O'Donnell Bacterial Pathogenesis

Pathogenicity

The ability of a microbe to cause disease by overcoming host defenses

Virulence

The degree to which a microbe is pathogenic

Type of relationship between normal flora and host

Commensal relationship (one benefits, one is unaffected)

Opportunistic Infections

Take advantage of special situations to grow

• Ex. Mycobacterium avium is seen in AIDS patients. It does not usually do much unless patient is immunocompromised

Nosocomial Infections

Acquired in hospitals

Most common type = UTIs (E. coli)

Associated with high levels of antibiotic resistance

Pathogenic Infection

Interaction between a specific pathogen and the host leads to disease

• Bacteria damage host tissues

  • Toxins produced by bacteria

• Immunopathology

Immunopathology

Immune system damages the host while trying to attack the pathogen

Outbreak

Local spread of infectious disease

Epidemic

Regional/national spread of infectious disease

Pandemic

Widespread (international) spread of infectious disease

Stages of pathogenesis

1. Exposure

2. Adhesion

3. Invasion

4. Infection

Adhesion

Microbes attach to the host at a portal of entry using special cell surface molecules

• Often a mucosal surface (GI tract, respiratory tract)

Pili allow for initial contact with host cell

Adhesins allow for attachment to the host

What makes adhesion a specific process?

Pili typically attach first. The type of pili can determine where the bacteria can attach

Adhesins are proteins that bind to a receptor on the host cell. The type of adhesin determines the type of cell the bacteria can bind to

How do different types of pili affect E. coli?

Common E. coli

• Pili only bind to the large intestine

Pathogenic E. coli

• Over 20 different kinds of pili

• Some pili bind to small intestine → causes diarrhea

• Some pili bind to the urinary tract → causes UTIs

• Genes for different pili are passed on plasmids

How does the type of adhesin affect Streptococcus pyogenes?

Adhesin is F-protein

F-protein binds to fibronectin, a protein expressed on the surface of epithelial cells in the throat → adhesion to specifically those cells → infection

Once bacteria have attached to a cell they can:

• Colonize that area only

• Spread to a different area of the body

• Invade or enter the host cell to which it is attached

  • For intracellular bacteria specifically

What happens after H. pylori attaches to cells in the stomach?

Destroys the protective mucus layer in the stomach to reach the stomach epithelium. Then, both stomach acid and the bacteria destroy the stomach lining

Once safely inside the cell, intracellular bacteria _____

Multiply then exit the cell

• This kills the cell

Extracellular bacteria

Remain external to the cell

Can form communities

• Biofilms

  • Groups of bacteria build a slime layer around themselves

  • Macrophages cannot get through the biofilm

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

Endotoxins and exotoxins

Toxins

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

Endotoxins

Lipopolysaccharide (LPS) found in the outer membrane of gram negative bacteria

• Only exotoxin

Released when cells divide or die

Produces general inflammation

Exotoxins

Proteins produces by gram positive and gram negative bacteria

Produced and released as part of metabolism

Produce specific damage to host cells

Can act locally or be carried throughout the body

Where are genes for exotoxins usually found?

Plasmids

Four main types of exotoxins

1. A-B exotoxins

2. Membrane-Active exotoxins

3. Superantigens

4. Exoenzymes

A-B Exotoxins

Enzymes that inhibit cell functions

Includes most exotoxins

Two distinct domains

• A - “Active”

  • Does the damage

• B - “Binding”

  • Binds to the host cell

Classified by the host cell that is damaged

• Neurotoxins, enterotoxins, cytotoxins

Neurotoxins

Damage the nervous system

Enterotoxins

Damage the intestine, causing diarrhea and dehydration

Can either prevent the uptake of water from the digestive tract or cause cells to release iron and water

Cytotoxins

Damage a variety of cell types

Botulism toxin

Neurotoxin that prevents the release of acetylcholine from motor neurons, stopping muscle contraction → leads to flaccid paralysis

Tetanus toxin

Neurotoxin that prevents the release of glycine and GABA from inhibitory neurons, preventing the relaxation of muscles → leads to rigid paralysis (“lockjaw”)

Cholera toxin

Induces severe dehydration and death by forcing cells to secrete water

Membrane-active exotoxins

Kill the host cells by damaging the plasma membrane

• Pore-forming exotoxins

• Phospholipases

Pore-forming exotoxins

Make a hole in the membrane, allowing influx of water into the cell

• Causes cell lysis

• Associated with severe food poisoning

Phospholipases

Cleave the lipids in the membrane

• Causes destabilization of the host membrane and cell death

Superantigen exotoxins

Activate 20-30% of your T cells (conventional antigens only activate 0.01-0.1%), which can cause toxic shock syndrome

Exoenzymes

Breakdown collagen and connective tissue

• Allows for spread of the bacteria from the original site of infection

Why do bacteria have toxins?

Bacteria want to change the environment to their favor

• Ex. Anaerobic bacteria want to create an environment without oxygen

Clostridium perfringens

Can cause gas gangrene

• Usually part of an injury

• Releases a phospholipase

• Destroys blood vessels

  • Prevents immune cells from reaching the bacteria

  • Disrupts the delivery of oxygen

  • Can spread with the toxin from that point and destroy the limb

Other than directly damaging the host, how else can bacteria increase pathogenicity?

By evading the immune response

Phagocytosis

Process by which immune cells engulf and digest bacteria

What happens after a bacteria is internalized by a phagocyte?

Bacteria is placed in a phagosome, which is fused with a lysosome to make a phagolysosome. The bacteria is then degraded and exocytosed

Two ways to tag a bacteria for phagocytosis

Complement protein - a non-specific tag

• Complement (C3) is always present in your serum and can attach to many different microbes and foreign proteins

Antibodies/immunoglobulins - a specific tag

• Made by B-cells

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

How does complement allow a macrophage to phagocytose bacteria?

Complement (C3b) is cleaved when it comes into contact with bacteria surface → deposition of C3b on bacteria surface → CR1 on macrophage binds C3b on bacterium → phagocytosis

How do antibodies allow a macrophage to phagocytose bacteria?

Antibody coated bacteria bind the Fc receptors on the surface of phagocytes

Role of bacterial capsules

Make bacteria more invasive

• Common in bacteria that cause pneumonia and meningitis

How can bacteria avoid complement?

Bacteria can form capsules and biofilms

• Interferes with the ability of phagocytes to recognize or adhere to the bacteria

Capsules bind to Factor H in our Serum

• We naturally make Factor H → degrades complement proteins in the area

• Protects bacteria from complement binding

How can bacteria interfere with antibodies?

IgG proteases

• Cleave the “hinge” region, separating the variable region and the Fc region

IgG binding proteins

• Bind to the Fc region of the antibody, preventing binding to the Fc receptor on the phagocyte

Antigenic variation

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

How does Neisseria gonorrhoeae use antigenic variation?

Continually alters the gene sequence of its pili to evade the immune response