Microbial Mechanisms of Pathogenicity: Study Notes

Microbial Mechanisms of Pathogenicity

Portals of Entry

Pathogens must enter the host through specific sites known as portals of entry. Most pathogens have a preferred portal, which influences their ability to cause disease.

• Mucous membranes: Includes the respiratory tract, gastrointestinal tract (enteral route), genitourinary tract, placenta, and conjunctiva of the eye.

• Parenteral route: Entry through broken skin, wounds, bites, injections, or punctures.

Numbers of Invading Microbes: ID50 and LD50

The likelihood of disease depends on the number of microbes entering the host. Two important measures are:

• ID50 (Infectious Dose 50): The number of pathogens required to infect 50% of a sample population.

• LD50 (Lethal Dose 50): The dose of a toxin that kills 50% of a sample population, often measured in mg/kg body weight.

Adherence

Almost all pathogens must attach to host tissues in a process called adherence (or adhesion). This is mediated by specific molecules:

• Adhesins (ligands): Surface molecules on the pathogen that bind to receptors on host cells.

• Structures involved: Glycocalyx, fimbriae.

• Biofilms: Microbes may form biofilms, which are communities that share nutrients and enhance adherence.

How Pathogens Penetrate Host Defenses

Capsules

Some bacteria produce a glycocalyx capsule around their cell wall, which impairs phagocytosis and increases pathogenicity.

• Examples: 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 (Mycobacterium tuberculosis).

Enzymes

• Coagulases: Coagulate fibrinogen, protecting bacteria from phagocytosis.

• Kinases: Digest fibrin clots, allowing bacteria to spread.

• Hyaluronidase: Digests polysaccharides that hold cells together.

• Collagenase: Breaks down collagen in connective tissue.

• IgA proteases: Destroy IgA antibodies, reducing immune defense.

Penetration into the Host Cell Cytoskeleton

Bacteria use invasins (surface proteins) to rearrange actin filaments of the host cell cytoskeleton, causing membrane ruffling and facilitating entry.

• Examples: Shigella, Listeria, Salmonella.

How Bacterial Pathogens Damage Host Cells

Using the Host's Nutrients: Siderophores

Pathogenic bacteria require iron, which is tightly bound by host proteins. Siderophores are proteins secreted by pathogens that bind iron more tightly than host molecules, facilitating iron acquisition.

• Host iron-binding molecules: Transferrin, ferritin, lactoferrin, hemoglobin.

Direct Damage

• Disrupts host cell function.

• Uses host cell nutrients.

• Produces waste products.

• Multiplies in host cells, causing cell rupture.

Production of Toxins

Toxins are poisonous substances produced by microorganisms. They 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

Exotoxins are proteins produced and secreted by bacteria, usually gram-positive, and are soluble in bodily fluids. They destroy host cells and inhibit metabolic functions.

• Antitoxins: Antibodies against specific exotoxins.

• Toxoids: Inactivated exotoxins used in vaccines.

A-B Toxins

A-B toxins consist of an enzyme component (A part) and a binding component (B part). The B part binds to the host cell, and the A part exerts toxic effects.

• Example: Diphtheria toxin.

Membrane-Disrupting Toxins

• Leukocidins: Kill phagocytic leukocytes.

• Hemolysins: Kill erythrocytes by forming protein channels.

• Streptolysins: Hemolysins produced by streptococci.

Superantigens

Superantigens cause an intense immune response due to cytokine release from host cells, leading to fever, nausea, vomiting, diarrhea, shock, and death.

Genotoxins

Genotoxins damage DNA, causing mutations, disrupting cell division, and potentially leading to cancer.

Endotoxins

Endotoxins are the lipid A portion of lipopolysaccharides (LPS) found in the cell wall of gram-negative bacteria. They are released during bacterial multiplication and when bacteria die.

• Stimulate macrophages to release cytokines.

• Can cause disseminated intravascular coagulation.

Comparison of Exotoxins and Endotoxins

The following table summarizes the differences between exotoxins and endotoxins:

Property	Exotoxins	Endotoxins
Bacterial Source	Mostly from gram-positive bacteria	Gram-negative bacteria
Chemistry	Proteins, usually with two parts (A-B)	Lipid portion of LPS
Pharmacology Effect	Specific for a particular cell structure or function	General, such as fever, weakness, aches
Heat Stability	Unstable	Stable
Toxicity	High	Low
Fever Producing	No	Yes
Immunity	Can be converted to toxoids for immunization	Not easily neutralized by antibodies
Lethal Dose	Small	Large
Representative Diseases	Tetanus, botulism, diphtheria	Typhoid fever, urinary tract infections

Plasmids, Lysogeny, and Pathogenicity

• Plasmids: May carry genes for toxins, antibiotic production, and enzymes.

• Lysogenic conversion: Changes characteristics of a microbe due to incorporation of a prophage.

Pathogenic Properties of Viruses

Cytopathic Effects (CPE)

Cytopathic effects are visible changes in host cells due to viral infection. These effects include:

• Stopping cell synthesis

• Causing cell lysosomes to release enzymes

• Creating inclusion bodies in the cytoplasm

• Fusing cells to create a syncytium

• Changing host cell function or inducing chromosomal changes

• Inducing antigenic changes on the cell surface

• Loss of contact inhibition, leading to cancer

• Producing interferons to protect uninfected cells

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.

• Capsules prevent phagocytosis.

• Ergot alkaloid toxins cause hallucinations.

• Aflatoxin is a carcinogenic toxin produced by Aspergillus.

• Mycotoxins (e.g., phalloidin, amanitin) are neurotoxic.

Protozoa

• Presence and waste products cause symptoms.

• Evade host defenses by digesting cells and tissue fluids, growing in phagocytes, and antigenic variation.

Helminths

• Use host tissue for growth.

• Produce large masses and waste products that cause symptoms.

Algae

• Some produce neurotoxins, such as saxitoxin, causing paralytic shellfish poisoning.

Portals of Exit

Pathogens leave the host through specific portals of exit, which are generally the same as the portals of entry.

• Respiratory tract: Coughing and sneezing

• Gastrointestinal tract: Feces and saliva

• Genitourinary tract: Urine; secretions from the penis and vagina

• Skin

• Blood: Arthropods that bite; needles or syringes

Key Concepts

• Portals of entry and exit are critical for infection.

• Pathogens adhere, penetrate or evade host defenses, and damage host tissues.

• Multiple factors contribute to pathogenicity, including toxins, enzymes, and genetic elements.