module 9 pathogenicity - laulima...figure 15.9 microbial mechanisms of pathogenicity. when the...
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© 2013 Pearson Education, Inc.
Module 9 Pathogenicity
© 2013 Pearson Education, Inc. Lectures prepared by Christine L. Case
Chapter 15
Microbial Mechanisms of Pathogenicity
© 2013 Pearson Education, Inc. Lectures prepared by Helmut Kae
© 2013 Pearson Education, Inc.
Microbial Mechanisms of Pathogenicity
§ Pathogenicity: the ability of a pathogen to cause a disease by overcoming the defenses of the host
§ Virulence: the degree or extent of pathogenicity
§ A pathogenic organism is able to cause a disease § A pathogen that is highly virulent causes damaging
disease
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Portals of Entry
§ Portals of entry: avenues that pathogens can use to gain entry into the human body § Mucous membranes § Skin § Parenteral route
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Mucous membranes
§ Respiratory tract, gastrointestinal (GI) tract, genitourinary (GU) tract, conjunctiva
§ Most common portals are respiratory, GI tracts § Inhaled through mouth, nose § Eaten - most killed by acid, bile
§ GU tract is portal for pathogens that cause STDs
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Skin
§ Largest organ, first line of defense § Unbroken skin is impenetrable to most microbes
§ Some gain access through openings in skin § Some fungi can infect skin directly
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Parental Route
§ Access through breaks in skin § From cuts, bites, drying
§ All microbes have preferred portal of entry § Some microbes have multiple portals of entry
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Numbers of Invading Microbes
§ Likelihood of disease increases as number of pathogens increase § Too few can be overwhelmed by immune system
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Numbers of Invading Microbes
§ Virulence of a disease expressed as ID50: infectious dose for 50% of the test population
§ Expression of relative virulence under experimental conditions – can be different for different portals
§ Bacillus anthracis has 3 portals of entry
Portal of Entry ID50 Parenteral Route 10-50 endospores
Inhalation 10,000-20,000 endospores
Ingestion 250,000-1,000,000 endospores
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Numbers of Invading Microbes
§ Potency of toxin expressed as LD50: lethal dose for 50% of the test population
Toxin LD50 in mice Botulinum toxin 0.03 ng/kg
Shiga toxin 250 ng/kg
Staphylococcal enterotoxin 1350 ng/kg
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Virulence Factors
§ Structures of molecules that a pathogen uses to cause disease
§ Many different virulence factors exist
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Adherence
§ Means of attachment § Necessary for pathogenicity in most pathogens § Interfere with binding, interfere with infection
§ Adhesins (ligands) bind to complementary receptors § Adhesins may be located on glycocalyx, surface
structures § Adhesins usually glycoproteins, lipoproteins § Binding is specific for certain host tissues, receptors
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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)
Host cell
surface
Receptor
Pathogen
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How Pathogens Penetrate Host Defenses
§ Pathogens must penetrate tissue to cause disease § Several factors contribute to the ability of pathogens
to invade a host
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Capsules
§ Capsules impair phagocytosis (being eaten) § Prevents binding to pathogen § Capsules do not mean a bacterium is virulent
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Cell Wall Components
§ Some cell walls contain chemicals that contribute to virulence
§ 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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Antigenic Variation
§ During pathogenesis, body produces antibodies to fight infection § Bind to antigens on surface of bacteria
§ Antigenic variation: ability to alter surface antigen § Changes slowly over time
§ By the time body produces antibodies, surface antigen has changed
§ Influenzavirus, N. gonorrhoeae, Trypanosoma brucei (African sleeping sickness)
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How Bacterial Pathogens Damage Host Cells
§ Bacteria can damage host by: § Using host’s nutrients § Direct damage § The production of toxins
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Using Host’s Nutrients
§ Siderophores: proteins that tightly bind iron § Iron is required for growth
§ Iron in human body is tightly bound
§ Some pathogens release siderophores to take away iron
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Direct Damage
§ A number of ways that microbes can damage cells § Grow within cells, multiply and rupture cell § Attach to host cell and cause damage as pathogen uses
host for nutrients § Penetrate hosts by secreting enzymes
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Toxins
§ Toxins: poisonous substances that are produced by some microbes
§ Toxigenicity: ability of microbes to produce toxins § Two types of toxins
§ Endotoxins § Exotoxins
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Exotoxins
§ Exotoxins: protein toxins made inside bacterium and secreted to its surroundings
§ Many are enzymes, so small amounts harmful § Can act over and over again
Exotoxin: toxic substances released outside the cell
Clostridium botulinum, an example of a gram-positive bacterium that produces exotoxins
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Exotoxins
§ Soluble in body fluids, can be transported all over body
§ Diseases caused by bacteria that produce toxins are a direct result of toxin § Staphylococcal food poisoning is an intoxication
§ Antitoxins: antibodies produced by the body that provide immunity to toxins
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Types of exotoxins
§ A-B toxins: consist of two parts, “A” and “B”
§ A part is active (enzyme) component
