Microbial Mechanisms of Pathogenicity: Study Notes

Microbial Mechanisms of Pathogenicity

Introduction

Microbial pathogenesis refers to the process by which microorganisms cause disease in a host. Understanding the mechanisms of pathogenicity is essential for identifying how infections occur, how diseases develop, and how the body responds to microbial threats. This section covers the steps of infection, portals of entry, definitions of key terms, and the factors that contribute to a microbe's ability to cause disease.

How Microorganisms Enter a Host

Portals of Entry

• Skin: Pathogens may enter through natural openings (hair follicles, sweat glands, pores), or via cuts, abrasions, bites, scrapes, stab wounds, or surgery. Some organisms can burrow into or digest the outer skin layer (e.g., Schistosoma species).

• Mucous Membranes: These epithelial layers line body cavities open to the environment and secrete mucus, which acts as a barrier to pathogens. The respiratory tract is the most common site of entry, followed by the gastrointestinal tract (which requires survival of acidic stomach pH), and the conjunctiva (eyes).

• Placenta: Some pathogens can cross the placental barrier to infect the fetus.

• Parenteral Route: Pathogens are introduced directly into tissues beneath the skin or mucous membranes, bypassing natural barriers (e.g., via punctures, cuts, needles, or insect bites).

Key Point: The route of entry can influence the outcome and severity of infection.

The Infection Process

Stages of Infection

1. Exposure: Contact with the pathogen.

2. Adherence: Pathogen attaches to host tissues.

3. Colonization: Pathogen establishes itself, invades tissues, and accesses nutrients.

4. Multiplication: Pathogen replicates within the host.

After colonization, the disease process may begin, involving toxicity (toxin secretion) and invasiveness (growth and spread within tissues).

Contamination, Infection, and Disease

Definitions

• Contamination: Presence of microbes in or on the body. These may become part of the resident or transient microbiota.

• Infection: Pathogen overcomes host defenses and colonizes the host. Infection may or may not result in disease.

• Disease: Infection leads to altered normal body functions.

Clinical Terms

• Symptoms: Subjective characteristics felt by the patient (e.g., pain, fatigue).

• Signs: Objective, observable effects (e.g., fever, rash).

• Syndrome: Group of symptoms and signs that characterize a disease (e.g., AIDS).

• Asymptomatic (Subclinical): Infection without noticeable symptoms, but signs may be present (e.g., increased WBC count).

Example: If John handled Salmonella-contaminated spinach and washed his hands, removing all bacteria, he was contaminated but not infected or diseased, as the bacteria did not colonize or cause symptoms.

Pathogenicity, Virulence, and Related Concepts

• Pathogenicity: Ability of a microorganism to cause disease.

• Virulence: Degree of pathogenicity; how severe the disease is.

• Attenuation: Decrease or loss of virulence.

• Bacterial Load: Number of pathogens per gram of tissue.

• Bacteremia: Presence of bacteria in the blood; parasitemia and viremia refer to parasites and viruses, respectively.

• ID50: Infectious dose required to infect 50% of a population.

• LD50: Lethal dose required to kill 50% of a population.

Formulas:

• ID50 and LD50 are determined experimentally by exposing groups to varying doses and recording infection or death rates.

How Pathogens Circumvent Host Defenses

Microbial Adherence

• Adhesins: Molecules on the pathogen surface that bind to specific host cell receptors (often glycoproteins or lipoproteins).

• Host Cell Receptors: Usually glycoproteins (proteins with carbohydrate groups attached) or lipoproteins (proteins with lipid groups attached); may be tissue-specific.

• Adherence Structures:

  • Capsule: e.g., Bacillus anthracis, Streptococcus pneumoniae (major virulence factor).

  • Pili: e.g., Neisseria gonorrhoeae.

  • Fimbriae: e.g., Escherichia coli.

  • Flagella: e.g., Salmonella enterica.

Example: The Griffith experiment (1928) showed that the capsule of S. pneumoniae is essential for virulence, as only encapsulated strains caused disease in mice.

Microbial Colonization and Invasion

• Host defenses (immune system) act to prevent colonization.

• Pathogens use various strategies to colonize and invade tissues.

Dental Cavities Example

• Streptococcus sobrinus: Capsule contains adhesins for salivary glycoproteins.

• Streptococcus mutans: Secretes dextran (a polysaccharide) that helps adherence to teeth and gums; ferments sugars to lactic acid, which destroys enamel and leads to cavities.

