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Microbial Mechanisms of Pathogenicity
Chapter 15 Microbial Mechanisms of Pathogenicity
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Mechanisms of Pathogenicity
Pathogenicity: the ability to cause disease Virulence: the extent of pathogenicity
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Portals of Entry Mucous membranes Skin Parenteral route
Preferred portal of entry
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Numbers of Invading Microbes
ID50: infectious dose for 50% of the test population LD50: lethal dose (of a toxin) for 50% of the test population
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Bacillus anthracis Portal of Entry ID50 Skin 10–50 endospores
Inhalation 10,000–20,000 endospores Ingestion 250,000–1,000,000 endospores
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Toxins Portal of Entry ID50 Botulinum 0.03 ng/kg Shiga toxin 250 ng/kg
Staphylococcal enterotoxin 1350 ng/kg
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Adherence Adhesins/ligands bind to receptors on host cells
Glycocalyx: Streptococcus mutans Fimbriae: Escherichia coli M protein: Streptococcus pyogenes Form biofilms
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Adhesin (ligand) Pathogen Host cell surface Receptor
Figure 15.1a Adherence. Adhesin (ligand) Pathogen Host cell surface Receptor Surface molecules on a pathogen, called adhesins or ligands, bind specifically to complementary surface receptors on cells of certain host tissues.
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Figure 15.1b-c Adherence. E. coli bacteria (yellow-green) on human urinary bladder cells Bacteria (purple) adhering to human skin
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Capsules Prevent phagocytosis Streptococcus pneumoniae
Haemophilus influenzae Bacillus anthracis
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Cell Wall Components M protein resists phagocytosis
Streptococcus pyogenes Opa protein inhibits T helper cells Neisseria gonorrhoeae Mycolic acid (waxy lipid) resists digestion Mycobacterium tuberculosis
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Enzymes Coagulase: coagulates fibrinogen Kinases: digest fibrin clots
Hyaluronidase: hydrolyzes hyaluronic acid Collagenase: hydrolyzes collagen IgA proteases: destroy IgA antibodies
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Blocked coronary artery
Chapter 15, unnumbered figure A, p. 434. Blocked coronary artery
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Necrotizing fasciitis
Chapter 15, unnumbered figure B, p. 434. Necrotizing fasciitis
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Mechanism of streptokinase
Chapter 15, unnumbered figure C, p. 434. Mechanism of streptokinase Streptokinase Blood clot Plasminogen Plasmin Fibrin breakdown
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Ruffling of host cell plasma membrane Salmonella typhimurium
Figure 15.2 Salmonella entering intestinal epithelial cells as a result of ruffling. Ruffling of host cell plasma membrane Salmonella typhimurium
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Clone A Clone B Clone C 1 2 3 4 Weeks after infection
Figure How trypanosomes evade the immune system. Clone A Clone B Clone C Relative number of trypanosomes 1 2 3 4 Weeks after infection
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Penetration into the Host Cell Cytoskeleton
Invasins Salmonella alters host actin to enter a host cell Use actin to move from one cell to the next Listeria
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Figure 21.12 Cold sores, or fever blisters, caused by herpes simplex virus.
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Figure 15.3 Structure of enterobactin, one type of bacterial siderophore.
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Direct Damage Disrupt host cell function Produce waste products Toxins
ANIMATION Virulence Factors: Penetrating Host Tissues ANIMATION Virulence Factors: Enteric Pathogens
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The Production of Toxins
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
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Figure 15.4 Mechanisms of Exotoxins and Endotoxins.
Exotoxins are proteins produced inside pathogenic bacteria, most commonly gram-positive bacteria, as part of their growth and metabolism. The exotoxins are then secreted into the surrounding medium during log phase. Endotoxins are the lipid portions of lipopolysaccharides (LPS) that are part of the outer membrane of the cell wall of gram-negative bacteria (lipid A; see Figure 4.13c). The endotoxins are liberated when the bacteria die and the cell wall breaks apart. Cell wall Exotoxin: toxic substances released outside the cell Salmonella typhimurium, an example of a gram-negative bacterium that produces endotoxins Clostridium botulinum, an example of a gram-positive bacterium that produces exotoxins Endotoxins: toxins composed of lipids that are part of the cell membrane
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Exotoxins Specific for a structure or function in host cell
ANIMATION Virulence Factors: Exotoxins
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Figure 15.5 The action of an A-B exotoxin.
