Myco. tuberculosis Flashcards
Explain the infectious lifecycle of Mtb
Mtb is aerosolised, goes in the lung (alveola) and interacts with macrophages.
what is the granuloma?
It then passes through the alveolar barrier and migrates to the lymph nodes. The macrophages will recruit B and T cells. This makes a ball. There is a lot of secretion of inflammation factors.
What do the 4 antibiotics do?
Mostly inhibits cell wall fromation. One inhiibits RNa polymerase
Ethanbutol: disrupts cell wall formation (disrupts Lam formation)
MDR = multidrug resistant Tb
XDR = extensively drug-resistant.
. Resistant to at least Ryph. And Iso.
Resistant to Ryph, Iso, fluoroquinones and 1 injectable second-line drug
cell wall architecture of Mtb.
–. It contains 1 plasma membrane.
Small peptidoglycan layer. Second membrane, made of mycolic acids and glycolipids (thick).
There is porins. There is Lam (glycolipid) connected to the cell membrane.
What does 2nd membrane of Mtb do?
This layer prevents antibiotics from happening and resistants chemical damage.
Ways to study bacterial virulence (in…)
Vitro = what happens to cell
vivo = study disease
Bacetrial load
How many bacteria are alive? Shown in CFU
Most genes in bacteria are found in
Operons. makes it hard to see which protein is cause of bacterial virulence
How do we do the experiments?
Knock out what we think is a virulence gene. CFU should decrease.
Reintroduce the gene back in.
If expression comes back, it’s THIS gene that’s responsible.
If the expression DOSEN’T come back, it’s due to OTHER genes in the operon. This is called a polar effect
What are cell wall glycolipids?
virulence factors. They are LamMan and TDM
How does phaogytsis usually occur?
IgG connects with opsonized bacteria. Recognised by cell, phagocytosed, fuses with lysosomes to get killed.
What does TDM do?
TDM affects granuloma formation
It interacts with Mincle to express inflammation factors and other things so that the bacteria is not killed
It also inhibits phagosome maturation
What does LamMan do?
It inhibits apoptosis, as cell death is a really important factor for survival in Tb.
LamMan changes how phagocytosis is done as the bact. Enters through a mannose receptor. This makes it so the bacteria block calcium signalling, which blocks phagosome maturation.
Name at least two virulence factors
These virulence facots prevent fusion with lysosomes
PtpA and SapM
How does PtpA work? (2 purposes)
It prevents phagosome acidification that leads to phagosome maturation. It does this by targeting and binding the subunit H of the vacuolar ATPase pump.
It also dephosphorylates host vacuolar sorting protein VPS33B.
To work, PtpA must have its catalytic domain (to VPS) and binding domain (to subunit H).
How does SapM work?
Phosphatase (desphosphorilate PI3P), a lipid.
Is a key lipid on the membrane of the phagosome TO ALLOW FUSION TO HAPPEN.
Desphosphoriliation by SapM = no more progression of phagocytosis. Some studies show that there might be some polar effects, as COMP is not as good as WT.
Does Mtb escape from the phagosome ?
cytosol through the T7SS ESX-1 secretion system.
Pros and cons of Mtb escape?
Pros: More nutrients, escape from lysosome, host-cell death, dessimination
Cons: Inflammatory response, autophagy, cytosolic surveillance
When does Mtb want to start necrosis?
TB does stay inside, so it prevents apoptosis. But at some point it will try and escape when it has replicated enough TB must initiate necrosis to escape. Necrosis is good for bacteria to escape and infects other cells.
Does Mtb produce an endotoxin or exotoxin?
Exotoxin, C-terminal of porin - CpnT
What does the exotoxin TnT do?
Cleaves NAD+
How is Mtb protected by it’s own TnT?
Operon control of TnT as well as IFT (no NAD destruction)
