Microbial Mechanisms of Pathogenicity – Chapter 15 Study Notes

Microbial Mechanisms of Pathogenicity

Introduction

Pathogenicity refers to the ability of microorganisms to cause disease, while virulence describes the degree of pathogenicity. Understanding how microbes invade hosts, evade defenses, and cause damage is essential for microbiology students studying infectious diseases.

How Microorganisms Enter a Host

Portals of Entry

Microorganisms must enter the host through specific portals to initiate infection. Most pathogens have a preferred portal of entry that is optimal for their survival and proliferation.

• Mucous membranes: Includes the respiratory tract, digestive canal, genital system, urinary system, and conjunctiva.

• Skin: Generally impenetrable unless compromised; entry possible via hair follicles and sweat gland ducts.

• Parenteral route: Direct deposition into tissues beneath the skin or mucous membranes via punctures, injections, bites, cuts, wounds, or surgery.

Example: The respiratory tract is the most commonly used portal of entry for airborne pathogens.

Numbers of Invading Microbes

ID50 and LD50

The severity of infection and toxicity is often quantified using ID50 and LD50 values.

• ID50: Infectious dose for 50% of a sample population; measures virulence.

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

Equations:

• $ID_{50}$: Number of organisms required to infect 50% of hosts

• $LD_{50}$: Amount of toxin required to kill 50% of hosts

Bacillus anthracis ID50 by Portal of Entry

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

Toxin LD50 Values

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

Adherence

Mechanisms of Attachment

Pathogens must adhere to host tissues to establish infection. This process involves specific interactions between microbial adhesins (ligands) and host cell receptors.

• Glycocalyx: Example: Streptococcus mutans uses dextran to adhere to teeth.

• Fimbriae: Example: Actinomyces fimbriae adhere to the glycocalyx of S. mutans.

• Viral spikes: Example: SARS-CoV-2 spikes bind to ACE2 receptors on host cells.

Capsules and Cell Wall Components

Capsules

Capsules are glycocalyx layers surrounding the cell wall that impair phagocytosis, allowing pathogens to evade immune responses.

• Streptococcus pneumoniae – pneumonia

• Haemophilus influenzae – pneumonia and meningitis

• Bacillus anthracis – anthrax

• Yersinia pestis – plague

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 Produced by Pathogens

Pathogenic bacteria secrete enzymes that facilitate invasion and evasion of host defenses.

• Coagulases: Coagulate fibrinogen to form fibrin.

• Kinases: Digest fibrin clots.

• Hyaluronidase: Digests hyaluronic acid, which holds cells together.

• Collagenase: Breaks down collagen.

• IgA proteases: Destroy IgA antibodies.

Antigenic Variation

Some pathogens evade immune responses by altering their surface antigens, rendering host antibodies ineffective.

• Influenza virus

• Neisseria gonorrhoeae

• Trypanosoma brucei gambiense

Penetration into the Host

Invasins and Survival Strategies

Bacteria use invasins to rearrange host cell actin, causing membrane ruffling and engulfment. Some bacteria use actin to move between cells or survive inside phagocytes by various mechanisms.

• Invasins: Surface proteins that rearrange actin filaments (e.g., Shigella, Listeria).

• Survival inside phagocytes:

  • Requirement for low pH in phagolysosome

  • Escape from phagosome before lysosomal fusion

  • Prevention of fusion of lysosome with phagosome

Biofilms

Biofilms are communities of microorganisms encased in a protective matrix. They resist antibiotics and disinfectants and play a significant role in evading phagocytes.

• Involved in 65% of all infections

• Biofilm bacteria are shielded by extracellular polymeric substance (EPS)

Using the Host's Nutrients: Siderophores

Iron is essential for most pathogenic bacteria. Siderophores are proteins secreted by pathogens that bind iron more tightly than host iron-binding proteins, facilitating iron acquisition.

