Microbial Mechanisms of Pathogenicity: Chapter 15 Study Notes

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Microbial Mechanisms of Pathogenicity

Introduction

This chapter explores how microorganisms cause disease, focusing on the mechanisms by which pathogens invade hosts, evade defenses, and produce damage. Understanding these processes is essential for microbiology students to grasp the basis of infectious diseases and host-pathogen interactions.

Pathogenicity and Virulence

Definitions and Concepts

Pathogenicity: The ability of a microorganism to cause disease in a host.
Virulence: The degree of pathogenicity; refers to the severity of disease caused by a pathogen.

Virulence	Pathogenicity
Quantitative; measures severity and amount of infection.	Qualitative; refers to the ability to cause disease.
Measured by infectious dose (ID50).	Measured by virulence factors that enable evasion of host defenses.

Portals of Entry

How Microorganisms Enter a Host

Mucous membranes: Includes respiratory tract, digestive canal, genital system, urinary system, and conjunctiva.
Skin: Unbroken skin is generally impenetrable; entry possible via hair follicles and sweat gland ducts.
Parenteral route: Direct deposition into tissues beneath skin or mucous membranes (e.g., punctures, injections, bites, cuts, wounds, surgery).
Most pathogens have a preferred portal of entry for optimal infection.

Numbers of Invading Microbes

ID50 and LD50

ID50: Infectious dose for 50% of a sample population; measures virulence.
LD50: Lethal dose for 50% of a sample population; measures potency of a toxin.

Portal of Entry	ID50 (Bacillus anthracis)
Skin	10–50 endospores
Inhalation	10,000–20,000 endospores
Ingestion	250,000–1,000,000 endospores

Toxin	LD50
Botulinum	0.03 ng/kg
Shiga toxin	250 ng/kg
Staphylococcal enterotoxin	1350 ng/kg

Adherence

Mechanisms of Attachment

Pathogens attach to host tissues via adhesins (ligands) that bind to specific receptors on host cells.
Glycocalyx: Example—Streptococcus mutans uses dextran to adhere to teeth.
Fimbriae: Example—Actinomyces adheres to glycocalyx of S. mutans.
Viral spikes: Example—SARS-CoV-2 spikes adhere to ACE2 receptor on host cells.

Capsules and Cell Wall Components

Evading Host Defenses

Capsules: Glycocalyx around the cell wall impairs phagocytosis. Examples: Streptococcus pneumoniae, Haemophilus influenzae, Bacillus anthracis, Yersinia pestis.
Cell wall components:
- M protein: Resists phagocytosis (Streptococcus pyogenes).
- Opa protein: Allows attachment to host cells (Neisseria gonorrhoeae).
- Waxy lipid (mycolic acid): Resists digestion by phagocytes (Mycobacterium tuberculosis).

Enzymes as Virulence Factors

Functions and Examples

Coagulases: Coagulate fibrinogen, forming fibrin clots.
Kinases: Digest fibrin clots.
Hyaluronidase: Digests hyaluronic acid, a polysaccharide that holds cells together.
Collagenase: Breaks down collagen.
IgA proteases: Destroy IgA antibodies.

Antigenic Variation

Evading Immune Response

Pathogens alter their surface antigens, rendering host antibodies ineffective.
Examples: Influenza virus, Neisseria gonorrhoeae, Trypanosoma brucei gambiense.

Penetration into the Host

Invasins and Survival Inside Phagocytes

Invasins: Surface proteins produced by bacteria that rearrange actin filaments, causing membrane ruffling and engulfment.
Survival inside phagocytes:
- Requirement for low pH in phagolysosome.
- Escape from phagosome before lysosomal fusion.
- Prevention of fusion of lysosome with phagosome.

Biofilms

Role in Pathogenicity

Biofilms resist antibiotics and disinfectants.
Involved in 65% of all infections.
Biofilm bacteria are more resistant to phagocytosis, shielded by extracellular polymeric substance (EPS).

Using the Host’s Nutrients: Siderophores

Iron Acquisition

Iron is essential for most pathogenic bacteria.
Siderophores: Proteins secreted by pathogens that bind iron more tightly than host iron-binding proteins.

Example: Enterobactin is a bacterial siderophore that chelates Fe3+ ions.

Direct Damage to Host Cells

Mechanisms

Disrupts host cell function.
Uses host cell nutrients.
Produces waste products.
Multiplies in host cells, causing ruptures.

Production of Toxins

Types and Effects

Toxins: Poisonous substances produced by microorganisms; cause fever, cardiovascular problems, diarrhea, and shock.
Toxigenicity: Ability to produce a toxin.
Toxemia: Presence of toxin in the host's blood.
Intoxications: Presence of toxin without microbial growth.

Exotoxins

Characteristics and Types

Proteins produced and secreted by bacteria; soluble in bodily fluids.
Destroy host cells and inhibit metabolic functions; highly specific and sometimes highly lethal.
Antitoxins: Antibodies against specific exotoxins.
Toxoids: Inactivated exotoxins used in vaccines.

Types of Exotoxins

A-B toxins: Contain an enzyme component (A part) and a binding component (B part). Example: Diphtheria toxin.
Genotoxins: Damage DNA, causing mutations and potentially cancer.
Membrane-disrupting toxins: Lyse host cells by disrupting plasma membranes. Examples: Leukocidins (kill leukocytes), Hemolysins (kill erythrocytes), Streptolysins (produced by streptococci).
Superantigens: Cause intense immune response due to cytokine release from T cells, leading to fever, nausea, vomiting, diarrhea, shock, and death.

