Transcript Bacterial Pathogenesis

Bacterial Pathogenesis
• Pin Ling (凌 斌), Ph.D.
Department of Microbiology & Immunology, NCKU
ext 5632
[email protected]
• References:
1. Chapter 19 in Medical Microbiology (Murray, P. R.
et al; 5th edition)
2. 醫用微生物學 (王聖予 等編譯, 4th edition)
Outline
Bacterial Pathogenesis
• Introduction
• Host Susceptibility
• Pathogenic Mechanisms
• Virulence Factors
Introduction of Bacterial Pathogenesis
1.
Infection: growth and multiplication of a microbe in or
on the body with or without the production of disease.
2.
The capacity of a bacterium to cause disease reflects
its relative “Pathogenicity.”
3.
Virulence is the measure of the pathogenicity of a
microorganism.
4.
Pathogenesis refers both to the mechanism of
infection and to the mechanism by which disease
develops.
Host Susceptibility
1.
Susceptibility to bacterial infections
=> Host Defenses vs Bacterial Virulence
2.
Host Defenses:
- Barriers (skin & mucus) – first line
- Innate Immune Responses (complement, macrophages &
cytokines) – the early stage
- Adaptive Immune Responses (Ag-specific B & T cells) – the
later stage
3.
Host defenses can be comprised by destructing barriers or
defective immune response.
e.x. Cystic Fibrosis => poor ciliary function => NOT clear mucus
efficiently from the respiratory tract => Pseudomonas aeruginosa
=> serious respiratory distress.
Strict pathogens
are more virulent and can
cause diseases in a normal
person.
Opportunistic pathogens
are typically members of
normal flora and cause
diseases when they are
introduced into
unprotected sites; usually
occur in people with
underlying conditions.
Entry into the human body
The most frequent portals
of entry- Mucus
- Skin
Routes:
Ingestion, inhalation,
trauma, needles, catheters,
arthropod bite, sexual
transmission
: infection
: shedding
Characteristics of Pathogenic
Bacteria
1. Transmissibility
2. Adherence to host cells
3. Invasion of host cells and tissue
4. Evasion of the host immune system
5. Toxigenicity
A bacterium may cause diseases by
1. Destroying tissue (invasiveness)
2. Producing toxins (toxigenicity)
3. Stimulating overwhelming host immune
responses
Pathological Mechanisms of Bacterial
Infections
1.
Bacteria-mediated
Pathogenesis
2.
Host-mediated
Pathogenesis
3.
Bacterial virulence
factors
=> bacterial factors
causing diseases
Adopted from Samuel Baron “Medical Microbiology”
Bacterial Virulence Mechanisms
Bacterial virulence factors
Adhesins
Pili (fimbriae)
Nonfimbrial adhesins
Invasion of host cells
Tissue damage
Growth byproducts
Tissue-degrading enzymes
Immunopathogenesis
Toxins
Exotoxins (cytolytic enzymes
and A-B toxins); enterotoxins;
superantigens;
endotoxin and other cell wall
components
Antiphagocytic factors
Intracellular survival
Antigenic heterogeneity
Antigenic variation
Phase variation
Iron acquisition
Siderophores
Receptors for
iron-containing molecules
Resistance to antibiotics
Adhesion
Back
Adherence of bacterium to epithelial or endothelial
cells allow them to colonize the tissue.
Common adhesins: pili (fimbriae), slime, lipoteichoic
acid, surface proteins or lectins.
Biofilm, formed on a surface by the bacteria that are
bound together within a sticky web of polysaccharide,
is a special bacterial adaptation that facilitates
colonization on the surgical appliances (e.g., artificial
valves or indwelling catheters) and dental plaque. It can
protect the bacteria from host defenses and antibiotics.
The bacteria may invade via the M cells
M (Microfold) cells
Back
Endotoxin (LPS)-mediated toxicity
Lipid A of
lipopolysaccharide is
responsible for
endotoxin activity
Pathogenesis of
sepsis (septicemia)
Endotoxin-mediated toxicity
Fever,
Leukocytosis => leukopenia
activation of complement, thrombocytopenia,
disseminated intravasacular coagulation,
decreased peripheral circulation and perfusion to
major organs (multiple organ system failure),
Shock and death.
Peptidoglycan, teichoic and lipoteichoic acids of grampositive bacteria stimulate pyrogenic acute phase
responses and produce endotoxin-like toxicity
Back
Superantigen-mediated toxicity
1. Bind to TCR and activate T
cells w/o Ag
2. Autoimmune-like responses
3. S. aureus =>Toxic shock
syndrome toxin
S. pyogenes=> Erythrogenic
toxin A orC
Back
The A-B toxins
A chain has the inhibitory activity against some vital function
B chain binds to a receptor and promotes entry of the A chain
Back
Mode of action
Inhibition of
protein synthesis
Hypersecretion
Inhibition of
neurotransmitter
release
In many cases
the toxin gene is
encoded on a
plasmid or a
lysogenic phage
Microbial defenses against host immunologic clearance
Encapsulation (Inhibition of phagocytosis and serum
bactericidal effect)
Antigenic mimicry
Antigenic masking
Antigenic or phase variation
Intracellular multiplication
Escape phagosome
Inhibition of phagolysosome fusion
Resistance to lysosomal enzymes
Production of anti-immunoglobulin protease
Inhibition of chemotaxis
Destruction of phagocytes
Mechanisms for escaping
phagocytic clearance and
intracellular survival
Mechanisms for escaping
phagocytic clearance and
intracellular survival
Mechanisms for escaping
phagocytic clearance and
intracellular survival
Regulation of bacterial virulence factors
Environmental factors often control the expression of
the virulence genes.
Common factors: temperature, iron availability,
osmolarity, growth phase, pH, specific ions, specific
nutrient factors, bacterial cell-density, interaction with
host cells.
SUMMARY
1. Host Defenses:
- Barriers (skin & mucus) – first line
- Innate Immune Responses (complement, macrophages &
cytokines) – the early stage
- Adaptive Immune Responses (Ag-specific B & T cells) – the
later stage
2. Susceptibility to bacterial infections depends on the balance
between host defenses and bacterial virulence.
3. Pathogenic mechanisms of bacterial infections include
•
Bacteria-mediated Pathogenesis
•
Host-mediated Pathogenesis
Mechanisms of acquiring bacterial
virulence genes