Lecture 20 Mechanisms of Pathogenicity Flashcards
What is a Virulence factor or Determinant?
Genetic, biochemical, structural features that contribute to virulence
Pathogenicity Islands
Large DNA regions that encode virulence factors
Describe “Viral Attachment” and name some examples
- Capsid and envelope spike proteins mediate attachment
- Ex
- GP120 of HIV, binds CD4 and CCR5
- Hemagglutinin of nfluenza binds sialic acid
- SARS -CoV-2 binds ACE2
Viral Spread
-Viruses can spread via blood, neuronal or lymphatic systems
Tropism
- cell, tissue, organ specificity
- determined by host cell receptor
How do viruses evade the “Innate Immune Response”?
- Capsules - block complement opsonization and membrane attack complex
- Proteases - degrade C3h (opsonin) or C5a (chemotactic factor)
How do viruses evade the “Adaptive Immune Response”?
- block antigen processing, MHC export
- Evade antibody -Antigenic Variation
- Amino acid changes in virion spikes (common in RNA viruses)
- Change cell surface outer membrane or pilli proteins
-Capsules - block antibody binding IgA proteases - enzymes that degrade IgA in secretions
What are some examples of Bacterial attachment
- Streptococcus pneumoniae
- Haemophilus influenzae
- Neisseria meningitidis
- Pseudomonas aeruginosa strains, called mucoid strains, make capsules
- opportunistic pathogen in burn and cystic fibrosis patients.
Coagulase
Bacterial Virulence Determinant for Invasion - clots fibrinogen in plasma, clot protects pathogen.
Streptokinase
Bacterial Virulence Determinant for Invasion -activates plasmin, digests fibrin clots - pathogen moves from clotted area
IgA proteases
Bacterial Virulence Determinant for Invasion - destroy antibody
Hemolysins
Bacterial Virulence Determinant for Invasion - digest RBCs, releases iron
Siderophores
Bacterial Virulence Determinant for Invasion - released, bind iron
Dnase
Bacterial Virulence Determinant for Invasion - lowers viscosity of secretions, spread
Bacteremia
Bacterial Virulence Determinant for Invasion - spread can lead to the presence of bacteria in the bloodstream
Name the Intracellular Bacterial Pathogen described in lecture
Listeria monocytogenes
- Gram +, food-borne pathogen
- Produce, raw (unpasteurized) milk, cheese, deli meat
- Psychrophile
- Can cross placenta
- Actin tail to move around inside the cell.
Bacterial Intracellular Pathogens example
- Chlamydia
- Legionella
- Mycobacterium tuberculosis
- Salmonella
Recall some examples of Bacteria evading innate and adaptive immunity by forming biofilms
- Streptococcus pneumoniae - Otitis Media (infection of middle ear)
- Pseudomonas in Cystic Fibrosis lung
- Staphylococcus and Enterococcus on heart valves - endocarditis
- Streptococcus mutans (and other bacteria) - dental plaque
Membrane - Disrupting Exotoxins
- Pore - forming exotoxins
- Leukocidins
- Hemolysins
Superantigens
Protein released by pathogen
- Cause T cells (>30%) to overexpress, release cystokines
- Failure of multiple host organs
-Toxic Shock
Syndrome - cause by Staphylococcus aureus superantigen
AB Extoxins
- Two subunits
- A - toxic effect
- B - binds target cell receptor
- Many AB toxins are ADP - ribosyltransferases
- Remove ADP - ribose group from NAD and attach t to a host cell protein.
- Host cell protein inactivated or functions abnormally
Diphtheria toxin - Corynebacterium diphtheriae
Binds growth factor receptor
Enters by endocytosis
ADP - ribosyl transferase
Attaches ADP ribose from NAD onto EF - 2
Host site specific AB toxins
Cholera toxin
- Produced by Vibrio Cholerae
- Enterotoxin
- ADP - ribosyltransferase
Botulinum toxin
-Produced by Clostridium botulinum
-Neurotoxin
-
Cholera Toxin
- A subunit ADP - ribosylates host G protein
- G protein activates Adenylarte Cylase enzyme
- Increased cAMP activates Chloride Channel
- Cystic Fibrosis Transmembrane Conductance Regulator
- Chloride out
- Sodium and water out
- Profuse watery diarrhea