§ B part is the binding component
§ Diptheria toxin is A-B toxin
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§ Lyse host cells by making protein channels in the plasma membrane – Leukocidins – Hemolysins – Streptolysins
§ Disrupts phospholipid bilayer
Membrane Disrupting Toxins
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Superantigens
§ Provoke very intense immune response § Stimulate proliferation (division) of T cells § Release chemicals, cytokines, that regulate immune
response § Too many cytokines in blood à fever, shock, death
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Endotoxins
§ Part of cell wall of gram-negative bacteria § LPS portion of outer membrane § Endotoxin is the lipid portion, called Lipid A
Exotoxins are proteins, Endotoxins are lipids
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Endotoxins
§ Endotoxins are released when Gram-negative bacteria die and cells lyse § Liberates endotoxins § Antibiotics can cause lysis à release LPS
Intact cell Dead cell
Endotoxins: toxins composed of lipids that are part of the cell membrane
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Endotoxins
§ All endotoxins produce the same signs and symptoms § Chills, fever, weakness, aches, shock, death § Disseminated intravascular clotting
§ Shock: life threatening drop in blood pressure § Endotoxic shock: shock produced by Gram-
negative bacterial endotoxin
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Endotoxins
Endotoxins cause fever (by inducing the release of cytokines) and shock
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Plasmids and Pathogenicity
§ R factors carry antibiotic resistance genes
§ Others can carry virulence factors § Toxins – tetanus neurotoxin, staphylococcal enterotoxin
§ Fimbriae, adhesins, enzymes (coagulase)
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Lysogeny and Pathogenicity
§ Prophage: phage DNA incorporated into bacterial chromosome
§ Prophage can provide new properties to bacteria
§ Lysogenic conversion: change in characteristics due to a prophage
§ Diptheria toxin, staphylococcal toxin, capsule of S. pneumoniae are encoded by prophages
§ Can transfer virulence genes to nonpathogenic strains
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Figure 13.12 The lysogenic cycle of bacteriophage λ in E. coli.
Phage DNA (double-stranded)
Bacterial chromosome
Occasionally, the prophage may excise from the bacterial chromosome by another recombination event, initiating a lytic cycle.
Lysogenic cycle
Cell lyses, releasing phage virions.
Lytic cycle
New phage DNA and proteins are synthesized and assembled into virions.
Prophage
Many cell divisions
Lysogenic bacterium reproduces normally.
4A
Phage attaches to host cell and injects DNA.
5
4B
3B Phage DNA integrates within the bacterial chromosome by recombination, becoming a prophage.
1
2
3A
Phage DNA circularizes and enters lytic cycle or lysogenic cycle.
OR
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Pathogenic Properties of Viruses
§ Viruses have a number of mechanisms to evade immune system § Can grow inside of host cells § Some can “hide” attachment sites - HIV has attachment sites too small for antibodies to
bind § Some attack immune cells - HIV
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Cytopathic Effects of Viruses
§ Cytopathic effects (CPE): visible effects of viral infection
§ CPE used to diagnose many viral infections
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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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Cytopathic Effects of Viruses
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Pathogenic Properties of Fungi
§ Fungal waste products may cause symptoms § Chronic infections provoke an allergic response
§ Tichothecene: toxins that inhibit protein synthesis § Fusarium, Stachybotrys
§ Proteases that modify host membranes, allow attachment § Candida, Trichophyton
§ Capsule prevents phagocytosis. § Cryptococcus
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Pathogenic Properties of Protozoa
§ Presence of protozoa and their waste products often produce symptoms
§ Some (Plasmodium) invade host cells (red blood cells)
§ Others (Giardia lamblia) attach to host cells by a “sucking disc” and digest cells and tissue
§ Some undergo antigenic variation (Giardia, Trypanosomas)
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Pathogenic Properties of Helminths
§ Presence of helminths causes disease § Interferes with host function
§ Some (Wuchereria bancrofti) use host tissues for growth, reproduction (elephantitis) § Block lymphatic circulation, leads to accumulation of
lymph, grotesque swelling
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Pathogenic Properties of Algae
§ Some produce neurotoxins § Paralytic shellfish poisoning
§ Alexandrium, a dinoflagellate
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Portals of Exit
§ Specific route that microbes use to leave the body § In secretions, excretions, discharges, tissue that’s been
shed
§ In general, portals of exit are related to infected tissue
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§ Respiratory tract § Coughing and sneezing
§ Gastrointestinal tract § Feces and saliva
§ Genitourinary tract § Urine and vaginal secretions
§ Skin § Blood
§ Arthropods that bite; needles or syringes
Portals of Exit
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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.
portals of entry
penetration or evasion of host defenses
damage to host cells portals of exit
Mucous membranes • Respiratory tract • Gastrointestinal tract • Genitourinary tract • Conjunctiva
Skin Parenteral route
Capsules Cell wall components Enzymes Antigenic variation Invasins Intracellular growth
Siderophores Direct damage Toxins
• Exotoxins • Endotoxins
Lysogenic conversion Cytopathic effects
Generally the same as the portals of entry for a given microbe: • Mucous membranes • Skin • Parenteral route
Number of invading microbes
Adherence
Clostridium tetani
Mycobacterium intracellulare
Micrographs are not shown to scale.
H1N1 flu virus