Disease emergence

Question 1

Comparing genomes of pathogens

• compare with…?
• look at?

Answer 1

Compare w/ ancestors

Compare w/ related non-pathogens

Look at genomic changes + different phenotypes

Question 2

Genomic islands

Answer 2

large regions of DNA present in some strains BUT not others

can encode pathogenesis functions

evidence of HGT

Question 3

How can you tell if a genomic island is adaptive (i.e. confers virulence)?

Answer 3

> Functional homology
= genes present in pathogenic strains but absent in closely-related non-pathogenic strains
e.g. PAIs

> Convergent evolution
(homoplasy)

Question 4

PAIs

- features

Answer 4

Differ from core GC content
(HGT?)

Flanked by small direct repeats
(Recombination)
(Can aid insertion into host genome)

Contain mobility genes
(Can –> instability)

Mosaic structure

Can be plasmid borne

Question 5

PAIs

- e.g. B. pertussis O-antigen

Answer 5

= component of LPS

• important Gram -ve factor that protects against innate response,
  blocks Ab binding,
  protects against envrio stresses e.g ABs

Genomic region has low GC content
= HGT?

Question 6

PAIs

• Phage derived e.g.
• Plasmid derived e.g.

Answer 6

Cholera toxin

B. anthracis

Question 7

Helicobacter pylori

- prevalence

Answer 7

Infection occurs worldwide
- prevalence depends on country + population groups
(- correlates with socio-economic conditions
80% in developing countries, 20% developed)

Question 8

Helicobacter pylori

Answer 8

Acquisition
- ingestion of bacterium

Transmission
- within families in early childhood
(NOT isolated form water etc)

Question 9

CagA

• encoded where?
• in strains from where?
• encodes?

Answer 9

= cytotoxin-associated gene A
- on Cag PAI

• found in almost all strains from East Asia
• a T4SS
• > injects CagA into target cell
• > CagA localises to inner surface of cell membrane
• > undergoes tyrosine phosphorylation by Src-family kinases

Question 10

CagA

- in cancer

Answer 10

Phosphorylated CagA interacts w/ SHP-2 tyrosine phosphatase
= functionally active

-> triggers host cell morphological change to motile phenotype
= ‘hummingbird phenotype’

• associated w/ cancer (metastasis)

Question 11

H.pylori pathogenesis

- Genome changes continuously and produces…?

Answer 11

> Hop proteins
= Adhesions

> Ure1
= pH-gated urea channel

> CagA
= phosphorylated
-> binds to SHP-2 tyrosine phosphatase
= GF-like response

Question 12

Strongest way you can identify adaptation in a genome w/out doing experiments?

Answer 12

Homoplasy

• if 2+ independent lineages have acquired the same DNA sequence
  and then have the same trait
  = can be fairly certain of the gene’s function

Question 13

S. aureus in poultry

- paper

Answer 13

Murray et. al (2017)

• characterised genetic variation in population of genome-sequenced S. aureus isolates of poultry and human origin

Question 14

S. aureus in poultry

- paper findings

Answer 14

CC5 = dominated poultry-associated sequence cluster

Poultry + human CC5 isolates significantly distinct

More recombination events in poultry

Evidence of adaptation, following human-to-poultry host transition