DNA Exotoxin mRNA 1 Bacterium produces and releases exotoxin. A (active) A Exotoxin polypeptides B (binding) B Bacterium A B Receptor Plasma membrane 2 B (binding) component of exotoxin attaches to host cell receptor. Nucleus Cytoplasm Host cell 3 A-B exotoxin enters host cell by receptor-mediated endocytosis. A B 4 A-B exotoxin enclosed in pinched-off portion of plasma membrane during pinocytosis. A B B 5 A-B components of exotoxin separate. The A component alters cell function by inhibiting protein synthesis. The B component is released from the host cell. A B B A Protein
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Membrane-Disrupting Toxins
Lyse host’s cells by Making protein channels in the plasma membrane Leukocidins Hemolysins Streptolysins Disrupting phospholipid bilayer
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Superantigens Cause an intense immune response due to release of cytokines from host cells Symptoms: fever, nausea, vomiting, diarrhea, shock, and death
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By-products of growing cell
Exotoxin Source Mostly gram-positive Relation to microbe By-products of growing cell Chemistry Protein Fever? No Neutralized by antitoxin? Yes LD50 Small
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Exotoxins and Lysogenic Conversion
Lysogeny Corynebacterium diphtheriae A-B toxin + Streptococcus pyogenes Membrane-disrupting erythrogenic toxin Clostridium botulinum A-B toxin; neurotoxin C. tetani Vibrio cholerae A-B toxin; enterotoxin Staphylococcus aureus Superantigen
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Endotoxins Source Gram-negative Relation to Microbe Outer membrane
Chemistry Lipid A Fever? Yes Neutralized by Antitoxin? No LD50 Relatively large
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Figure 15.6 Endotoxins and the pyrogenic response.
Macrophage Endotoxin Hypothalamus of brain Nucleus Cytokines Prostaglandin Fever Blood vessel Pituitary gland Vacuole Bacterium 1 A macrophage ingests a gram-negative bacterium. 2 The bacterium is degraded in a vacuole, releasing endotoxins that induce the macrophage to produce cytokines IL-1 and TNF-. 3 The cytokines are released into the bloodstream by the macrophages, through which they travel to the hypothalamus of the brain. 4 The cytokines induce the hypothalamus to produce prostaglandins, which reset the body’s “thermostat” to a higher temperature, producing fever.
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LAL Assay Limulus amebocyte lysate assay
Amebocyte lysis produces a clot Endotoxin causes lysis ANIMATION Virulence Factors: Endotoxins
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Inclusion body Cytoplasmic mass Nuclei
Figure 15.7 Some cytopathic effects of viruses. Inclusion body Cytoplasmic mass Nuclei
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Figure 15.8 Transformed cells in culture.
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Pathogenic Properties of Fungi
Fungal waste products may cause symptoms Chronic infections provoke an allergic response Trichothecene toxins inhibit protein synthesis Fusarium Proteases Candida, Trichophyton Capsule prevents phagocytosis Cryptococcus
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Pathogenic Properties of Fungi
Ergot toxin Claviceps Aflatoxin Aspergillus Mycotoxins Neurotoxins: phalloidin, amanitin Amanita
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Pathogenic Properties of Protozoa
Presence of protozoa Protozoan waste products may cause symptoms Avoid host defenses by Growing in phagocytes Antigenic variation
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Pathogenic Properties of Helminths
Use host tissue Presence of parasite interferes with host function Parasite’s metabolic waste can cause symptoms
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Pathogenic Properties of Algae
Paralytic shellfish poisoning Dinoflagellates Saxitoxin
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Figure A red tide.
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Portals of Exit Respiratory tract Gastrointestinal tract
Coughing and sneezing Gastrointestinal tract Feces and saliva Genitourinary tract Urine and vaginal secretions Skin Blood Arthropods that bite; needles or syringes
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Figure 15.9 Microbial Mechanisms of Pathogenicity.
When the balance between host and microbe is tipped in favor of the microbe, an infection or disease results. Learning these mechanisms of microbial pathogenicity is fundamental to understanding how pathogens are able to overcome the host’s defenses. H1N1 flu virus penetration or evasion of host defenses damage to host cells Number of invading microbes portals of entry portals of exit Mucous membranes Capsules Cell wall components Enzymes Antigenic variation Invasins Intracellular growth Siderophores Direct damage Toxins Generally the same as the portals of entry for a given microbe: • Respiratory tract • Gastrointestinal tract • Genitourinary tract • Conjunctiva • Exotoxins • Endotoxins • Mucous membranes • Skin • Parenteral route Skin Parenteral route Lysogenic conversion Cytopathic effects Adherence Mycobacterium intracellulare Clostridium tetani Micrographs are not shown to scale.
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