INTRACELLULAR BACTERIA Flashcards
Which evidence supports a role of C. trachomatis as a cause of ovarian cancer?
There is epidemiological evidence for this affirmation. It persists for long times without causing symptoms. It induces DNA damage and manipulate oncogenic signalling. We are going to take a further look at that.
They manipulate Myc, Ras, PI3K, p53 to prevent the eradication and to get food.
- Cell-autonomous defense functions to prevent infection with intracellular bacteria. Name three different strategies and explain why they are particularly efficient against intracellular bacteria.
- upregulation of p53- it incuces cell cycle arrest and apoptosis which leads to destruction of cell infected by bacteria and the bacteria propagation is inhibited.
- proteosomal degradation and ubiquitination- causes the destrurction of intracellular bacteria using proteosomes.
- Cellular innate immune defence- Can phagocytose and destroy pathogens.
Obligate intracellular bacteria escape the host immune defense. Name four general mechanisms which are related to their obligate intracellular lifestyle.
a. Downregulation of major tumor suppressor p53 induced by Chlamydia infection.
This bacterium is connected to ovarian cancer. They have no interest to make cancer, there is no benefit for that, but they make it. We have damage because of the bacteria at the first place. p53 tries to overcome this damage, but unfortunately p53 downregulates metabolites, and the bacteria cannot tolerate this, so it induces the degradation of p53. The cell has now no mechanism to overcome this damage.
b. Proteosomal degradation and ubiquitination:
If something in the cell realises that this is foreign, they fight the inclusion by putting ubiquitin on the surface. They destruct or try to destroy the inclusion. But it has a mechanism to remove the ubiquitin that has been put on the surface of the inclusions. It secretes deubiquitinase Cdu1 into the inclusion membrane.
They can remove this very efficiently. That is what normally happens. If we take the mutant which cannot protect themselves (this is an infection model), the mutant cannot survive. We have continuous ubiquitination. When the bacteria leave, we have the cells there to fight the bacteria, they as well have to survive. Innate immune defence plays a role here as well. The most efficient way of how innate fights is by neutrophils. They have a way to sense the environment whether there are pathogens. They look for the bacteria.
c. Cellular control of obligate intracellular bacteria:
If they have the serine protease they survive the neutrophils. they overcome this defense very efficiently. If we take them out of the cells we get degradation of everything. When the inclusion burst the proteases are released. They leave off the receptors which smells the bacteria. This is how they can overcome the innate immune response.
Chlamydia, on release from the host epithelial cells, encounters neutrophils, the first line of immune defence. The neutrophils come into contact with the secreted effector protease CPAF of Chlamydia. The FPR2 present on the surface of neutrophils is targeted by CPAF. This dampens G-protein coupled receptor signalling, further preventing the downstream activation of neutrophils and enabling pathogen survival.
d. Intracellular niche
They have to adapt to the metabolism of the cell and have to protect themselves because the cell can kill this intracellular form. They live in vacuoles called inclusion bodies.
- Explain the typical courses of Coxiella burnetti infections. In which cellular compartment does the pathogen replicate?
- Which bacteria cause Rocky Mountain Spotted fever? Explain shortly the life cycle of the bacteria and how humans are infected.
Rickettsia rickettsia
Life cycle:
- R. rickettsii is maintained in infected ticks by transovarial and transstadial transmission; it can also become established in new lines of ticks by infectious feeding. Eggs from a female tick infected with R. rickettsii develop into infected larvae, which then feed on and infect small rodents with the rickettsiae that are present in their saliva. Uninfected larvae that have developed from uninfected eggs may feed concurrently on an infected animal, and depending on the magnitude and duration of the rickettsemia of the infected host, the uninfected larvae may ingest sufficient R. rickettsii in the blood meal to become infected.
Mammals including humans can be infected in different ways: bite from infected tick.
b. eating food contaminated with infected mammals feaces.
c. infected persons faeces gets into contact with open wound of an uninfected person.
- Which bacteria cause epidemic typhus? Explain the route of infection and the mechanism underlying the spreading of these bacteria in the tissue.
Rickettsia prowazekii
Route of infection:
Epidemic typhus is spread to people through contact with infected body lice.
They have a strange capacity to escape the phagosome. They can use actin to move from cell to the other cell. And then the bacteria can cause this damage in the epithelium. They do it following these steps:
- Rickettsiae enter host via skin or muscosa
- Invade endothelial cells
- Escape phagosome with the help of hemolysin and phospholipase
- Spread from cell to cell or by rupture of the cell
- Cells damage causes disruption of tight junctions vascular permeability
- Which of the features of Coxiella justify the classification as bioweapon category B?
Because of the aerosol transmission, a low infectious does, and the debilitating nature of acute Q fever.
- In which cell type replicates Anaplasma phagocytophilum? Which features of these host cells are relevant for obligate intracellular bacteria?
They replicate inside mammalian white blood cells and tick salivary-gland and midgut cells.
The subvert the host by no synthesizing LPS and peptidoglycan. They employ the host cholesterol to stabilize the membrane. Anaplasma uses the autophagic pathway to generate niche for replication in Granulocytes. Anaplasma interferes with apoptosis signaling.
- How does Anaplasma modify its host cell to efficiently replicate?
They interfere with immune response and apoptosis.
. In which cell type replicates Ehrlichia chaffeensis? Do you know other pathogenic bacteria, which replicate in the same cell type? How do these bacteria modify these host cells, to be able to efficiently replicate?
Replicate inside monocytes and macrophages. They replicate in the same cells as Coxiella burnetti.
