Topic VI: Bacterial Pathogenesis

What are the stages of a pathogenic infection?

• Exposure

• Adhesion- role of pili & other surface proteins

• Invasion/infection

  • Extracellular vs. intracellular bacteria

How do bacteria cause disease?

• Immune evasion

  • Interference w/ phagocytosis

  • Antigenic variation

• Endotoxins & exotoxins

  • AB exotoxins

  • Membrane-active exotoxins

  • Superantigens

What is pathogenicity?

Ability of a microbe to cause disease by overcoming host defenses

What is virulence?

Degree to which a microbe is pathogenic

What is normal flora (microbiome)?

Commensal relationship w/ host

What are opportunistic infections?

• Take advantage of special situation to grow

  • Mycobacterium avium: seen in AIDS patients

What are nosocomial infections?

Acquired in hospitals

• Also called hospital-acquired infections (HAI)

• Around 1.7 million cases per year in US

• Most common: UTIs (E. Coli)

What are pathogenic infections?

Interaction b/w a specific pathogen & host leads to disease

• Bacteria damage host tissue

  • Toxins produced by bacteria

  • Damage to host cells as bacteria replicate

• Immunopathology

  • Immune system damages host while trying to attack bacteria

What are the different terms to describe when pathogens happen beyond the normal rate?

• Outbreak: local

• Epidemic: regional/national

• Pandemic: widespread (international)

What are the stages of pathogenesis?

1. Exposure

2. Adhesion

3. Invasion/infection

What do infections begin w/?

Exposure & adhesion

How do microbes attach?

Attach to host at a portal of entry using special cell surface molecules

• Very often a mucosal surface (GI tract, respiratory tract)

What is adhesion?

Specific process

• Pili allow for initial contact w/ host cell

• Other surface proteins, called “adhesions”, allow for attachment to host

What does a bacteria’s pili & adhesions determine?

Type of host cells/tissues that it can infect

What does type of pili determine?

Where bacteria can attach

What are the aspects of common E. Coli?

• Have pili that only bind to cells in large intestine

• Typically just part of normal flora

What are the aspects of pathogenic E. Coli?

• Over 20 different kinds of pili have been identified

• Some pili can bind to small intestine, causing diarrhea & food poisoning, or to urinary tract, causing UTIs

• Genes for different pili are passed on plasmids

What is invasion?

Once bacteria have attached to cell, they might:

• Colonize that area only

• Spread to a different area of body

• Invade (or enter) host cells to which it is attached

  • For intracellular bacteria specifically

What is invasion w/ H. Pylori?

• Destroys protective mucus layer in stomach to reach stomach epithelium

• Then, both stomach acid & bacteria destroy stomach lining

How do intracellular bacteria establish an infection?

Once safely inside cell, intracellular bacteria multiply & then exit cell

• This typically kills host cell

How do extracellular bacteria establish an infection?

• Many bacteria remain external to cell

  • Extracellular bacteria

• Extracellular bacteria can form communities

  • Biofilms- groups of bacteria build a slime layer around themselves

    • Macrophages cannot get through biofilm

    • Difficult to penetrate w/ antibiotics

What is phagocytosis?

Process by which our immune cells (macrophages, neutrophils) engulf & digest (breakdown) bacteria

How do immune cells know what to phagocytose?

• Bacteria must be “tagged” by immune proteins

  • These proteins allow phagocytic cell to recognize (& bind to) bacteria

What are the 2 ways to “tag” bacteria?

1. Complement proteins- a non-specific tag

• Complement (C3) is always present in your serum

• Can attach to many different microbes & foreign proteins

2. Antibodies or immunoglobulins- a specific tag

• Made by B-cells

• Can be made as different types (IgG, IgA, etc.)

How can some bacteria avoid complement?

• Some bacteria can form capsules (1 cell) & biofilms (community of cells)

  • Interferes w/ ability of immune cells to recognize & ingest bacteria

    • Capsule formation is common for bacteria that cause pneumonia & meningitis

    • Capsules can make bacteria more invasive

How do capsules & biofilms protect bacteria?

• Capsules bind to Factor H in our serum

  • We make Factor H naturally!

  • Factor H degrades complement proteins in area

• When bacteria gather Factor H from our serum, it protects bacteria from complement binding

How can bacteria interfere w/ antibodies?

Subverting IgG

• IgG proteases

  • Cleave the “hinge” region

  • Separates variable region & Fc region

• IgG binding proteins

  • Bind to Fc region of antibody

  • Prevent binding to “Fc receptor” on phagocytes, so immune cells cannot grab bacteria

Associated w/ increased virulence

What is antigenic variation?

• Process by which pathogens display new surface antigens that are not recognized by antigens elicited in earlier infection

  • Neisseria gonorrhoeae

    • N. Gonorrhoeae continually alters sequence of its pili

• Many bacteria, viruses, & parasites can do this

Once an infection is established, how is the host damaged?

Endotoxins & exotoxins

What are toxins?

Biological poisons that improve pathogens’ ability to invade their host & cause disease

What are endotoxins?

• Lipopolysaccharide (LPS) found the outer membrane of Gm- bacteria

• Released when cells divide or die

• Produces general inflammation

What are exotoxins?

• Proteins produced by Gm+ & Gm- bacteria

• Produced & released as part of metabolism

• Produce specific damage to host cells

Where are exotoxins?

• Can act locally, or be carried throughout the body

• Genes for exotoxins are usually on plasmids

What are the 4 main types of exotoxins?

1. A-B exotoxins

• Enzymes that inhibit cell functions

2. Membrane-active exotoxins

• Cause cell lysis

3. Superantigens

• Overstimulate immune system

4. Exoenzymes

• Breakdown collagen & connective tissue

  • Allow for spread of bacteria from original site of infection

What are A-B exotoxins?

• Most common

• Have 2 domains:

  • A= “active” → enzyme

    • Does the damage

  • B= “binding”

    • Binds to host cell

• Classified by host cell that is damaged

  • Neurotoxins- damage NS

  • Enterotoxins- damage intestine

  • Cytotoxic- damage variety of cell types

What is botulism toxin?

• Clostridium botulinum

• Target motor neurons

• Causes flaccid paralysis

What is tetanus toxin?

• Clostridium tetani

• Targets inhibitory neurons

• Causes rigid paralysis

What is cholera toxin?

• Vibrio cholerae

• Targets gut epithelium

• Causes diarrhea/dysentery

What are the enterotoxins of A-B exotoxins?

• Cause diarrhea & dehydration

• Can either prevent uptake of water from digestive tract or cause cells to release iron & water

  • Cholera toxin- induces severe dehydration & cell death by forcing cells in intestine to secrete water

What are membrane-active exotoxins?

Lead to disruption of plasma membrane & cell death

• Pore-forming exotoxins- allow influx of water into cell

  • Causes cells to lyse (explode)

  • Associated w/ severe food poisoning

• Phospholipases- cleave lipids in membrane

  • Causes destabilization of host membrane & cell death

What are superantigen exotoxins?

Life-threatening inflammation

• Toxic-shock syndrome

• Sepsis

Why would bacteria have toxins?

Would want to change environment to their favor

What does Clostridium perfringens do?

Causes gas gangrene

• Usually results from deep wound or injury that breaks skin

• Releases a phospholipase that destroys blood vessels

  • Prevents immune cells from reaching bacteria

  • Disrupts delivery of oxygen to site of infection

  • Exotoxin (& bacteria) spread from point & destroy the limb

What is the purpose of some exotoxins still?

Unclear

• Tetanus toxin