Microbial Pathogenicity and Virulence

• Pathogenicity is the ability to cause disease, while virulence is the degree of pathogenicity.

Microorganism Entry

• Mucous membranes, skin, and the parenteral route are the main portals.
• The respiratory tract is the most frequently traveled portal for infectious microorganisms.
• Depositing directly into tissues when barriers are penetrated classifies as the parenteral route.
• Most pathogens have preferred entry points.

Numbers of Invading Microbes

• ID50, or infectious dose is the dose required to infect 50% of a sample population, which measures a microbe's virulence.
• LD50, or lethal dose is the dose required to kill 50% of a sample population, which measures potency of a toxin.
• Bacillus anthracis' ID50 varies amongst entry portal, 10-50 endospores through the skin, 10,000-20,000 endospores through inhalation, and 250,000-1,000,000 endospores through ingestion.
• The LD50 of botulinum toxin is 0.03ng/kg, 250ng/kg for shiga toxin, and 1350 ng/kg for staphylococcal enterotoxin.

Adherence

• Almost all pathogens adhere to host tissues via adhesion.
• Adhesins/ligands on pathogens bind to receptors on host cells that are often located on the glycocalyx, fimbriae, pili, and flagella.
• Glycoproteins and lipoproteins are the majority of adhesins.
• Host cell receptors usually consist of sugars.
• Microbes form biofilms, which are communities share nutrients and protect microbes from disinfectants and antibiotics.

Capsules and Cell Wall Components

• Capsules are glycocalyx around the cell wall that impair phagocytosis, which includes Streptococcus pneumoniae (pneumonia), Haemophilus influenzae (pneumonia and meningitis), Bacillus anthracis (anthrax) and Yersinia pestis (plague).
• 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.
• Kinases digest fibrin clots.
• Hyaluronidase digests polysaccharides that hold cells together.
• Collagenase breaks down collagen.
• IgA proteases destroy IgA antibodies.

Antigenic Variation

• Pathogens alter surface antigens, making antibodies ineffective.

Penetration into Host Cell Cytoskeleton

• Invasins of Salmonella and E. coli are surface proteins produced by bacteria that rearrange actin filaments of the cytoskeleton to cause membrane ruffling.
• Some bacteria use actin to move from one cell, such as Shigella and Listeria, which utilize glycoprotein cadherin to bridge junctions between cells.

Siderophores

• Iron is required for most pathogenic bacteria.
• Siderophores are proteins secreted by pathogens that bind iron more tightly than host cells.

Direct Damage

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

Toxins

• Toxins are poisonous substances produced by microorganisms that can cause fever, cardiovascular problems, diarrhea, and shock.
• Toxigenicity is the ability of a microorganism to produce a toxin.
• Toxemia refers to the presence of toxin in the host's blood.
• Intoxications refer to the presence of toxin without microbial growth.

Exotoxins

• Exotoxins consist of proteins produced and secreted by bacteria that are soluble in bodily fluids and destroy host cells/inhibit metabolic functions.
• Antitoxins are antibodies against specific exotoxins.
• Toxoids are inactivated exotoxins used in vaccines.
• A-B toxins contain an enzyme component (A part) and a binding component (B part), an example being diphtheria toxin.
• Membrane-disrupting toxins lyse host cells by disrupting plasma membranes, which include Leukocidins that kill phagocytic leukocytes, hemolysins that kill erythrocytes by forming protein channels, and streptolysins that consist of hemolysins produced by streptococci.
• Superantigens cause an intense immune response by releasing cytokines from host cells (T cells), which causes symptoms of fever, nausea, vomiting, diarrhea, shock, and death.
• Genotoxins damage DNA, causing mutations, disrupting cell division, which leads to cancer.

Endotoxins

• Lipid A is a portion of lipopolysaccharides (LPS) of gram-negative bacteria.
• These are released during bacterial multiplication or when gram-negative bacteria die.
• Endotoxins stimulate macrophages to release cytokines, producing chills, fevers, aches; in some cases, shock.
• The limulus amebocyte lysate (LAL) assay tests for endotoxins, which consists of blood from horseshoe crabs containing amebocytes that will lyse in the presence of endotoxin, producing a clot.

Plasmids & Lysogeny

• Plasmids may carry genes for toxins, production of antibiotics, and enzymes, such as tetanus neurotoxin and heat labile enterotoxin.
• Lysogenic conversion changes characteristics of a microbe due to prophage incorporation, forming diptheria or erythrogenic toxins.

Cytopathic Effects of Viruses

• Stopping cell synthesis.
• Causing cell lysosomes to release enzymes.
• Creating inclusion bodies in the cell 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 in the cell, leading to cancer.
• Producing interferons to protect uninfected cells.

Pathogenic Properties of Fungi

• Includes toxic metabolic products.
• Provokes an allergic response.
• Includes trichothecene toxins which inhibit protein synthesis.
• Alters host cell membranes via proteases.
• Prevents phagocytosis through capsules.
• Ergot alkaloid toxins can cause hallucinations.
• Aflatoxin is a carcinogenic toxin produced by Aspergillus.
• Mycotoxins produced by mushrooms are neurotoxic, such as phalloidin and amanitin.

Protozoa

• Presence of protozoa and their waste products causes symptoms.
• They avoid host defenses by digesting cells/tissue fluids, growing in phagocytes, or antigenic variation.

Helminths

• Utilize host tissue for growth.
• Produce large masses to cause cellular damage.
• Release waste products that cause symptoms.

Algae

• Some (e.g. Alexandrium) produce a neurotoxin called saxitoxin, which results in paralytic shellfish poisoning.

Portals of Exit

• Respiratory tract.
• Gastrointestinal tract.
• Genitourinary tract.
• Skin.
• Blood.