L10 - Bacterial Survival Mechanisms Flashcards
What are the main mutualistic and pathogenic associations with protein secretion
Secreted protein enters host cells and modifies host physiology
Necessary for bacterial survival by promoting colonisation of hosts (toxins and effector proteins)
How is the exporting of proteins achieved by bacteria?
Secretion systems
What are the 2 types of secretion systems? Which is more common
Sec (general secretion) - most common way
TAT (Twin arginine translocation) - only in bacteria and transports fewer substrates than sec
What does sec require?
Signal peptide or leader sequence
Describe how Sec works
System that moves the protein using translocase
- bacterial proteins are described in 3 letters and then a group of proteins ina. group (ABCD)→ so SecA, B, C are all Sec proteins
- sec proteins is called translocase unit that makes a channel from where the protein is moving
- inside the membrane we have ATPase which is where teh system gets its energy to make all the conformational changes to move proteins out
- main characteristic = moving proteins in a non-linear way, unfolded proteins
- sequence recognised by chaperone and delivered to target area
Describe how TAT works
Tat → controls the chaperone and obtains energy from proton motive force, has 2 arginine
- two arginine are part of the signal sequence that tell bacteria that these proteins are going specific ways (green)
- this system allows the proteins to be moved in a 3D folded way (folded proteins are translocated)
- protein in charge to get close to chaperone and uptake energy from the proton motive force
Describe the secretion systems in listeria (gram positive bacteria)
- phage take up macrophage and enters vacuole
- bacteria needs to produce diff proteins for this process
- e.g. bacteria needs to break the vacuole using diff proteins
- these proteins are outside cell membrane
- toxins needs to be released into surrounding area
- intercellular pathology is translocated to peptidoglycan using Sec translocation system
- there are also anchoring proteins (not important)
How are proteins transported in gram negative bacteria? What systems help transport through inner vs outer?
Inner = TAt and Sec
Outer = type 2 Type 5, type 8 type 9
Describe the type 2 secretion system T2SS
- sec dependent
- importance in cell physiology and virulence
- role in pilus biogenesis
- ribosome goes through sec system
How is T2SS used in vibrio cholera
Cholera toxin is already within the periplasm and T2SS releases it out the cell through the membrane
How does cholera toxin lead to diarrhoea?
Cholera toxin binds to GM1 ganglioside receptor. It is endocytosed and trafficked to ER. Activates adenyl cyclase system and increases cAMP levels. Triggers inhibition of reabsorption of Na+ and K+ ions and hypersecretion of Cl-
Osmotic gradient so water moves into teh intestinal lumen
In gram negative bacteria, T1SS is used to pump directly out. How does it work
- Double membrane spanning export system
- translocate across 2 membranes in one step
- energy of ATP is converted
- transmembrane protein acts as bridge
- OMP = tube
Why is gram negative better at reaching host when transporting virulence factors?
- gram -ve has the capacity to not only transport but also reach a host membrane
- much more clever bc type 1/2 is released into the environment (dilution factor)
- if you put your protein direclty into the target host cells it is much more effective
- you are sure you always have energy so you dont need several systems to gain energy (3,4,6)
Which secretion systems injects directly into host membrane?
T3SS, T4SS, T6SS
Describe how the T3SS works?
- syringe shaped injectisome
- delivers effector protein across bacterial and host membranes into cytosol of host
Describe the structure of the injectisome in T3SS
Translocation = moves into cytosol of host cell, tip complex at the distal end
Needle complex = membrane anchored base protruding needle filament
Basal body == inner membrane proteins
Cytoplasmic sorting platform = selects and delivers the substrates to be exported
What proteins and effector target cell signaling is achieved through T3SS?
- cytoskeleton
- T-junctions barrier function
- cell cycle
- inflammatory responses
- mitochondrial function
- apoptosis
How is the T3SS gene expression regulated?
Contains 20 proteins that are tightly regulated. Encoded in the same gene so only secretes when they sense they need it
Give an example of bacterium that uses T3SS to interact w host cell
Salmonella typhimurium
Outline the 2 diff gene clusters that forms T3SS in salmonella typhimurium
T3SS-1 - early invasion and activation of proinflammatory responses
T3SS-2 - later phase of infection, intracelllar survival and replication within macrophages
What are the 4 secretion systems in salmonella
1,3,4,6
Out of T1SS, 3, 4, 6 which ones can trans pass 3 membranes
3,4,6
What is T4SS
- DNA and protein transfer
- in both gram bacterias
How is T4SS different to T3SS
Present in both animal and bacterial cells
