Lecture 18: Trickery of Bacterial Pathogens

Question 1

What are the human-microbe relationships?

Answer 1

1. Colonization of human host
   a. either as part of gut flora or harmony
   with the host
   b. or subverting host defences,
   causing disease
2. Few microbes can invade tissues &
   prod toxic substances/inflict damage

Question 2

Explain the production/delivery of various harmful factors?

Answer 2

1. Organism needs to attach to hose tissue
2. Need to replicate and evade immunity
3. Damage host tissues to escape

Question 3

What is the process of disease?

Answer 3

1. Microbes cause disease whilst stealing:
   a. space
   b. nutrients
   c. and/or living tissue from host (e.g., us)
2. How do they do this?
   a. Gain access to host (‘contamination’)
   b. Adhere to host (‘adherence’)
   c. Replicate on host (‘colonization’)
   d. Invade tissues (‘invasion’)
   e. Production of toxins, proteins, or other
   agents that cause host harm (‘damage’)

Question 4

What are the 4 main mechanisms of bacterial pathogenicity? Give examples.

Answer 4

1. Toxin ingestion following production
   a. Bacillus cereus
   b. not ingesting the pathogen, just its
   toxin
   c. sometimes associated with food
   poisoning
2. Toxin production following
   colonization
   a. Clostridium botulinum
3. Invasion of host tissues without toxin
   production
   a. Mycobacterium tuberculosis
4. Tissue invasion followed by toxin
   production
   a. Vibrio cholerae

Question 5

How do we know if a pathogen causes a specific disease?

Answer 5

1. Robert Koch
   a. founder of public health
   b. developed koch’s postulates
2. In 1800’s, discovered:
   a. Tuberculosis = Mycobacterium
   tuberculosis
   b. Cholera = Vibrio cholerae
   c. Anthrax = Bacillus anthracis

Question 6

What must bacteria do for successful infection?

Answer 6

1. Sense environment
   a. sense they’re inside the human host
   e.g., sensing the temperature (37)
2. Need to know where they are…
3. must express proteins to survive stress
4. must express proteins required for
   adhesion or invasion
5. May make toxins
6. May enter host cell and replicate
7. May spread through host cells

Question 7

what is the ‘course’ of an infectious disease?

Answer 7

1. Incubation period: interval between
   exposure and illness onset
2. Illness phase: may still be infectious
   during incubation or convalescence
   phases
3. Covalence phase: time of recuperation
   and recovery from illness

Question 8

What are the principles of infectious disease/pathogenicity?

Answer 8

1. Primary pathogen: microbe or virus that
   causes disease in healthy individual.
   a. E.g., plague, malaria, measles
2. Opportunistic pathogen: causes disease
   only when body’s innate or adaptive
   defences are compromised or when
   introduced into unusual location
   a. Can be members of normal microbiota
   or common in environment
   (Pseudomonas)

Question 9

What is meant by virulence?

What is meant by virulence factors?

Answer 9

1. Refers to degree of pathogenicity

2. Allow microorganism to cause disease

Question 10

What are the common virulence factors?

Answer 10

1. Endotoxin
2. Capsule
3. Antigenic phase variation
4. Sequestration of growth factors
5. Resistance to serum killing
6. Antimicrobial resistance

Question 11

What are examples of virulence factors associated with specific pathogens?

Answer 11

1. Exotoxin production
2. Expression of adhesion factors
3. Intracellular survival and manipulation

Question 12

What is molecular Koch postulates

Answer 12

show that a gene found in a pathogenic microorganism encodes a product that contributes to the disease caused by the pathogen - virulence factor

   1. specific inactivation of gene(s) lead to 
      measurable loss in pathogenicity
   2. reintroducing gene should restore 
       pathogenicity
   3. gene causing virulence must be 
       expressed during infection
   4. immunity must be protective 
   5. phenotype or property under 
       investigation should be associated with 
       pathogenic members of genus

Question 13

What are fimbriae?