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

Direct Damage to Host Cells

Pathogens can cause direct damage by disrupting host cell function, using host nutrients, producing waste products, and multiplying within host cells, leading to cell rupture.

Production of Toxins

Toxins are poisonous substances produced by microorganisms that can 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

Properties and Types

Exotoxins are proteins produced and secreted by bacteria, highly specific for their targets, and often highly lethal. They are soluble in bodily fluids and can be neutralized by antitoxins or inactivated as toxoids for vaccines.

• 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 leading to cancer.

• Membrane-disrupting toxins: Lyse host cells by disrupting plasma membranes (e.g., leukocidins, hemolysins, streptolysins).

• Superantigens: Cause intense immune responses by stimulating cytokine release from T cells, leading to fever, nausea, vomiting, diarrhea, shock, and death.

Table: Diseases Caused by Exotoxins

Disease	Bacterium	Type of Exotoxin	Mechanism
Botulism	Clostridium botulinum	A-B	Neurotoxin; prevents transmission of nerve impulses
Tetanus	C. tetani	A-B	Neurotoxin; blocks relaxation pathway in muscles
Diphtheria	Corynebacterium diphtheriae	A-B	Cytotoxin; inhibits protein synthesis
Cholera	V. cholerae	A-B	Enterotoxin; causes secretion of large amounts of fluids
Anthrax	Bacillus anthracis	A-B	Cytotoxin; disrupts cell signaling
Food poisoning	S. aureus	Superantigen	Enterotoxin; causes secretion of fluids and electrolytes

Endotoxins

Properties and Effects

Endotoxins are the lipid A portion of lipopolysaccharides (LPS) found in the outer membrane of gram-negative bacteria. They are released during bacterial multiplication and cell death, causing fever, chills, weakness, and shock.

• Stimulate macrophages to release large quantities of cytokines

• Cause disseminated intravascular coagulation

• May weaken the blood-brain barrier

Detection

The Limulus amebocyte lysate (LAL) assay uses horseshoe crab blood to detect endotoxins, as amebocytes lyse and form a clot in the presence of endotoxin.

Table: Exotoxins vs. Endotoxins

Property	Exotoxins	Endotoxins
Bacterial Source	Gram-positive and gram-negative bacteria	Gram-negative bacteria
Chemistry	Proteins, usually with two parts (A-B)	Lipid portion (lipid A) of LPS
Pharmacology	Specific for particular cell structure/function	General effects (fever, weakness, aches, shock)
Heat Stability	Unstable; destroyed at 60–80°C	Stable; withstands autoclaving (121°C for 1 hour)
Toxicity	High	Low
Fever-Producing	No	Yes
Immunology	Can be converted to toxoids for vaccines	Not easily neutralized by antitoxin
Lethal Dose	Small	Considerable
Representative Diseases	Gas gangrene, tetanus, botulism, diphtheria, scarlet fever	Typhoid fever, urinary tract infections, meningococcal meningitis

Plasmids, Lysogeny, and Pathogenicity

Plasmids are extrachromosomal DNA elements that may carry genes for toxins, antibiotic resistance, and enzymes. Lysogenic conversion occurs when a bacterium incorporates a prophage, altering its characteristics and pathogenicity.

• R plasmids: Encode resistance to antibiotics

• Virulence plasmids: Encode toxins and virulence factors (e.g., tetanus neurotoxin, staphylococcal enterotoxin)

• Lysogenic conversion: Can result in production of toxins (e.g., diphtheria toxin)

Pathogenic Properties of Viruses

Evading Host Defenses

• 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)

• Cytocidal effects: Kill host cells

• Noncytocidal effects: Cause cell damage without death; infected cells may continue to grow and divide

• CPE can be used to diagnose viral infections and vary by virus

*Additional info: These notes are expanded and structured for clarity and completeness, including definitions, examples, and tables for comparison. Equations are provided in LaTeX format as required.*