Week 5: Infections and immunity II
Genetic variation of bacterial species
● When you look into genetics, proteomics and if you want to exchange data/materials
with other labs → you use a sequenced strain.
● When you look into vitro growth → do not go for sequenced strain → you are not
looking at the same pathogen over time.
● Subculturing: select against energetically costly structures, like flagella and protein
secretion.
● Continuous culturing of the M. Bovis → attenuation process (make it harmless for
people) → done for 11 years (230 passages) → but could have been done in 15
passages.
● Bacterial clonal line: mutation is passed on to the next daughter cell, but never mixed
between species.
● So, M. tuberculosis and M. Bovis are 99% identical but differ significantly from
pathogenic.
● Horizontal gene transfer: never mix the genome, only exchanging part of the
genome.
○ Transformation: free take up from the
environment. Extremely efficient, but not
all bacteria do this.
○ Transduction: phage-mediated transfer
between bacteria. For the phage DNA is
extremely efficient, but not for
chromosomal DNA is efficient.
○ Conjugation: tube between bacteria
exchanging part of the DNA. This is
plasmid-dependent, extremely efficient,
and chromosomal DNA transfer is
possible.
● Recombination required after transformation:
depends on the RecA protein and DNA
homology.
● Obligate pathogens have reduced their genome size: but, therefore need another
host to ensure their life cycle.
● Some species like H. pylori and N. meningitis have natural transformation.
How to determine horizontal gene transfer:
GC content (take into account amino acid composition), codon usage, and gene
order/synteny.
● Gene acquisition more frequent than gene replacement → housekeeping genes.
● HGT is more frequent between closely related strains/species.
● HGT is important for virulence.
Virulence plasmid = helps bacteria to infect humans by the production of mycolactone, which
is both cytotoxic and immunosuppressive. M. ulcerans.
Pathogenicity islands = virulence factor is shared because of HGT to non-pathogenic
species to make them pathogenic.
, Limits to HGT:
Gene acquisition will result in an increase in
genome size.
Genetic headroom = the amount of
dispensable information in the genome →
determines genetic variability and evolutionary
potential.
Significant loss of newly acquired genes.
Pan-genome = total gene pool of a species
Oncogenic micro-organisms
Humans cancer viruses: ~20% of all cancers
Virus Cancer DNA/RNA
EBV Burkitt’s lymphoma DNA
Nasopharyngeal carcinoma
Hepatitis B virus Hepatocellular carcinoma DNA
Hepatitis C virus Hepatocellular carcinoma DNA
HTLV-1 Adult T cell leukaemia ssRNA (retro)
HIV-1 (human immunodef.) Many tissues and organs ssRNA (retro)
HPV Cervical, penile, anogenital, head and DNA
neck
Kapsoni sarcoma herpes Kapsoni sarcoma DNA
Merkel cell polyoma Merkel cell carcinoma DNA
Transformation and oncogenesis are not required for viral replication.
Proto-oncogenes = activate cell cycle. MYC, and RAS are examples.
The cell cycle:
Rb = tumour suppressor gene.
Mode of action: checkpoints in the cell
cycle = restriction point.
MYC-c activates Cyclin D1 → Rb inhibits
E2F → Rb gets phosphorylated → E2F
gets activated → can enter the S-phase
in the cell cycle.
P53 & P21 = tumour suppressor genes.
Upon stress → no Cyclin D → no
phosphorylation of Rb → no entry into
the cell cycle.
Replication of the virus:
Genetic variation of bacterial species
● When you look into genetics, proteomics and if you want to exchange data/materials
with other labs → you use a sequenced strain.
● When you look into vitro growth → do not go for sequenced strain → you are not
looking at the same pathogen over time.
● Subculturing: select against energetically costly structures, like flagella and protein
secretion.
● Continuous culturing of the M. Bovis → attenuation process (make it harmless for
people) → done for 11 years (230 passages) → but could have been done in 15
passages.
● Bacterial clonal line: mutation is passed on to the next daughter cell, but never mixed
between species.
● So, M. tuberculosis and M. Bovis are 99% identical but differ significantly from
pathogenic.
● Horizontal gene transfer: never mix the genome, only exchanging part of the
genome.
○ Transformation: free take up from the
environment. Extremely efficient, but not
all bacteria do this.
○ Transduction: phage-mediated transfer
between bacteria. For the phage DNA is
extremely efficient, but not for
chromosomal DNA is efficient.
○ Conjugation: tube between bacteria
exchanging part of the DNA. This is
plasmid-dependent, extremely efficient,
and chromosomal DNA transfer is
possible.
● Recombination required after transformation:
depends on the RecA protein and DNA
homology.
● Obligate pathogens have reduced their genome size: but, therefore need another
host to ensure their life cycle.
● Some species like H. pylori and N. meningitis have natural transformation.
How to determine horizontal gene transfer:
GC content (take into account amino acid composition), codon usage, and gene
order/synteny.
● Gene acquisition more frequent than gene replacement → housekeeping genes.
● HGT is more frequent between closely related strains/species.
● HGT is important for virulence.
Virulence plasmid = helps bacteria to infect humans by the production of mycolactone, which
is both cytotoxic and immunosuppressive. M. ulcerans.
Pathogenicity islands = virulence factor is shared because of HGT to non-pathogenic
species to make them pathogenic.
, Limits to HGT:
Gene acquisition will result in an increase in
genome size.
Genetic headroom = the amount of
dispensable information in the genome →
determines genetic variability and evolutionary
potential.
Significant loss of newly acquired genes.
Pan-genome = total gene pool of a species
Oncogenic micro-organisms
Humans cancer viruses: ~20% of all cancers
Virus Cancer DNA/RNA
EBV Burkitt’s lymphoma DNA
Nasopharyngeal carcinoma
Hepatitis B virus Hepatocellular carcinoma DNA
Hepatitis C virus Hepatocellular carcinoma DNA
HTLV-1 Adult T cell leukaemia ssRNA (retro)
HIV-1 (human immunodef.) Many tissues and organs ssRNA (retro)
HPV Cervical, penile, anogenital, head and DNA
neck
Kapsoni sarcoma herpes Kapsoni sarcoma DNA
Merkel cell polyoma Merkel cell carcinoma DNA
Transformation and oncogenesis are not required for viral replication.
Proto-oncogenes = activate cell cycle. MYC, and RAS are examples.
The cell cycle:
Rb = tumour suppressor gene.
Mode of action: checkpoints in the cell
cycle = restriction point.
MYC-c activates Cyclin D1 → Rb inhibits
E2F → Rb gets phosphorylated → E2F
gets activated → can enter the S-phase
in the cell cycle.
P53 & P21 = tumour suppressor genes.
Upon stress → no Cyclin D → no
phosphorylation of Rb → no entry into
the cell cycle.
Replication of the virus:
