tetanus
botulism
cholera
pertussis
Anthrax
Samonella and E.coli
Botulism and tetanus are produced by
endospore-forming bacteria
Cholera deaths are
preventable
(iii) Salmonella
Salmonella typhimurium - rod prokaryote (dividing); note the flagella. Causes salmonellosis
(food poisoning). (x 20,800) © Dr Dennis Kunkel, University of Hawaii. Used with permission
Based on genetic studies there is a single species of
Salmonella (Salmonella enterica).
Using appropriate antibodies more than 2000
antigenic "types" have been recognized.
Only a few types that are commonly associated
with characteristic human diseases 1. S. enteritidis
2. S. cholerae-suis
3. S. typhi
1. Salmonellosis, the common salmonella infection,
is caused by a variety of serotypes (most
commonly S. enteritidis) and is transmitted from
contaminated food (such as poultry and eggs).
2. It does not have a human reservoir.
3. It usually presents as a gastroenteritis
• nausea
• vomiting
• non-bloody stool
4. The disease is usually self-limiting (2 - 5 days).
Like Shigella, salmonella invade the epithelium
and do not produce systemic infection.
In uncomplicated cases of salmonellosis, which
are the vast majority, antibiotic therapy is not
useful.
S. cholerae-suis (seen much less commonly)
causes septicemia after invasion.
In this case, antibiotic therapy is required.
The severest form of salmonella infections is called
"typhoid" or enteric fever.
Typhoid is caused by Salmonella typhi.
This disease is rarely seen in the Australia.
Typhoid is one of the historical causes of
widespread epidemics and still causes epidemics in
the third world.
Salmonella typhi
• The organism is transmitted from:
1. a human reservoir
2. in the water supply (if sanitary conditions
are poor)
3. in contaminated food
• It initially invades the intestinal epithelium and
during this acute phase, gastrointestinal
symptoms are noted.
• The organisms penetrates (usually within the
first week) and passes into the bloodstream
where it is disseminated in macrophages.
• Typical features of a systemic bacterial infection
are noted.
• The septicemia usually is temporary with the
organism finally lodging in the gall bladder.
• Organisms are shed into the intestine for some
weeks.
• At this time the gastroenteritis (including
diarrhea) is noted again.
• The Vi (capsular) antigen plays a role in the
pathogenesis of typhoid.
• A carrier state is common; thus one person e.g.
a food handler can cause a lot of spread.
• Antibiotic therapy is essential.
• Vaccines are not widely effective and not
generally used.
Pertussis toxin helps bacteria bind to
cilia and to kill cells
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Pentameric B subunit
delivers A subunit
ADP-ribosylates
protein that is part of
signal transduction
mechanism at cell
surface
Kills cells in
respiratory tract
Anthrax still poses a threat
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Three proteins
• Lethal factor (LF)
• Edema factor (EF)
• Protective antigen (PA)
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PA binds forms a
heptamer to which EF
and LF bind
Endocytosis and pH
change cause fusion of PA
with vesicle and release of
LF and EF
Inhibit cell signalling and
cause cell death
Damage is often caused by the host
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Cytokine release
Antibody cross
reactions
Immune complex
deposition
What about viruses?
Adherence - access to cell with receptor
 Maintenance - ability to replicate
 Spread - no destruction in or out of cell
 Damage - lysis of cells, cytokine release,
cross reactions of immune response
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Host Defenses
Innate Resistance - genetic
 Nonspecific - present at all times but varies
with portal of entry; directed against most
bacteria
 Specific immunity - induced only after
exposure; specific to the agent
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Nonspecific defenses
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Skin and mucous
membrane surfaces
• physical barriers
Characteristics of skin
• dry and cool
• low pH
• chemicals - fatty acids,
lysozyme
• competition from
normal flora
• lymphoid cells beneath
surface - magainins
How does mucous membrane differ?
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Moist
Warm
Living
Defended by
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Mucus
Sloughing
Chemicals
Peristalsis/cilia
Normal flora
Immune cells/molecules - -magainins
Other chemical defenses
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Complement
Phagocytes - neutrophil(PMN) monocyte
and macrophage (fixed or wandering)
Contain granules
(lysosomes for
digesting)
• chemotaxis,
• engulfment(phagos
ome);
• fusion(phagolysoso
me);
• Degranulation
Activation of Compliment by Antgens
“Classical pathway”
Inflammation
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Localizes infection and prevents spread.
Redness, swelling, pain and heat are due to vascular
permeability which allows for phagocytic chemotaxis.