Introduction to Host-Microbe Interactions

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Introduction to Host-Microbe Interactions
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Normal Flora

• More bacterial than human cells in the body
• provide some nutrients (vitamin K)
• stimulate immune system, immunity can be
  cross-reactive against certain pathogens
• Prevent colonization by potential pathogens
  (antibiotic-associated colitis, Clostridium
  difficile)

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Potential Colonization Sites
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Types of Pathogens

• Primary Pathogens
• Cause disease upon infection, not normally
  associated with host
• Plague (Yersinia pestis), influenza virus
• Opportunistic Pathogens
• Cause disease under some circumstances, sometime
  members of normal flora
• Pseudomonas, Candida albicans

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Progression of Disease

• Transmission infectious dose from 10-106
  organisms
• Incubation period few days (common cold)-weeks
  (hepatitis A)-months (rabies)
• Convalescence
• Clearing (Strep throat, S. pyogenes)
• Latency (Chicken pox, tuberculosis, cold sores)

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Kochs Postulates

• Proposed by Robert Koch
• Conclude that a microbe causes a particular
  disease
• Must fulfill four postulates
• 1. Microorganism must be present in every case of
  the disease
• 2. Organism must be grown in pure culture from
  disease hosts
• 3. Produce the same disease from the pure culture
• 4. Organism recovered from experimentally
  infected hosts

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Molecular Postulates

• Describe virulence factors
• Four postulates
• 1. Virulence gene or its product must be present
• 2. Virulence gene must transform a non-pathogen
  into a pathogen
• 3. Virulence gene must be expressed during
  disease process
• 4. Antibodies against gene products are
  protective

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Establishing an Infection

• 1. Encounter
• fecal-oral (cholera)
• human-human (tuberculosis)
• animal-human (rabies)
• vector-borne (plague, lyme disease)
• environmental contact (anthrax)

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Establishing an Infection

• 2. Adherence
• Prevents early clearance
• Often bind host tissues via pili
• Specificity can determine host range of pathogen

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Establishing an Infection

• 3. Colonization multiplication and maintainance
• Competition with normal flora
• Resist
• bile
• stomach acid
• peristalsis
• skin secretions
• IgA (mucosal antibodies)
• compete with host for iron

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Establishing an Infection

• 4. Molecule Delivery
• Affects target cell structure and host response

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InvasionBreaching Anatomical Barriers

• Find new niche with few competitors
• Gain access to rich nutrient supply
• 1. Skin tough barrier, rely on wounds or
  insect vectors
• 2. Crossing mucous membrane (e.g. intestinal
  epithelial cells)

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Zippering-model of invasion

• Tight ligand-receptor interactions direct uptake
• one at a time uptake

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Ruffling method of invasion
General induced cellular response Can lead to
co-invasion of other bacteria in close proximity
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M cell Invasion

• M cells are a portal to the immune system
• Important site of antigen sampling
• Some pathogens use phagocytic nature of M cells
  to access deeper tissues by transcytosis

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Avoiding the Host Defenses

• 1. Hiding within host cells
• Avoid exposure to host antibodies if remain
  intracellular
• Access to rich source of nutrients

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Cell-to-cell Spreading
Shigella and Listeria species lyse out of
vacuole -assemble actin at pole -actin propels
them into neighboring cell convergent
evolution molecular mimicry
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Avoiding the Host Defenses

• 2. Avoiding complement killing
• Complement factors in blood serum can assemble
  into MAC membrane attach complex that are
  bactericidal
• C3b is first component of complex to bind
• Some bacteria bind factors that regulate C3b
  activity, prevent MAC assembly
• serum-resistance

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Avoiding the Host Defenses

• 3. Avoiding phagocytosis
• Innate immune cells engulf (phagocytose) and kill
  microorganisms with degradative enzymes
• Block signaling molecule production or degrade
  them after production
• C5a cleaved by C5a peptidase of Strep pyogenes
  (strep throat)

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Avoiding the Host Defenses

• 3. Avoiding phagocytosis
• Capsule production on surface of bacteria
  capsule leads to C3b inactivation-serum
  resistance
• M protein of Streptococcus also inactivates C3b
• Fc receptors bind antibodies and orient
  dangerous end away from bacteria
• Found in Streptococcus (Protein G) and
  Staphylococcus (Protein A)

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Survival Strategies within Phagocytes

• A niche without competitors
• Phagosomal escape lyse out of vacuole and grow
  in cytoplasm of host cell
• Shigella and Listeria

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Survival Strategies within Phagocytes

• Blocking lysosomal fusion prevent delivery of
  degradative enzymes to bacterial compartment
• Mycobacterium (tuberculosis)
• Salmonella (food poisoning or typhoid fever)
• Legionella (Legionnaires disease)

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Survival Strategies within Phagocytes

• Surviving lysosomal fusion
• Coxiella
• Legionella

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Avoiding Antibodies

• 1. IgA protease cleaves Abs found in mucosal
  secretions (Neisseria gonorrhoeae)
• 2. Antigenic variation turning pili On and Off,
  or switching to new pilus
• 3. Mimicking the host look like self-antigens
• Streptococcus pyogenes has capsule of hyaluronic
  acid, also made by host tissues

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Damage to Host (Disease)

• 1. Exotoxins
• May require prior colonization (cholera)
• May cause food poisoning even in absence of
  organism
• Botulism or Staphylococcus aureus toxin
• Immune system often target toxin for neutralizing
  Abs
• Vaccine against toxin
• A-B toxins A is catalytic subunit, B binds host
  cells

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Damage to Host (Disease)

• 2. Membrane-damaging toxins
• Hemolysins
• Cause cell-lysis Streptolysin O
• Phospholipases
• Cleave lipids in membranes Clostridium
  perfringens
• Gas gangrene

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Damage to Host (Disease)

• 3. Superantigens
• Hyperstimulate the immune system
• 1/5 T cells stimulated rather than 1/10,000
• Fever, nausea, diarrhea, vomiting
• Leads to shock
• Organ failure, circulatory collapse
• Cause of toxic shock syndrome (TSST)
• Staphylococcus aureus and Streptococcus pyogenes

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Damage to Host (Disease)

• 4. Endotoxins (attached to cell)
• LPS, in the outer leaflet of Gram negative
  bacteria
• Lipid A is toxic if organisms enter bloodstream
• Massive immune cell infiltration
• Activation of coagulation
• Intravenous fluids are screened for Lipid A

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Damage due to the Immune System

• Inflammation bacterial meningitis
• Neisseria meningitis
• Antigen-Ab complexes
• Settle in kidney or joints
• Glomerulonephritis from S. pyogenes
• Cross-reactive Abs
• Abs against pathogen may cross-react with host
  tissues
• Accute rheumatic fever, complication of Strep
  throat

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