Answer 13

1. Key adherence factors
2. How do cells avoid physical &
   immunological removal?
   a. adhere to cell surfaces and ECM
   b. Solid surfaces (e.g., teeth, heart valves)
   c. Other bacteria
3. How do cells adhere?
   a. Often located at ends of fimbria or curli
   b. & other outer membrane proteins
4. Adherence often combined with
   manipulation of host cell signalling and
   cytoskeleton (salmonella
   a. Adherence
   b. invasion

Question 14

How do microorganisms scavenge iron?

Answer 14

1. free iron is low in bodily fluids (it is
   bound to other things)
2. Many different systems for
   scavenging:
   a. Siderophores chelate available iron
   & transport into bacteria
   b. scavenged direct from iron-binding
   proteins (e.g., lactoferrin-binding
   proteins)
   c. Often co-ordinately regulated
   d. Some pathogens avoid problem by
   cutting off need for iron (e.g.,
   Treponema pallidum - syphilis)
3. Low level iron switches on aggressive
   virulence factors
   a. Diphtheria toxin (controlled by DtxR
   repressor)
   b. Shiga-like toxin
   c. Pseudomonas aeruginosa exotoxin
   A

Question 15

How do microorganisms avoid phagocytosis?

Answer 15

1. Capsule around them - avoids

recognition by phagocyte

Question 16

How do pathogens damage the host?

Answer 16

1. Exotoxins: proteins with specific
   damaging effects
   a. secreted or leak into tissue following
   bacterial lysis - foodborne intoxication
   = consumption - destroyed by heating
   b. act locally or systernically
   c. Proteins, immune system can generate
   Ab’s

Question 17

What are different types of exotoxins?

Answer 17

1. Toxoids: inactivated toxins
2. Antitoxin: suspension of neutralising Ab’s
3. Neurotoxins: damage NS
4. Enterotoxins: cause intestinal
   disturbance
5. Cytotoxins: damage variety of cell types

Question 18

What are two parts of A-B toxins?

Answer 18

1. A = active subunit, toxic, usually an
   enzyme
2. B = binds to cell, determines affected
   cell type
   a. Structure of B subunit allows novel
   approaches for vaccines and therapies,
   can be used to deliver medically useful
   compounds to specific cell type

Question 19

What are endotoxins?

Answer 19

1. other bacteria cell wall components
2. Endotoxin: lipid A of LPS
3. Lipid A triggers inflammatory response
   a. when localized helps clear infection
   b. When systemic, widespread response -
   septic shock or endotoxic shock
4. lipid A released following cell lysis
5. activates innate and adaptive defences
   a. toll-like receptors induce cytokine
   production; T-independent antigen
   response of B-cells at high
   concentrations

Question 20

What do endotoxins do to the host?

Answer 20

1. fever
2. Hypotension
   a. life-threatening complication of septicaemia
   b. endotoxic shock seen with intraveous equipment
3. MOST EFFECTS OF ENDOTOXIN
   MEDIATED BY TUMOUR NECROSIS
   FACTOR

Question 21

What is EPEC

Answer 21

1. one of many categories of diarrheagenic
   E. coli
2. well established cause of human
   diarrhoea - particularly young children
3. Hallmark of EPEC is A/E histopathology,
   often observed in small bowel biopsy
   specimens from infected patients

Question 22

What changes in host cells once infected by EPEC

Answer 22

1. Formation of actin pedestals
2. localized actin accumulation is so
   distinct it is the basis of vitro
   diagnostic test for EPEC

Question 23

What are type-3 secretion systems

Answer 23

1. Essentially a needle
2. Five components:
   a. Regulators
   b. Chaperons
   c. Secretion apparatus
   d. Translocators
   e. Effectors
3. Five functions
   a. Export proteins across bacterial
   envelope
   b. Bring bacterial & host cells close
   together
   c. Translocate proteins between
   d. Translocated proteins across cell
   membranes
   e. Translocated proteins subvert host
   cell functions