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Bacterial Pathogene sis Pin Ling ( 凌 凌 ), Ph.D. Department of Microbiology & Immunology, NCKU ext 5632 [email protected] • References: 1. Chapter 19 in Medical Microbiology (Murray, P. R. et al; 5 th edition) 2. 凌凌凌凌凌凌 ( 凌凌凌 凌凌凌 , 4th edition)

Bacterial Pathogenesis Pin Ling ( 凌 斌 ), Ph.D. Department of Microbiology & Immunology, NCKU ext 5632 [email protected] References: 1. Chapter 19

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Page 1: Bacterial Pathogenesis Pin Ling ( 凌 斌 ), Ph.D. Department of Microbiology & Immunology, NCKU ext 5632 lingpin@mail.ncku.edu.tw References: 1. Chapter 19

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)

Page 2: Bacterial Pathogenesis Pin Ling ( 凌 斌 ), Ph.D. Department of Microbiology & Immunology, NCKU ext 5632 lingpin@mail.ncku.edu.tw References: 1. Chapter 19

Outline

Bacterial Pathogenesis

• Introduction

• Host Susceptibility

• Pathogenic Mechanisms

• Virulence Factors

Page 3: Bacterial Pathogenesis Pin Ling ( 凌 斌 ), Ph.D. Department of Microbiology & Immunology, NCKU ext 5632 lingpin@mail.ncku.edu.tw References: 1. Chapter 19

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.

Page 4: Bacterial Pathogenesis Pin Ling ( 凌 斌 ), Ph.D. Department of Microbiology & Immunology, NCKU ext 5632 lingpin@mail.ncku.edu.tw References: 1. Chapter 19

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.

Page 5: Bacterial Pathogenesis Pin Ling ( 凌 斌 ), Ph.D. Department of Microbiology & Immunology, NCKU ext 5632 lingpin@mail.ncku.edu.tw References: 1. Chapter 19

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.

Page 6: Bacterial Pathogenesis Pin Ling ( 凌 斌 ), Ph.D. Department of Microbiology & Immunology, NCKU ext 5632 lingpin@mail.ncku.edu.tw References: 1. Chapter 19

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

Page 7: Bacterial Pathogenesis Pin Ling ( 凌 斌 ), Ph.D. Department of Microbiology & Immunology, NCKU ext 5632 lingpin@mail.ncku.edu.tw References: 1. Chapter 19

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

Page 8: Bacterial Pathogenesis Pin Ling ( 凌 斌 ), Ph.D. Department of Microbiology & Immunology, NCKU ext 5632 lingpin@mail.ncku.edu.tw References: 1. Chapter 19

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”

Page 9: Bacterial Pathogenesis Pin Ling ( 凌 斌 ), Ph.D. Department of Microbiology & Immunology, NCKU ext 5632 lingpin@mail.ncku.edu.tw References: 1. Chapter 19

Bacterial Virulence Mechanisms

Page 10: Bacterial Pathogenesis Pin Ling ( 凌 斌 ), Ph.D. Department of Microbiology & Immunology, NCKU ext 5632 lingpin@mail.ncku.edu.tw References: 1. Chapter 19

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

Page 11: Bacterial Pathogenesis Pin Ling ( 凌 斌 ), Ph.D. Department of Microbiology & Immunology, NCKU ext 5632 lingpin@mail.ncku.edu.tw References: 1. Chapter 19

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

Page 12: Bacterial Pathogenesis Pin Ling ( 凌 斌 ), Ph.D. Department of Microbiology & Immunology, NCKU ext 5632 lingpin@mail.ncku.edu.tw References: 1. Chapter 19

The bacteria may invade via the M cells

Back

M (Microfold) cells

Page 13: Bacterial Pathogenesis Pin Ling ( 凌 斌 ), Ph.D. Department of Microbiology & Immunology, NCKU ext 5632 lingpin@mail.ncku.edu.tw References: 1. Chapter 19

Lipid A of lipopolysaccharide is responsible for endotoxin activity

Pathogenesis of sepsis (septicemia)

Endotoxin (LPS)-mediated toxicity

Page 14: Bacterial Pathogenesis Pin Ling ( 凌 斌 ), Ph.D. Department of Microbiology & Immunology, NCKU ext 5632 lingpin@mail.ncku.edu.tw References: 1. Chapter 19

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

Page 15: Bacterial Pathogenesis Pin Ling ( 凌 斌 ), Ph.D. Department of Microbiology & Immunology, NCKU ext 5632 lingpin@mail.ncku.edu.tw References: 1. Chapter 19

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

Page 16: Bacterial Pathogenesis Pin Ling ( 凌 斌 ), Ph.D. Department of Microbiology & Immunology, NCKU ext 5632 lingpin@mail.ncku.edu.tw References: 1. Chapter 19

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

Page 17: Bacterial Pathogenesis Pin Ling ( 凌 斌 ), Ph.D. Department of Microbiology & Immunology, NCKU ext 5632 lingpin@mail.ncku.edu.tw References: 1. Chapter 19

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

Page 18: Bacterial Pathogenesis Pin Ling ( 凌 斌 ), Ph.D. Department of Microbiology & Immunology, NCKU ext 5632 lingpin@mail.ncku.edu.tw References: 1. Chapter 19

Mechanisms for escaping phagocytic clearance and intracellular survival

Page 19: Bacterial Pathogenesis Pin Ling ( 凌 斌 ), Ph.D. Department of Microbiology & Immunology, NCKU ext 5632 lingpin@mail.ncku.edu.tw References: 1. Chapter 19

Mechanisms for escaping phagocytic clearance and intracellular survival

Page 20: Bacterial Pathogenesis Pin Ling ( 凌 斌 ), Ph.D. Department of Microbiology & Immunology, NCKU ext 5632 lingpin@mail.ncku.edu.tw References: 1. Chapter 19

Mechanisms for escaping phagocytic clearance and intracellular survival

Page 21: Bacterial Pathogenesis Pin Ling ( 凌 斌 ), Ph.D. Department of Microbiology & Immunology, NCKU ext 5632 lingpin@mail.ncku.edu.tw References: 1. Chapter 19

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

Page 22: Bacterial Pathogenesis Pin Ling ( 凌 斌 ), Ph.D. Department of Microbiology & Immunology, NCKU ext 5632 lingpin@mail.ncku.edu.tw References: 1. Chapter 19

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

Page 23: Bacterial Pathogenesis Pin Ling ( 凌 斌 ), Ph.D. Department of Microbiology & Immunology, NCKU ext 5632 lingpin@mail.ncku.edu.tw References: 1. Chapter 19
Page 24: Bacterial Pathogenesis Pin Ling ( 凌 斌 ), Ph.D. Department of Microbiology & Immunology, NCKU ext 5632 lingpin@mail.ncku.edu.tw References: 1. Chapter 19

Mechanisms of acquiring bacterial

virulence genes