The pathogenesis of bacterial infections

Question 1

What is pathogenesis?

Answer 1

• all the cellular events leading to the development of disease
• bacterial pathogenesis - includes bacterial and host factor and interactions

Question 2

Are all bacteria pathogenic?

Answer 2

• no

Question 3

What is disease development dependent on?

Answer 3

Question 4

What is a pathogen?

Answer 4

• an organism with the ability to cause disease (damage the host)

Question 5

Who are important people who lead to discovery of bacteria etc?

Answer 5

• antoine van leeuwenhoek
• Pasteur and Henle - Germ Theory of Infectious Disease
• Koch - 1884/1890

Question 6

What are Koch’s postulates?

Answer 6

1. the organism must be reguarly associated with the disease and its characteristic lesions
2. the organism must be isolated from the diseased host and grown in culture
3. the organism must reproduce when a pure culture of the organism is introduced to a healthy, susceptible host
4. the organism must be re-isolated from the experimentally infected host

Question 7

What causes peptic ulcer disease?

Answer 7

• H.pylori (85-95%)
• depends on strain and host characteristics + conditions

Question 8

What are the weaknesses of Koch’s postulates?

Answer 8

• some agents cant be grown in culture
• some agents are present is sick and healthy hosts (opportunistic infections by commensals)
• no animal model for experimental infection
• no characteristic lesions
• multi-factorial diseases
• epidemiology - possible to establish role of pathogen as cause of disease, even if the 3 postulates cannot be proven

Question 9

Why are infections not in all hosts?

Answer 9

• infection depends on host factors / genetics
• some organisms have different genomes that affect different hosts
• need to have exposure to have chance of transmission

Question 10

What is pathogenicity?

Answer 10

• ability to cause disease

Question 11

What is virulence?

Answer 11

• degree of pathology caused by organism

Question 12

What is infectivity?

Answer 12

• the capacity of the organism for transmission/ spreading to new hosts

Question 13

What affects the infectivity?

Answer 13

• type of pathogen
  
  • mode of infection
  • strain, species
  • survival
• dosage
  
  • stage of growth
  • e.g. log phase - not as infective as focused on growing
• host factors
  
  • age, gender, immune status etc.
• environmental factors
  
  • temp, humidity, vector
• virulence
  
  • species, strain

Question 14

What affects transmissibility?

Answer 14

• capacity to grow in parts of the body
  
  • acute - short and fast
  • chronic - long and slow
• capacity to readily exit infected host
  
  • orifices
  • vectors
• capacity to survive in transit between hosts
  
  • enviro
  • sporulation

Question 15

What are exogenous and endogenous pathogens?

Answer 15

• exogenous - from outside, true pathogens, associated with disease only
• endogenous - commensal/ opportunistic - if get into wrong body compartment - persistent infections

Question 16

Whats the 5 step programme to becoming a successful bacterial pathogen?

Answer 16

• attach and enter the host body
• evade the host defence mechanisms (innate and adaptive)
• mutiply and spread - nutrients
• damage to host - direct and indirect through immune response
• transmission from one host to another healthy host

Question 17

How do bacterium reach a host?

Answer 17

• motility and taxis (directed motility)
• flagella - polymer of flagellin protein
• move towards nutrients and away from bile/ acid
• long - up to 20um - helical
• highly immunogenic - evolutionary conserved

Question 18

How do bacterial enter the host?

Answer 18

• skin/ extended mucosa - direct contact
• body orifices
  
  • repro tract
  • inhalation
  • ingestion
  • eyes/ ears
• injected into blood stream - arthropod borne
• environment, sporulation, reservoire host

Question 19

What are the body’s defences against pathogens?

Answer 19

• mucin/ mucus
• microflora - compete for nutrients
  
  • stomach - weak - 10^1 - 10^3
  • colon - strong - 10^10 - 10^11

Question 20

What are the bacterias strategies to invade?

Answer 20

• molecular mimicry
• switch off irritants
• hide inside ep/ immune cells
• prevention of activity of imm response e.g. release toxins

Question 21

What can the bacterium then choose to be?

Answer 21

• once theyve passed the dermal and mucin layers, and overcome the immune responses etc.
• have to choose whether to be IC or EC

Question 22

How do bacteria damage the host?

Answer 22

• lysis of host cells
• disruption of microflora
• disruption of immune system
• disruption of barrier function
• toxins:
  
  • endotoxins - non-proteinaceous - LPS/ lOS - fever markers
  • exotoxins - proteinaceous - proteolysis, neurological

Question 23

How does transmission occur?

Answer 23

• immune system responds to toxins
  
  • Pus produced - DNA, dead immune cells
  • spreading factors - proteins like DNases and proteases - facilitate spread into neighbouring tissues
• TB - coughing
• Anthrax - inhalation of spores
• E.coli - contaminated water
• vectors

Question 25

4 main issues for bacterial survival outside?

Answer 25

• nutrient availability
• lack of adherence sites and niches similar to hosts
• exposure to noxious chemicals/ predators
• exposure to sunlight and extreme weather

Question 26

What are the colonisation factors?

Answer 26

• adhesins - pilli
• bacterial motillity and chemotaxis - flagella
• enzymes that break down mucins and host tissues
• metabolism - use of specific nutrients

Question 27

What does invasiveness depend on?

Answer 27

• presence of capsules e.g. Bacullus anthracis, Pastreulla multocida, streptococcus pneumoniae)

Question 28

How are some bacteria resistant to phagocytosis?

Answer 28

• inhibit opsonisation
• kill the phagocytes
• live in the acidic enviro
• stop the lysosomes fusing with phagocytic vacuole
• use them as transport
• escape quickly

Question 29

What are exotoxins?

Answer 29

• produced mainly by G+ve bacteria/ some -ve e.g. E.coli
• proteins - few enzymes
• readily separated from bacteria by filtration
• fatal in small doses
• thermolabile
• cytopathic effects:
  
  • verotoxins - E.coli
  • haemolytic - staphylococci toxin
  • necrotis - tetanolysins
• immunogenic

Question 30

What is the role of Aggressins?

Answer 30

• contribute to the abiltiy of capsulate and non-capsulate bacteria to invade and multiply in hosts tissues
• enhance permeability of tissues - increase spread
  
  • hyaluronidase
  • coagulase
  • fibrinolysin/ kinase
  • depolymerising enzymes (lipases. proteases, nucleases)
  • deoxyribonuclease