Additional info: Dextran forms a sticky matrix that traps bacteria on tooth surfaces, facilitating plaque formation and acid production.

Virulence Factors

Definition

Virulence factors are traits of a pathogen that enable entry, adherence, access to nutrients, and evasion of the immune system. The combination of these factors determines the overall virulence of a microorganism.

• Adhesion factors

• Extracellular enzymes

• Toxins

• Antiphagocytic factors

Extracellular Enzymes

• Hyaluronidase: Breaks down hyaluronic acid (extracellular matrix component), allowing deeper tissue invasion (e.g., by streptococci, clostridia).

• Collagenase: Degrades collagen (extracellular matrix), facilitating spread (e.g., by clostridia).

• Coagulase: Induces blood clotting (fibrinogen to fibrin), helping pathogens evade immune cells (e.g., Staphylococcus aureus).

• Streptokinase/Staphylokinase: Dissolve fibrin clots, allowing pathogen spread (e.g., Streptococcus pyogenes, Staphylococcus aureus).

• IgA Proteases: Inactivate IgA antibodies, which protect mucosal surfaces (e.g., Neisseria species).

Additional info: The extracellular matrix is a network of proteins and polysaccharides that provides structural support to tissues. Degrading it allows pathogens to penetrate and disseminate.

Toxins and Pathogenicity

Types of Toxins

• Toxins: Poisonous substances produced by microbes; can cause fever, cardiovascular issues, diarrhea, and shock.

• Toxigenicity: Ability to produce toxins.

• Toxemia: Presence of toxins in the blood.

• Intoxication: Disease caused by toxin without microbial growth in the host.

AB Toxins

• Composed of two subunits:

  • B subunit: Binds to host cell receptor.

  • A subunit: Enters cell and disrupts cellular function.

Toxin	Exposure Route	Mechanism	Effect
Diphtheria exotoxin	Infection	Inhibits protein synthesis	Cell death
Botulinum toxin	Food poisoning, wound infection	Blocks acetylcholine release	Flaccid paralysis
Cholera enterotoxin	Contaminated food/water	Activates adenylate cyclase, increases cAMP	Massive diarrhea, dehydration

General Mechanism of AB Toxins:

$\text{B subunit binds to host cell receptor} \rightarrow \text{A subunit enters cell} \rightarrow \text{A subunit disrupts cellular process}$

Cytolytic Toxins

• Cause cell lysis (destruction of host cells).

• Hemolysins: Detected by their ability to lyse red blood cells in lab assays.

• Lecithinases/Phospholipases: Cleave phospholipids in cell membranes (e.g., Clostridium perfringens).

• Staphylococcal alpha-toxin: Forms pores in host cell membranes (Staphylococcus aureus).

Comparison: Phospholipases degrade membrane lipids, while alpha-toxin forms pores, both leading to cell death.

Superantigen Exotoxins

• Trigger excessive, non-specific activation of T-cells by binding directly to T-cell receptors (TCR).

• Cause strong inflammation, hypotension, fever, diarrhea, and vomiting.

• Examples: Staphylococcus aureus (food poisoning, TSS), Streptococcus pyogenes (systemic infections).

Endotoxins

• Component of Gram-negative bacterial outer membrane (lipopolysaccharide, LPS).

• Toxic portion: Lipid A, which activates immune cells via TLR4.

• Causes systemic inflammation, fever, diarrhea, increased heart rate.

• Detected by Limulus amoebocyte assay (LAL), using horseshoe crab blood.

Exotoxins, Antitoxins, and Toxoids

• Exotoxins: Proteins secreted by bacteria; soluble, destroy host cells, inhibit metabolism.

• Antitoxins: Antibodies that neutralize specific exotoxins.

• Toxoids: Inactivated exotoxins used in vaccines (e.g., diphtheria, tetanus vaccines).

Siderophores

• Molecules secreted by pathogens to bind and acquire iron, an essential nutrient for microbial growth.

Pathogenic Properties of Fungi, Protozoa, Helminths, and Algae

• Plasmodium (malaria): Characteristic sign is periodic fever (paroxysms) due to synchronous lysis of red blood cells.

• Toxoplasma (toxoplasmosis): Can alter host behavior and cause neurological symptoms; often transmitted via cat feces or undercooked meat.

Portals of Exit

• Pathogens most often exit the host via the same routes as entry: respiratory tract (coughing, sneezing), gastrointestinal tract (feces, saliva), urogenital tract, skin, and blood (e.g., via insect vectors or needles).