Molecular Infection Biology
SHORT VERSION
AM_470657
P2 2021
AM_470657
Molecular Infection Biology Short version
,Inhoud
1.What is a pathogen? Symbiosis versus pathogenesis....................................................................................2
2.Which pathogen strain to use?......................................................................................................................4
3.What infection disease models?....................................................................................................................6
4.How to identify virulence factors?.................................................................................................................8
5.Virulence factors: Immune system interplay & Red queen hypothesis.......................................................11
6.Virulence factors: Adaptation in metabolism..............................................................................................13
7.Virulence factors: Intracellular trafficking & Survival...................................................................................15
8.Regulation of virulence factors....................................................................................................................17
9.Pathogens in the gut microflora: Clostridium difficile..................................................................................20
10.Molecular detection of novel viruses & Coronaviruses and coronavirus reinfections...............................22
11.Bacterial Vaccine Design............................................................................................................................24
1
, 1.What is a pathogen? Symbiosis versus pathogenesis
A pathogen is a microbiological agent that causes disease or illness to its host.
Microflora vs pathogens: can we make a distinction between the two.
Gut microflora: study the effects in gnotobiotic animal models. Animals without gut microflora:
Need 30% more calories gut microflora help with digestion of complex polymers.
Have underdeveloped villi and less vascularization
Have underdeveloped mucosal immune responses gut microflora induce the production of
antimicrobial peptides.
Problems with our microflora:
Wrong sites
Damage to epithelium cells: for instance infiltration from gut into peritoneum. Co-infection of E.
coli and B.fragilis has an synergistic effect causing abscess formation in the gut.
New sites for microflora:
E.coli in urinary tract causing
infections
Foreign bodies cause septic
shock in 1-5% of the
patients. The most common
pathogens are S. aureus and
S.epidermidis.
Wrong host: different
species have similar
composition, but are strain
specific.
Abnormalities in host defense
Genetic defects: they don’t need to be as severe as SCID. One example is the herpes simplex
encephalitis infection, caused by Alpha-herpesviridae.
Alpha-herpesviridae is a dsDNA virus, in which half of the population is chronically infected with one or
more HSV/VZV/EBV viruses. They reside in neuronal cells. They can reactivate and re-infect the peripheral
tissue cells or, in rare cases, cause herpes simplex encephalitis infection
(Acyclovir: drug that helps against sporadic viral encephalitis.)
People with reactivated herpes simplex encephalitis has an unlucky composition in the TLR receptors.
Normally:
o TLR3: dsRNA strands
o TLR7/8: ssRNA strands
o TLR9: unmethylated GpC regions in the DNA.
People turned out to contains a TLR3 pathway deficiency. TLR 3, normally, trigger the upregulation of type
1 interferons. Neighboring cells can sense interferon type 1 and turn into a proapoptotic state. When the
virus infects these cells, these cells will trigger apoptosis. This way the virus cannot replicate anymore. This
process is altered.
Suppression of immune responses: Measles/malaria could have severe outcomes upon
malnutrition. Also after transplantations you can get infections quickly, because they suppress the
immune system, so that they don’t attack the new organ.
Other infections: HIV destroys CD4+ cells: AIDS patients have opportunistic effects. Influenza A
damage the epithelial cells: most often bacterial infections cause mortality.
2
SHORT VERSION
AM_470657
P2 2021
AM_470657
Molecular Infection Biology Short version
,Inhoud
1.What is a pathogen? Symbiosis versus pathogenesis....................................................................................2
2.Which pathogen strain to use?......................................................................................................................4
3.What infection disease models?....................................................................................................................6
4.How to identify virulence factors?.................................................................................................................8
5.Virulence factors: Immune system interplay & Red queen hypothesis.......................................................11
6.Virulence factors: Adaptation in metabolism..............................................................................................13
7.Virulence factors: Intracellular trafficking & Survival...................................................................................15
8.Regulation of virulence factors....................................................................................................................17
9.Pathogens in the gut microflora: Clostridium difficile..................................................................................20
10.Molecular detection of novel viruses & Coronaviruses and coronavirus reinfections...............................22
11.Bacterial Vaccine Design............................................................................................................................24
1
, 1.What is a pathogen? Symbiosis versus pathogenesis
A pathogen is a microbiological agent that causes disease or illness to its host.
Microflora vs pathogens: can we make a distinction between the two.
Gut microflora: study the effects in gnotobiotic animal models. Animals without gut microflora:
Need 30% more calories gut microflora help with digestion of complex polymers.
Have underdeveloped villi and less vascularization
Have underdeveloped mucosal immune responses gut microflora induce the production of
antimicrobial peptides.
Problems with our microflora:
Wrong sites
Damage to epithelium cells: for instance infiltration from gut into peritoneum. Co-infection of E.
coli and B.fragilis has an synergistic effect causing abscess formation in the gut.
New sites for microflora:
E.coli in urinary tract causing
infections
Foreign bodies cause septic
shock in 1-5% of the
patients. The most common
pathogens are S. aureus and
S.epidermidis.
Wrong host: different
species have similar
composition, but are strain
specific.
Abnormalities in host defense
Genetic defects: they don’t need to be as severe as SCID. One example is the herpes simplex
encephalitis infection, caused by Alpha-herpesviridae.
Alpha-herpesviridae is a dsDNA virus, in which half of the population is chronically infected with one or
more HSV/VZV/EBV viruses. They reside in neuronal cells. They can reactivate and re-infect the peripheral
tissue cells or, in rare cases, cause herpes simplex encephalitis infection
(Acyclovir: drug that helps against sporadic viral encephalitis.)
People with reactivated herpes simplex encephalitis has an unlucky composition in the TLR receptors.
Normally:
o TLR3: dsRNA strands
o TLR7/8: ssRNA strands
o TLR9: unmethylated GpC regions in the DNA.
People turned out to contains a TLR3 pathway deficiency. TLR 3, normally, trigger the upregulation of type
1 interferons. Neighboring cells can sense interferon type 1 and turn into a proapoptotic state. When the
virus infects these cells, these cells will trigger apoptosis. This way the virus cannot replicate anymore. This
process is altered.
Suppression of immune responses: Measles/malaria could have severe outcomes upon
malnutrition. Also after transplantations you can get infections quickly, because they suppress the
immune system, so that they don’t attack the new organ.
Other infections: HIV destroys CD4+ cells: AIDS patients have opportunistic effects. Influenza A
damage the epithelial cells: most often bacterial infections cause mortality.
2
