Describe what is meant by the term invasion
after successful adhesion
involving dissemination of a pathogen throughout local tissues or the body
-> potential production of exoenzymes or toxins to allow colonisation and damage host tissue as they spread deeper into the body
-> virulence factor production against immune system defenses
=> specific virulence factors determine degree of tissue damage
Understand the benefits for bacterial pathogens living inside host cells
shielded from humoral antibodies
only elimination by cellular immune response
exploit host cell nutrients
=> enter and reproduce in “peace”
Describe the difference between facultative vs. obligate intracellular pathogens and provide some examples
obligate intracellular pathogens
facultative intracellular pathogens
can only reproduce inside of host cells
can reproduce either inside or outside of host cells
Chlamydia spp.
Legionelle pneumophila
Mycobacterium leprae
Mycobacterium tuberculosis
Coxielle burnetti
Listeria monocytogenes
Describe the 2 method employed by pathogens to invade host cells
effector proteins secretion
-> effector proteins trigger entry into host cell
surface proteins expressed
-> bind to receptors on host cell and enter through this
Briefly describe the processes of ‘trigger’ and ‘zipper’ mediated entry
trigger
insert secreted effectors into host cell after attaching to host cell
interaction of effectors with regulator targets for host cell actin dynamics -> membrane ruffling beneath invading bacteria
bacterial engulfment, internalisation into membrane-bound vacuole through macropinocytosis-like process
zipper
binding of the bacterial surface proteins to receptors on host cell membrane -> activating signaling cascade to control actin cytoskeleton
progressive entrapping of bacteria through actin-driven pseudopods
progressive bacterial engulfment until formation of phagosome
Explain the process of membrane ruffling using Salmonella as an example
triggering invasion of host cells by T3SS translocating effectors -> rearrangement of actin cytoskeleton
actin-based extension pushing against host cell membrane and enclosure of bacterium through induced ruffling of membrane
full engulfment of bacterium into vacuole -> collpase of ruffles
Understand how Y. pseudotuberculosis invades host cells
binding ot host receptors via adhesin
downstream signaling events induction leading to culmination in invagination of host membrane + extension of actin filaments around the bacterium
fusion of membrane with now enclosed bacterium in a vacuole
collapse of actin -> restoring host surface
Describe the general principles employed by bacteria to avoid intracellular (lysosome) killing
subverting endosomal trafficking and remodelling of phagosome into a hospitable vacuole
-> enhanced protection against immune recognition as key role
promoting phagosomal membrane disruption and escaping to cytosol
Describe how bacterial pathogens (and give examples of specific species) subvert phagocytosis via living within the phagosome and via phagosome lysis
within phagosome
via phagosome lysis
prevent fusion of phagosome with lysosome by secretion of effector proteins into cytosol (SPI-2 encoded T3SS-2)
lyse of phagosome before fusion with lysosome
-> insertion of T3SS into membrane and secretion of virulence factors triggering apoptosis, cytoskeleton rearrangement, etc. -> creation of own tetramer complex w. membrane and ion channels
Mycobacterium tuberculosis,
Legionella pneumophila,
Salmonella species
L. monocytogenes,
Shigella
Describe the process of cell-to-cell spread used by Listeria
in general
utilisation of host cell actin cytoskeleton to move in cytosol of infected cells and project into adjacent cells through formation of membrane protrusions
Listeria
zipper mechanism to invade host cells
escaping phagosome before fusion with lysosome
replicating in cell cytosol
spreading by acting polymerisation
promotion of cell-to-cell spreading of Listeria
rupture of two-membrane vacuole mediated by action of LLo and PC-PLC
Understand why obligate intracellular pathogens need host cells to survive and the difficulties in working with them
unable to carry out energy metabolism and lack of many biosynthetic pathways
-> depending on supply of ATP and other intermediate molecules from host cell
=> require viable eukaryotic host cells not artifical media for growth in lab
Describe the obligate pathogen Chlamydia’s life cycle
transformation between distinct forms
elementary body (EB)
reticulate body (RB)
attachment of highly infectious EB to epithelial cells -> inducing ingestion by host cell
preventing fusion of phagosome with host lysosome -> ensures EB survival
reorganisation of EB into metabolically active RB
persistent state by several stimuli incl. antibiotics and cytokines
avoiding persistence or reactivation of infection from persistence by reorganisation of RB into EB
release from host cell to infect surrounding epithelial cells
Understand the processes by which Coxiella and Rickettsiales survive inside host cells
inhalation
invasion and replication within alveolar macrophages without alerting innate immunse system -> stealth pathogen
replication within compartment similar to phagolysosome, the CCV
Rickettsiales
group of obligate intracellular vectore-borne Gram-negative bacteria w.different methods of intracellular survival
phagosome lysis involved before replication
replication in cytoplasm/perinuclear colony/membrane-bound vacuole
reticulate cells w. exocytosis and host cell lysis after replication
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