transmission routes of infectious diseases

Question 1

bacterial pathogens

Answer 1

• easy to study for adaptations
• horizontal gene transfer
• new enviornments already colonised by other adapted bacteria provide a source of genetic material
  
  • microbiome
  • rapid adaptation

Question 2

horizontal gene transfer

Answer 2

• transformation
  
  • uptake of naked DNA from enviornment by competent cells
• transduction
  
  • genetic material transferred by phage
  • closely related organisms - need specific phage receptors
• conjugation
  
  • direct transfer of DNA by physical interaction
  • plasmids or transposons
  • can be distantly related bacteria

Question 3

modes of disease transmission

Answer 3

• direct
• water-borne
• vector-borne
• sit-and-wait

Question 4

direct transmission

Answer 4

• person-to-person contact
• trade-off between virulence and transmission
  
  • transmission relies on host mobility
  • kill host → compromise mobility
• e.g. bacterial and viral STIs

Question 5

STIs

Answer 5

• host must feel well enough and be attractive enough to engage in sexual intercourse
• pathogen must remain transmissible until change of sexual aprtner
• initially low levels of virulence that later increase

Question 6

bacterial STIs

Answer 6

• chlamydia, gonorrhea
• often asymptomatic for months/years
• infections usually restricted to mucosal tissues
• avoid damage to cells critical to host health
• immune evasion mechanisms
• long term consequences after transmission

Question 7

viral STIs

Answer 7

• HSV, HIV
• target immune-privileged tissues
  
  • nervous system - avoid detection
• usually latent
  
  • incorporate into host genome and remain silent until immune response is over
  • then make new virus particles
• not usually virulent (except HIV)

Question 8

HIV

Answer 8

• very virulent, but later on
• loss of Nef gene
  
  • found in monkey SIV (doesn’t cause AIDS)
• product suppresses T-cell activation and activation-induced cell death

Question 9

water-borne transmission

Answer 9

• doesn’t rely on host mobility
• more virulent
• e.g. cholera

Question 10

cholera

Answer 10

• Vibrio cholerae
• aquatic bacterium, many serotypes
  
  • 2 are toxigenic (O1, O139)
• fecal-oral route
• colonise intestine and rapidly proliferate
• fulminant diarrhoea
  
  • up to 10^7 bacteria/ml
• dilution in water supply menas high numbers necessary
  
  • also high susceptibility to stomach acid
• virulence from use of host resources for proliferation nutrients

Question 11

V. cholerae competence regulon

Answer 11

• TfoX
• set of genes important for survival in natural environment
• outside host, Vibrio associates with marine zooplankton
  
  • feeds on exoskeletal chitin
  • growth to high numbers
• regulon expressed at high numbers
• induces other genes to be expressed
  
  • T6SS type IV secretion system

Question 12

T6SS type IV secretion system

Answer 12

• gene encodes a spear
• stabs unrelated bacteria without secretion system
  
  • release DNA into medium
  • picked up by competent cells
• other TfoX regulon components facilitate HGT
• huge genetic diversity generated

Question 13

TCP

Answer 13

• toxin co-regulated pilus
• V. cholerae use to latch on to zooplankton exoskeleton and feed
• hair-like projection
• facilitates attachment to human intestinal epithelium for colonisation
• also receptor for CTX phage transduction

Question 14

CTX

Answer 14

• cholera toxin
• encoded by genome of CTX phage
• enters bacteria by transduction
• A and B subunits push up against membrane

Question 15

A and B subunits of CTX

Answer 15

• B binds membrane proteins → channel forms
• A pushed through channel
  
  • alters GPCR signalling transduction
  • intracellular cAMP increase
• chloride floods out into intestinal lumen
  
  • prevent Na+ uptake into intestinal cells
• osmotic imbalance
• water floods out from cells to lumen

