Lecture 12 - Intra-vacuolar Survival Flashcards
How does phagosomal maturation occur?
1)
2)
1) Early, late endosomes and lysosomes in the cytoplasm
2) These kiss and run phagosomes, depending on which surface markers the phagosomes are displaying, and help mature phagosome
Surface marker of late phagosome
LAMP-1
How do phagosomal surface markers select specific endosomes?
Surface markers are SNARE proteins, EG: EEA1 (early endosome antigen 1)
V-ATPase
Vacuolar ATPase
Present in membrane of late phagosome
H+ pump, decreases pH in late phagosome
Which stage of vacuolar development does Mycobacterium live in?
Early endosome
Which stage of vacuolar development does Salmonella live in?
Late endosome
Which bacterium halts phagosomal development at early phagosome?
Mycobacterium
Which bacterium halts phagosomal development at late endosome?
Salmonella
Which bacterium lives in late phagosome?
Coxiella
What does Coxiella burnetii cause?
Q fever
Causative agent of Q fever
Coxiella burnetii
Surface markers for late endosome
LAMP1, LAMP2, cathepsin D
What is cathepsin D?
A protease
Environment that Coxiella burnetii needs to replicate
Acidic
Below pH 5
Close relative of Legionella
Coxiella burnetii
Close relative of Coxiella
Legionella
Secretion system used by Coxiella and Legionella
Type IV secretion system (Dot/Igm)
Endosome always associated with macropinocytosis
Recycling endosome
Filament produced by Salmonella in a vacuole
Salmonella induced filament (Sif)
Where is Salmonella induced filament expressed?
Salmonella containing vacuole
Phagosomal components missing in SCV
1)
2)
3)
1) Cation-independent mannose-6-phosphate receptor
2) Lysosomal enzymes
3) NADPH oxidase in phagosomal wall
Which bacterium resides in a spacious phagosome?
Salmonella
Which bacterium expresses SifA?
Salmonella
Protein expressed by Salmonella to induce Sif formation
SifA
Targets of SifA
Rab7
SKIP (mammalian kinesin binding protein)
Kinesin
Protein involved in transporting vesicles along microtubules
Movement of Salmonella-containig vesicle
From periphery down to near nucleus
What encodes SifA?
SPI-2
Which kind of pathogen is Legionella?
Facultative intracellular pathogen
Human cell in which Legionella replicates
Alveolar macrophage
How good is Legionella at avoiding human immune system?
Very poor.
Stimulates a strong immune response, normally doesn’t lead to infection. Only dangerous in the immunocompromised
Didn’t evolve to evade human immune system
At which stage does Legionella halt phagosome formation?
Doesn’t even interact with early endosome.
Very, very early
Proteins associated with Legionella-containing vesicle (LCV) 1) 2) 3) 4) 5) 6)
1) Rab1
2) Arf1
3) Sec22b
4) Calnexin
5) Sec61
Calnexin and Sec61 are ER proteins
What is Arf1?
A GTPase
Involved in vesicle trafficking
Type IV/Dot/Icm system
Pore-forming system
Delivers effector proteins through pores in host cell membrane
Number of proteins involved in Dot/Icm
Over 300
1/3 of Leigonella genome dedicated to invasion
Which bacterium expresses RomA?
Legionella
Important protein expressed by Legionella, involved in epigenetic remodelling
RomA
RomA function
1) Contains SET domain
2) SET domain is in eukaryotic histone lysine methyltransferases
3) RomA has a nuclear localisation sequence, enters the nucleus
4) Trimethylates histone H3K14, leading to transcriptional repression of TLR, cytokine genes
Unusual feature of RomA
Trimethylates H3K14, which is never methylated normally
Normally H3K14 is acetylated
Genes repressed by RomA
Cytokine, TLR genes.
