What are the benefits for pathogens to go into host cells
They can avoid extracellular immune system, so a little safer
They can access nutrients and machinery of the host cell
They can manipulate the host cell, hijack its signalling pathways, metabolism, membrane trafficking, etc, to its advantage
Specific to virus: used to replicate itself
Steps in phagocytosis by a neutrophil
Chemotaxis: the pathogens releases signals or something recognizable to neutrophils that result in the WBC being drawn to it, it diffuses in a gradient so it can track it that way
Actin-driven engulfment: the cell binds to the receptor of the pathogen, this causes actin remodelling making it capable of wrapping around the pathogen
Phagosome formation: post-engulfment, phagosome is formed, eventually matures into a phagolysosome for digestion
Zipper mechanism of bacterial entry
Bacterial cells produce a lot of cell surface receptors, invasin receptors, recognizable by the target cell, the host cell recognized them, binds them, and this binding triggers signalling pathways like Arp2/3 and WASp proteins that will result in actin remodelling to accommodate the incoming bacterial cell, the signalling pathway was triggered by Rho GTPase family, CCV forms, bacterium enters
Note that different pathogens will bind different host cell receptors, like integrins or cadherins or others
Trigger mechanism of bacterial entry
The bacterial cell does not produce cell surface receptors, instead it uses the T3SS system once in proximity to the cell, the T3SS injects effector proteins
Some effector proteins trigger the same Rho GTPases and signalling pathways as the zipper mechanism, but others may bypass the GTPase and act directly on the actin polymerization proteins
From then on its the same idea as before, the actin wraps around, engulfs the bacterium, its inside
What routes can the pathogen go down to to survive once inside cell
Once inside its a phagosome, and its destiny is to fuse with the destructive lysosome, cant have that, so it can
Escape the phagosome, quite literally break free and run off
Modify the phagosome such as to change its fate and not have it fuse with lysosome
Can weather the storm, survive within the phagolysosome if its adapted to do that
Listeria escaping the phagosome
Bacteria that escapes by breaking free of the phagosome, as the pH of the phagosome drops, the bacterium secretes listeriolysin, this protein can act on the membrane and break it down, this breaks the compartment such that the listeria bacteria can run off into cytosol directly
Note: once in cytosol the listeria bacteria is still producing listeriolysin, but because were at a neutral pH its not affecting other membranes
Bacterial pathogen motility once inside host cell
Some bacteria just chill as they reproduce, but others want to move around so they have a mechanism where they cause actin polymerization on one end of the bacterium such that it forms a make-shift flagellum for motility
These bacterial cells then drive themselves into the host cell membrane, sometimes even making channels between cells (fusion almost) or just being endocytosed into neighbouring cells to proliferate elsewhere, they do this by driving themselves into the membrane and making a protrusion that is then phagocytosed
How did listeria build its make-shift flagellum
It produced ActA, on one end, which basically could activate Arp2/3 and initiate actin polymerization on said end
Note: gram +ve bacteria
How does shigella build its make-shift flagellum
It produces IcsA from its virulent plasmid, a surface protein, that recruits the cells own WASp proteins and then Arp2/3 complex, so like an extra step but the same result
Note: Gram -ve
How does rickettsia bacterium produce its make-shift flagellum
It expresses a surface protein, formin like protein, and its directly capable of nucleating actin, it polymerizes actin without arp2/3 intervention
Often found in mammalian cells (slide 11)
What do mycobacterium do in phagosome do to prevent its fusion with a lysosome
Mycobacterium keeps it in a state that’s similar to early endosome, basically keeping the same cell surface markers so that it doesn’t progress into endocytic pathway, just giving off vibes of maturing, still communicates with PM
What do salmonella do in phagosome do to prevent its fusion with a lysosome
Salmonella keeps it in the late endosome state, does not communicate with PM
How does legionella do in phagosome do to prevent its fusion with a lysosome
It wraps itself in a kind of ER like membrane, studded with ribosomes and communicates with PM via vesicles this way
Acts like TGN
SCV
Salmonella containing vacuole
Basically for salmonella to get inside the host cell, it uses its pathogenicity island, SPI1, which has a T3SS used for insertion via the trigger mechanism, but once inside it inactivates it and activates the SPI2, one with T3SS ability to release special effector proteins to remodel/transform the phagosome into a specialized vacuole, an SCV
