Bacterial Pathogenesis Pin Ling ( 凌 斌 ), Ph.D. Department of Microbiology & Immunology, NCKU ext...
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Transcript of Bacterial Pathogenesis Pin Ling ( 凌 斌 ), Ph.D. Department of Microbiology & Immunology, NCKU ext...
Bacterial Pathogenesis
• Pin Ling ( 凌 斌 ), Ph.D. Department of Microbiology & Immunology, NCKUext [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
: infection : shedding
The most frequent portals of entry- Mucus - Skin
Routes:
Ingestion, inhalation, traum
a, needles, catheters, arthr
opod bite, sexual transmiss
ion
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
Characteristics of Pathogenic Bacteria
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
ImmunopathogenesisToxins
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
Adherence of bacterium to epithelial or endothelial cell
s allow them to colonize the tissue.
Common adhesins: pili (fimbriae), slime, lipoteichoic ac
id, surface proteins or lectins.
Biofilm, formed on a surface by the bacteria that are bo
und together within a sticky web of polysaccharide, is a
special bacterial adaptation that facilitates colonization
on the surgical appliances (e.g., artificial valves or indw
elling catheters) and dental plaque. It can protect the b
acteria from host defenses and antibiotics.
Back
The bacteria may invade via the M cells
Back
M (Microfold) cells
Lipid A of lipopolysaccharide is responsible for endotoxin activity
Pathogenesis of sepsis (septicemia)
Endotoxin (LPS)-mediated toxicity
Fever,
leukopenia followed by leukocytosis,
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 gram-positive bacteria stimulate pyrogenic acute phase responses and produce endotoxin-like toxicity
Back
Endotoxin-mediated 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
The A-B toxins
Mode of action
Inhibition of protein synthesis
Hypersecretion
Inhibition of neurotransmitter release
A chain has the inhibitory activity against some vital function
B chain binds to a receptor and promotes entry of the A chain
In many cases the toxin gene is encoded on a plasmid or a lysogenic phage
Back
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
Microbial defenses against host immunologic clearance
Mechanisms for escaping phagocytic clearance and intracellular survival
Mechanisms for escaping phagocytic clearance and intracellular survival
Mechanisms for escaping phagocytic clearance and intracellular survival
Environmental factors often control the expression of t
he virulence genes.
Common factors: temperature, iron availability, osmolar
ity, growth phase, pH, specific ions, specific nutrient fa
ctors, bacterial cell-density, interaction with host cells.
Regulation of bacterial virulence factors
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