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Nature reviews
Microbiology
January 2008
Salmonella sp.
Gram-negative
Enterobacteria
Diameter 0.7 - 1.5 µm
S. enterica serovar Typhimurium
serovar Typhi
Diseases range from mild
diarrhoea to severe typhoid fever
WHO: typhoid fever
16 million cases of per year
600 000 fatal cases
Ways of acquirement:
- Contaminated food and water
- Exposure to reptiles and
amphibians
Daniel Elmer Salmon
Theobald Smith
Salmonellae preferably enter microfold (M) cells in the small intestine
Severe acute necrotizing enteritis
Normal Peyer’s patches and ileum
Non typhoid strain infection is limited to intestine
Some Salmonella serotypes can cause systemic illness
Virulence-associated type III secretion system (T3SS)
- mediates the transfer of bacterial proteins into the host cell
- found only in Gram-negative, mostly in pathogenic bacteria
- evolutionary related to flagellar system
T3SS
Flagellum
Needle complex (NC)
9 KDa T3S proteins
100-150 subunits
Length: 60-80 nm
Width:
8 nm
Inner diameter: 3 nm
Proteins – effectors:
N-terminal secretion signal
Binding site for chaperone
Chaperones can act as
transcription factors
Two distinct T3SSs are encoded within Salmonella pathogenecity islands (SPI)
Salmonella SPI1 encoded type III secretion system and it’s effectors
SPI 1 T3SS
Activation of the Rho GTPases
Actin cytoskeleton
rearrangement
Bacterial-mediated endocytosis
Salmonella SPI1 encoded type III secretion system and it’s effectors
SPI 1 T3SS
Tight junctions
destabilization
Transepithelial migration
Intestinal inflammatory
responses
Normal structure
regainment
Salmonellae might be evolving towards parasitism or commensalism
Effectors of the Salmonella SPI2 encoded type III secretion system
Salmonella containing vesicles (SCV) and SPI 2 T3SS
SCV – unique
phagosome, can persist
intracellularly up to
several days
Associated with early, late
endosomal as well as
lysosomal markers
Moves to perinuclear
position, associated with
Golgi
SCV is believed to be a
niche for Salmonellae
replication
Effectors of the Salmonella SPI2 encoded type III secretion system
Formation of the Salmonella induced filaments (Sifs)
Sifs - originate from the SCV
and extend throughout the cell
Possible mechanism - vesicle
budding from SCV
Requires microtubules, kinesin,
dynein, Salmonella SifA and
PipB2 effectors
The importance of the Sif formation is currently not understood
- promotes bacterial replication via increasing the size of the SCV
- redirects nutrient-rich organellas to the SCV
Sensing and response to the vacuole
919 genes in S. typhimurium are
upregulated in phagosome
Antimicrobial peptides:
PhoQ sensor and surface remodelling
Decreasing length of the O antigen
Alterations in lipid A
Oxygen and nitrogen radicals:
Cu,Zn superoxid dismutases
LPS
Summary
Salmonellae encode two virulence-associated T3SS:
SPI 1 T3SS translocates effectors across the plasma membrane
- rearrangement of the actin cytoskeleton
- destabilization of the tight junctions
- entry into non-phagocytic cells by bacterial-mediated endocytosis
- partial blocking of the NF-kB activity
SPI 2 T3SS translocates effectors across the vacuolar membrane
- Sif formation
- SCV movement to perinuclear position
- rearrangement of the cell organells
- transport of metabolic molecules into the SCV
- promotes bacterial replication within host cell
Salmonellae can sense phagosomal environment and are able to
induce various systems to promote intracellular survival
Thank you for your attention!