Question 16

CTX phage

Answer 16

• hijakcs bacteria to replicate itself
  
  • causes bacteria to hijack host
• V. cholerae would be harmless without CTX phage
• all bacteria released from host are infected with phage
• converts environmental strains to become toxigenic and contain CTX phage

Question 17

vector-borne transmission

Answer 17

• little reliance on host mobility → increased virulence
  
  • but need to consider vector competence
• e.g. plague

Question 18

plague

Answer 18

• Yersinia pestis
• Yersinia:
  
  • mammalian gut bacteria, not usually virulent
  • fecal oral transmission
• Y. pestis - highly virulent in humans and rodents (rats)
  
  • diverged 1500-20,000 years ago
  • transmitted by fleas
  • epizootic outbreaks → transmission to humans
    
    • not enough rats
• black plague - 30-60% of europe dead

Question 19

acquired genetic elements of Y. pestis

Answer 19

• allowed bacteria to overcome infection barriers
  
  • pYv
  • pFra
  • hms
  • pPst

Question 20

pYv

Answer 20

• plasmid encoing type III secretion system injectisome proteins
• impair host immunity
• inject effectors into host macrophages
• allows transmission from gut to bloodstream
  
  • essential for transmission to fleas

Question 21

pFra

Answer 21

• plasmid encoding Yersinia murine toxin
• protects against antibacterial agents in flea midgut

Question 22

hms

Answer 22

• gene products block flea digestive tract
  
  • form biofilm in flea oesophagus
• flea bites rat → uptake of blood
• blood mixes with bacteria and vomited back up
• infects rat at bite site
• blocks feeding → rats always hungry → keep feeding

Question 23

pPst

Answer 23

• plasmid gained through conjugation
• encodes plasminogen activator pla
  
  • allows bacterial hijack of host and dissemination
• escapes from macrophage in lymph node
• rapid proliferation
• creates buboes at lymph nodes

Question 24

causes of Y. pestis virulence

Answer 24

• poor vector competence
  
  • high levels of bacteremia needed to infect flee
  • needs massive host exploitation to create this
• high vector density
  
  • rats covered with fleas most of the time
  • bacteria transmitted to vector even if host dies quickly
• host-seeking behaviour of vector
  
  • fleas don’t leave host
  • host death encourage host-seeking
  • epizootic outbreaks
• zoonosis
  
  • humans not preferred host
  • lack of co-adaptation

Question 25

sit-and-wait transmission

Answer 25

• pathogens exit host and wait for uninfected host’s arrival
• relies on uninfected host’s mobility
• requires survival in external environment for long time
• more bacteria in infected host → greater chance of ne whost infection → use all possible resources
• e.g. anthrax

Question 26

anthrax

Answer 26

• bacillus anthracis
• soil bacteria
• form durable dormant spores
• wait for decades/centuries
• picked up through cuts, breathing, ingestion

Question 27

anthrax spores

Answer 27

• highy resistant to host immune system even if recognised
• germinate and become metabolically active
• rapid replication to take over host
• 10^8 bacteria per ml of host blood
• kill host so it bleeds out
• bacteria can escape and sporulate to be picked up by another organism

Question 28

barriers and solution to anthrax transmission

Answer 28

• prolonged survival in environment
  
  • produce spores
• host immune system
  
  • capsule prevetning phagocytosis
  • toxins to destroy host immune system

Question 29

anthrax virulence

Answer 29

• determined by copy numbers of 2 plasmids
  
  • pXO1
  • pXO2

Question 30

pXO1

Answer 30

• produces exotoxins
• oedema toxin
  
  • increase cellular cAMP
  • osmotic imbalance → oedema (blood-filled swelling)
• lethal toxin
  
  • stimulates cytokine release by macrophages
  • shock and death
  • oedema haemorrhage → bacterial spill out
• toxin cooperation to suppress host immune repsonses

Question 31

pXO2

Answer 31

• produces capsule proteins
  
  • exterior coat of vegetative cells
  • inhbiits phagocytosis by host immune system