Once the SCV is established, theres no more risk of it fusing with a lysosome, and it can also manipulate the hosts kinesins to form/rearrange microtubule structures to better serve the SCV
Legionella bacteria and how it survives in host cell
Enters via phagocytosis, once inside it uses a T4SS to secrete effectors, very diverse, and these effector modulate the proteins typically involved in vesicular trafficking, such as SNAREs, Rab, Arf and other GTPases, these effectors prevent the phagosome from fusing with the lysosome but rather with transport vesicles, turning into a pseudo ER that is eventually studded in ribosomes
How can viruses be classed
Can be class according to size, according to membranes/envelopes , according to DNA or RNA
In a nutshell whats a virus
A virus is basically genetic information, either RNA or DNA, and a protective layer (capsid), could have an envelope
The genetic info can pertain to one of three things: proteins for replicating the genome, proteins for packaging and delivering genome into host, proteins for modifying/manipulating the structure of the host cell for its benefit
DNA vs RNA virus and replication
DNA viruses cannot replicate until its information has entered the nucleus, this because the relevant transcription material is in there, pox virus is an exception that can technically duplicate its genome without a host
RNA viruses do their replicating in the cytoplasm since their genome is already in RNA form, can skip the nucleus step, like retroviruses like HIV that reverse transcribe their RNA into DNA and insert it into the host genome
Positive vs negative sense RNA viruses
Positive sense viruses already contain their mRNA ready from their RNA genome, like that RNA is the same as the mRNA
Negative sense viruses have to make their positive sense RNA before they can produce, meaning their genome is the complimentary strand of the mRNA, so it has to be copied before it can be translated
Hepatitis B genome
Special genome, it has partially double stranded DNA, like it sounds some parts are ds and others single, so for all intents and purposes it acts like an RNA virus in that it has to make a positive sense strand first
Viral replication
Virus starts off with a coat, enters the target cell, sheds the coat to expose the genetic info (DNA or RNA), it’ll eventually get transcribed and replicated (like making copies of the genome) and further translation with produce more coat proteins that will package up this genomic info into many more viruses, they will eventually leave the cell to go proliferate even more
Bacteriophage
Has a head, tail fibres, core, similar to virus except specific to infecting bacteria, the helical domain is like a syringe that will inject DNA
Tail fibres feel out the cell surface and bind if theres a surface receptor for it, if there is then the other fibres will “land”, 6 total, strengthening the interaction, and thats when the syringe structure punctures the cell and injects its genome
A type of virus
Do bacteriophages enter bacterial cells
No, its easier to just inject the genomic info because of how thick and numerous the cell layers/membranes are
HIV and mammalian cells
HIV viruses have a gp120 protein that binds to CD4 on helper T cells and macrophages, and once bound it causes a change in conformation and calls another protine, beta-chemokine, they interact, and this results in a much stronger interaction for the virus to enter the cell
Note: it can also progress to bind other co-receptors such as CCR5 and CXCR4, this is variant dependent
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Light Microscopy 131
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Light Microscopy 237
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Light Microscopy 331
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Electron Microscopy 132
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Electron Microscopy 230
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Stochaj 141
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Stochaj 226
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Stochaj 334
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Cytoskeleton 120
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Cytoskeleton 229
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Cytoskeleton 336
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Cytoskeleton 429
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Membrane Trafficking 122
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Membrane Trafficking 213
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Membrane Trafficking 310
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Membrane Trafficking 419
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Endocytosis 123
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Endocytosis 219
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Endocytosis 335
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Endocytosis 416
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Lipid Droplets 132
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Pathogens 125
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Pathogens 239
