Upload
ferdinand-scott
View
217
Download
1
Embed Size (px)
Citation preview
© 2013 Pearson Education, Inc. Lectures prepared by Christine L. Case
Chapter 15
Microbial Mechanisms of Pathogenicity
© 2013 Pearson Education, Inc.
© 2013 Pearson Education, Inc.
Mechanisms of Pathogenicity
Pathogenicity: the ability to cause disease Virulence: the extent of pathogenicity
© 2013 Pearson Education, Inc.
Portals of Entry
Mucous membranes Skin Parenteral route Preferred portal of entry
© 2013 Pearson Education, Inc.
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
© 2013 Pearson Education, Inc.
Portal of Entry ID50
Skin 10–50 endospores
Inhalation 10,000–20,000 endospores
Ingestion 250,000–1,000,000 endospores
Bacillus anthracis
© 2013 Pearson Education, Inc.
Portal of Entry ID50
Botulinum 0.03 ng/kg
Shiga toxin 250 ng/kg
Staphylococcal enterotoxin 1350 ng/kg
Toxins
© 2013 Pearson Education, Inc.
Adherence
Adhesins/ligands bind to receptors on host cells Glycocalyx: Streptococcus mutans Fimbriae: Escherichia coli M protein: Streptococcus pyogenes
Form biofilms
© 2013 Pearson Education, Inc.
Figure 15.1a Adherence.
Surface molecules on a pathogen, called adhesins or ligands, bind specifically to complementary surface receptors on cells of certain host tissues.
Adhesin (ligand)
Hostcell
surface
Receptor
Pathogen
© 2013 Pearson Education, Inc.
Figure 15.1b-c Adherence.
E. coli bacteria (yellow-green) on human urinary bladder cells
Bacteria (purple) adhering to human skin
© 2013 Pearson Education, Inc.
Capsules
Prevent phagocytosis Streptococcus pneumoniae Haemophilus influenzae Bacillus anthracis
© 2013 Pearson Education, Inc.
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
© 2013 Pearson Education, Inc.
Enzymes
Coagulase: coagulates fibrinogen Kinases: digest fibrin clots Hyaluronidase: hydrolyzes hyaluronic acid Collagenase: hydrolyzes collagen IgA proteases: destroy IgA antibodies
© 2013 Pearson Education, Inc.
Chapter 15, unnumbered figure A, p. 434.
Blocked coronary artery
© 2013 Pearson Education, Inc.
Chapter 15, unnumbered figure B, p. 434.
Necrotizing fasciitis
© 2013 Pearson Education, Inc.
Chapter 15, unnumbered figure C, p. 434.
Streptokinase
Plasminogen
Plasmin
Fibrinbreakdown
Bloodclot
Mechanism of streptokinase
© 2013 Pearson Education, Inc.
Figure 15.2 Salmonella entering intestinal epithelial cells as a result of ruffling.
Ruffling ofhost cell
plasmamembrane
Salmonellatyphimurium
© 2013 Pearson Education, Inc.
Figure 22.16 How trypanosomes evade the immune system.
Weeks after infection
Rel
ativ
e n
um
ber
of
tryp
ano
som
es
1 2 3 40
Clone A Clone B Clone C
© 2013 Pearson Education, Inc.
Invasins Salmonella alters host actin to enter a host cell
Use actin to move from one cell to the next Listeria
Penetration into the Host Cell Cytoskeleton
© 2013 Pearson Education, Inc.
Figure 21.12 Cold sores, or fever blisters, caused by herpes simplex virus.
© 2013 Pearson Education, Inc.
Figure 15.3 Structure of enterobactin, one type of bacterial siderophore.
© 2013 Pearson Education, Inc.
Direct Damage
Disrupt host cell function Produce waste products Toxins
ANIMATION Virulence Factors: Enteric Pathogens
ANIMATION Virulence Factors: Penetrating Host Tissues
© 2013 Pearson Education, Inc.
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
© 2013 Pearson Education, Inc.
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.
exotoxins endotoxins
Cell wall
Exotoxin: toxicsubstances releasedoutside the cell
Clostridium botulinum, an example of a gram-positive bacterium thatproduces exotoxins
Endotoxins: toxinscomposed of lipidsthat are part of thecell membrane
Salmonella typhimurium, an example of a gram-negative bacterium that produces endotoxins
© 2013 Pearson Education, Inc.
Exotoxins
Specific for a structure or function in host cell
ANIMATION Virulence Factors: Exotoxins
© 2013 Pearson Education, Inc.
Figure 15.5 The action of an A-B exotoxin.
Bacteriumproduces andreleases exotoxin.
B (binding)component ofexotoxin attachesto host cellreceptor.
A-B exotoxinenters host cellby receptor-mediatedendocytosis.
A-B exotoxinenclosed inpinched-offportion of plasmamembrane duringpinocytosis.