Disease	Bacterium	Type of Exotoxin	Mechanism
Botulism	Clostridium botulinum	A-B	Neurotoxin; prevents transmission of nerve impulses, flaccid paralysis results.
Tetanus	C. tetani	A-B	Neurotoxin; blocks nerve impulses to muscle relaxation, results in uncontrollable muscle contractions.
Diphtheria	Corynebacterium diphtheriae	A-B	Cytotoxin; inhibits protein synthesis, especially in nerve, heart, and kidney.
Scalded skin syndrome	S. aureus	A-B	Exotoxin; causes skin layers to separate and slough off.
Cholera	V. cholerae	A-B	Enterotoxin; causes secretion of large amounts of fluids and electrolytes that result in diarrhea.
Traveler's diarrhea	Enterotoxigenic E. coli and Shigella spp.	Enterotoxin	Enterotoxin; causes secretion of large amounts of fluids and electrolytes that result in diarrhea.
Anthrax	Bacillus anthracis	A-B	Two components enter the cell via the same receptor; the A-B exotoxin causes shock and reduces the immune response.

Disease	Bacterium	Type of Exotoxin	Mechanism
Gastric cancer	Helicobacter spp.	A-B toxin	Genotoxin; causes breaks in DNA.
Colorectal cancer	E. coli	A-B toxin	Genotoxin (colibactin); binds to adenines in DNA.
Skin and soft tissue infection	MRSA	Membrane-disrupting	Leukocidins; kill phagocytic leukocytes.
Gas gangrene and food poisoning	C. perfringens and other species	Membrane-disrupting	Hemolysins; lyse erythrocytes.
Antibiotic-associated diarrhea	Clostridioides difficile	Membrane-disrupting	Exotoxins; cause secretion of fluids and electrolytes that result in diarrhea.
Food poisoning	S. aureus	Superantigen	Superantigens; cause secretion of fluids and electrolytes that result in diarrhea, nausea, and vomiting.
Toxic shock syndrome (TSS)	S. aureus	Superantigen	Superantigens; cause fever, shock, and death.

Endotoxins

Characteristics and Effects

Lipid A portion of lipopolysaccharides (LPS) of gram-negative bacteria.
Released during bacterial multiplication and when gram-negative bacteria die.
Stimulate macrophages to release large quantities of cytokines.
Cause fever, chills, weakness, generalized aches, disseminated intravascular coagulation, endotoxic shock (life-threatening drop in blood volume and pressure), and may weaken the blood-brain barrier.

Detection

Limulus amebocyte lysate (LAL) assay: Used to test for endotoxins. Blood of horseshoe crabs contains amebocytes that lyse in the presence of endotoxin, producing a clot.

Plasmids, Lysogeny, and Pathogenicity

Genetic Elements Affecting Virulence

Plasmids: May carry genes for toxins, antibiotic resistance, and enzymes.
R plasmids: Encode resistance to antibiotics.
Virulence plasmids: Encode factors affecting pathogenicity (e.g., tetanus neurotoxin, staphylococcal enterotoxin).
Lysogenic conversion: Incorporation of a prophage can change microbial characteristics (e.g., diphtheria toxin genes).

Pathogenic Properties of Viruses

Mechanisms of Evasion and Damage

Intracellular location prevents immune detection.
Attachment via host cell surface molecules.
Direct attack on immune system components.
Methylation of viral RNA to mimic host RNA.
Antigenic variation.

Cytopathic Effects (CPE)

Visible effects of viral infection on host cells.
Cytocidal effects: Kill host cells.
Noncytocidal effects: Cause cell damage but not death.
Disruption of cell junctions, induction of cytokine storm, inhibition of macromolecular synthesis, lysosomal enzyme release, inclusion body formation, syncytium formation, antigenic changes, chromosomal damage, transformation (loss of contact inhibition, cancer), and interferon production.

Interferons

Alpha and beta interferons produced by virally infected cells protect neighboring cells by inhibiting viral protein synthesis and inducing apoptosis.
Some viruses evade interferons by blocking their synthesis.

Pathogenic Properties of Fungi, Protozoa, Helminths, and Algae

Fungi

Toxic metabolic products provoke allergic responses.
Trichothecene toxins inhibit protein synthesis.
Proteases modify host cell membranes (e.g., Candida albicans).
Capsules prevent phagocytosis (e.g., Cryptococcus neoformans).
Ergot alkaloids cause hallucinations; aflatoxin (from Aspergillus) is carcinogenic; mycotoxins from mushrooms are neurotoxic.

Protozoa

Cause symptoms via presence and waste products.
Evade defenses by digesting cells/tissue fluids (Giardia intestinalis), growing in phagocytes (Toxoplasma gondii), and antigenic variation (Trypanosoma).

Helminths

Use host tissue for growth, produce large masses, cause cellular damage, and produce waste products that cause symptoms.

Algae

Some produce neurotoxins (e.g., saxitoxin) causing paralytic shellfish poisoning, often associated with red tides (blooms of Alexandrium).

Portals of Exit

How Pathogens Leave the Host

Respiratory tract: Coughing and sneezing.
Gastrointestinal tract: Feces and saliva.
Genitourinary tract: Urine; secretions from penis and vagina.
Skin
Blood: Arthropod bites; needles or syringes.

Summary Table: Exotoxins vs. Endotoxins

Feature	Exotoxins	Endotoxins
Chemical Nature	Protein	Lipid A (LPS)
Source	Gram-positive and Gram-negative bacteria	Gram-negative bacteria
Effect	Specific; highly toxic	General; less potent
Immunity	Antitoxins available	No antitoxins
Heat Stability	Unstable	Stable
Fever Production	Usually none	Yes

Additional info: These notes synthesize textbook slides and lecture content for Chapter 15, providing a comprehensive overview of microbial mechanisms of pathogenicity, including tables and expanded academic context for exam preparation.