Chapter 15_Microbial Mechanisms of Pathogenicity: Study Notes

Microbial Mechanisms of Pathogenicity

Definitions and Key Concepts

Understanding how microbes cause disease is fundamental in microbiology. Pathogenicity is the ability of a microorganism to cause disease by overcoming host defenses, while virulence refers to the degree or extent of pathogenicity. Microbial toxins, such as exotoxins and endotoxins, play a crucial role in disease development.

• Toxin: Substance that contributes to pathogenicity.

• Toxigenicity: Ability to produce a toxin.

• Toxemia: Presence of toxin in the host’s blood.

• Toxoid: Inactivated toxin used in a vaccine.

• Antitoxin: Antibodies against a specific toxin.

Mechanisms of Pathogenesis

For a microbe to cause disease, it must satisfy four conditions and have an exit strategy:

1. Gain entry into the host

2. Adhere and colonize (avoid dislodging/multiply in tissue)

3. Resist the defenses of the host

4. Invade and spread

5. Exit from host and survive (to regain entry)

Portals of Entry

Main Portals of Entry

Microbes enter the host through specific portals:

• Mucous membranes: Respiratory, gastrointestinal, genitourinary tracts, conjunctiva

• Skin: Through abrasions, wounds, hair follicles, sweat ducts

• Parenteral route: Non-oral entry (e.g., intramuscular, subcutaneous, intravenous)

Adherence to Host Cells

Microbes use surface molecules called adhesins or ligands to bind specifically to complementary surface receptors on host cells. This interaction is highly specific and is essential for colonization.

• Glycocalyx: Streptococcus mutans

• Fimbriae: Escherichia coli

• M protein: Streptococcus pyogenes

Biofilm formation further enhances adherence and colonization.

Virulence Factors

Cell Wall Components and Capsules

Microbial surface structures contribute to pathogenicity by resisting host defenses:

• Capsules: Prevent phagocytosis (Klebsiella pneumoniae, Streptococcus pneumoniae)

• M protein: Resists phagocytosis (Streptococcus pyogenes)

• Opa protein: Inhibits T helper cells (Neisseria gonorrhoeae)

• Mycolic acid: Resists digestion (Mycobacterium tuberculosis)

Antigenic Variation

Microbes can alter their surface antigens to evade the immune system. This process, known as antigenic variation, is seen in viruses (e.g., influenza) and bacteria (e.g., Borrelia recurrentis).

Enzymes as Virulence Factors

Bacterial enzymes facilitate invasion and spread by degrading host tissues:

• Coagulases: Clot fibrinogen in plasma, protecting bacteria from phagocytosis

• Kinases: Digest fibrin clots, allowing spread

• Hyaluronidase: Degrades hyaluronic acid, aiding tissue penetration

• Collagenase: Digests collagen, facilitating spread through connective tissue

• IgA proteases: Destroy IgA antibodies

Penetration into Host Cell Cytoskeleton

Some bacteria use invasins to rearrange actin filaments of the host cell cytoskeleton, facilitating entry and movement within and between cells (e.g., Salmonella, Listeria).

Using Host Nutrients: Siderophores

Bacteria secrete siderophores to scavenge iron from host iron-binding proteins, which is essential for their growth and survival.

Host Damage and Toxins

Direct Damage

Bacteria can cause direct damage by multiplying inside host cells, disrupting cell function, and producing waste products.

Bacterial Toxins

Bacterial toxins are classified as exotoxins and endotoxins:

• Exotoxins: Secreted proteins, highly toxic, heat labile, produced mainly by Gram-positive bacteria

• Endotoxins: Lipid A component of LPS in Gram-negative bacteria, released upon cell death, heat stable

Exotoxin Types and Mechanisms

• A-B toxins: Consist of an active (A) and binding (B) component; the A component alters cell function, often by inhibiting protein synthesis

• Membrane-disrupting toxins: Cause cell lysis by disrupting plasma membranes

• Superantigens: Trigger excessive immune response by binding to MHC II and T cells, causing massive cytokine release

Exotoxin Classification

• Diphtheria toxin: A-B toxin

• Botulinum toxin: A-B neurotoxin

• Tetanus toxin: A-B neurotoxin

• Vibrio enterotoxin: A-B enterotoxin

• Staphylococcal enterotoxin: Superantigen

Lysogeny and Pathogenicity

Some bacteria acquire toxin genes via lysogenic conversion, where a bacteriophage integrates its DNA into the bacterial genome, conferring new virulence properties.

Endotoxins and the Pyrogenic Response

Mechanism of Endotoxin Action

Endotoxins stimulate macrophages to release cytokines (IL-1, TNF-α), which travel to the hypothalamus and induce fever by triggering prostaglandin production.

Comparison of Exotoxins and Endotoxins

Property	Exotoxin	Endotoxin
Source	Mostly Gram-positive	Gram-negative
Relation to Microbe	By-products of growing cell	Outer membrane
Chemistry	Protein	Lipid A
Fever?	No	Yes
Neutralized by Antitoxin?	Yes	No
LD50	Small	Relatively large

Pathogenic Properties of Other Infectious Agents

Fungi

• Fungal waste products may cause symptoms

• Chronic infections provoke allergic responses

• Trichothecene toxins inhibit protein synthesis (Fusarium)

• Proteases (Candida, Trichophyton)

• Capsule prevents phagocytosis (Cryptococcus)

• Ergot toxin (Claviceps purpurea), aflatoxin (Aspergillus), neurotoxins (phalloidin, amanitin)

Protozoa

• Waste products cause symptoms

• Evade host defenses by growing in phagocytes (Toxoplasma) and antigenic variation (Giardia, Trypanosoma)

Helminths

• Use host tissue and interfere with host function

• Metabolic waste causes symptoms (e.g., elephantiasis by Wuchereria bancrofti)

Algae

• Produce neurotoxins (e.g., saxitoxin from dinoflagellates causing paralytic shellfish poisoning)

Portals of Exit

Portal of Exit

Microbes exit the host through the same portals as entry: mucous membranes, skin, parenteral route. This is essential for transmission and survival.

Summary Diagram: Microbial Pathogenicity

The balance between host and microbe determines infection outcome. Mechanisms include portals of entry, penetration/evasion of host defenses, damage to host cells, and portals of exit.

Nosocomial Infections: MRSA

MRSA (Methicillin Resistant Staphylococcus aureus)

• Causes life-threatening necrotizing illness due to leucocidin toxin

• Resistance to methicillin and vancomycin

• USA100 MRSA: 92% infections in healthcare

• USA300 MRSA: 89% infections in community

• Acquisition of vanA gene from Enterococcus species