A-B components ofexotoxin separate.The A componentalters cell functionby inhibitingprotein synthesis.The B componentis released fromthe host cell.
DNA
ExotoxinmRNA
Exotoxinpolypeptides
A (active)
B (binding)
A
B
A
B
A
B
A
B
A
B
B
B
A
Bacterium
Receptor
Plasmamembrane
Nucleus
Cytoplasm
Host cell
Protein
1
2
3
4
5
© 2013 Pearson Education, Inc.
Membrane-Disrupting Toxins
Lyse host’s cells by Making protein channels in the plasma
membrane– Leukocidins– Hemolysins– Streptolysins
Disrupting phospholipid bilayer
© 2013 Pearson Education, Inc.
Superantigens
Cause an intense immune response due to release of cytokines from host cells
Symptoms: fever, nausea, vomiting, diarrhea, shock, and death
© 2013 Pearson Education, Inc.
Exotoxin
Source Mostly gram-positive
Relation to microbe By-products of growing cell
Chemistry Protein
Fever? No
Neutralized by antitoxin? Yes
LD50Small
© 2013 Pearson Education, Inc.
Exotoxin Lysogeny
Corynebacterium diphtheriae
A-B toxin +
Streptococcus pyogenes
Membrane-disrupting erythrogenic toxin
+
Clostridium botulinum A-B toxin; neurotoxin +
C. tetani A-B toxin; neurotoxin
Vibrio cholerae A-B toxin; enterotoxin +
Staphylococcus aureus
Superantigen +
Exotoxins and Lysogenic Conversion
© 2013 Pearson Education, Inc.
Source Gram-negative
Relation to Microbe Outer membrane
Chemistry Lipid A
Fever? Yes
Neutralized by Antitoxin? No
LD50 Relatively large
Endotoxins
© 2013 Pearson Education, Inc.
Figure 15.6 Endotoxins and the pyrogenic response.
A macrophage ingestsa gram-negative bacterium.
The bacterium isdegraded in a vacuole, releasing endotoxinsthat induce the macrophage toproduce cytokines IL-1 and TNF-.
The cytokines arereleased into the bloodstream by the macrophages,through which they travel to the hypothalamus of the brain.
The cytokines induce the hypothalamus to produce prostaglandins,which reset the body’s“thermostat” to ahigher temperature,producing fever.
Nucleus
Macrophage
Endotoxin
Bacterium
Endotoxin
Cytokines
Vacuole
Bloodvessel
Hypothalamus of brainProstaglandin
Fever
Pituitarygland
1 2 3 4
© 2013 Pearson Education, Inc.
LAL Assay
Limulus amebocyte lysate assay Amebocyte lysis produces a clot Endotoxin causes lysis
ANIMATION Virulence Factors: Endotoxins
© 2013 Pearson Education, Inc.
Figure 15.7 Some cytopathic effects of viruses.
Inclusion body
Cytoplasmic mass
Nuclei
© 2013 Pearson Education, Inc.
Figure 15.8 Transformed cells in culture.
© 2013 Pearson Education, Inc.
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
© 2013 Pearson Education, Inc.
Pathogenic Properties of Fungi
Ergot toxin Claviceps
Aflatoxin Aspergillus
Mycotoxins Neurotoxins: phalloidin, amanitin
Amanita
© 2013 Pearson Education, Inc.
Pathogenic Properties of Protozoa
Presence of protozoa Protozoan waste products may cause symptoms Avoid host defenses by
Growing in phagocytes Antigenic variation
© 2013 Pearson Education, Inc.
Pathogenic Properties of Helminths
Use host tissue Presence of parasite interferes with host function Parasite’s metabolic waste can cause symptoms
© 2013 Pearson Education, Inc.
Pathogenic Properties of Algae
Paralytic shellfish poisoning Dinoflagellates Saxitoxin
© 2013 Pearson Education, Inc.
Figure 27.13 A red tide.
© 2013 Pearson Education, Inc.
Portals of Exit
Respiratory tract Coughing and sneezing
Gastrointestinal tract Feces and saliva
Genitourinary tract Urine and vaginal secretions
Skin Blood
Arthropods that bite; needles or syringes
© 2013 Pearson Education, Inc.
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.
portals of entry
penetrationor evasion ofhost defenses
damage tohost cells portals of exit
Mucous membranes• Respiratory tract• Gastrointestinal tract• Genitourinary tract• Conjunctiva
SkinParenteral route
CapsulesCell wall componentsEnzymesAntigenic variationInvasinsIntracellular growth
SiderophoresDirect damageToxins
• Exotoxins• Endotoxins
Lysogenic conversionCytopathic effects
Generally the same asthe portals of entry for agiven microbe:• Mucous membranes• Skin• Parenteral route
Number ofinvading microbes
Adherence
Clostridiumtetani
Mycobacteriumintracellulare
Micrographsare not shownto scale.
H1N1 flu virus