Download - Nature reviews Microbiology January 2008
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Nature reviewsMicrobiologyJanuary 2008
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Gram-negativeEnterobacteriaDiameter 0.7 - 1.5 µmS. enterica serovar Typhimurium serovar Typhi
Daniel Elmer Salmon Theobald Smith
WHO: typhoid fever16 million cases of per year600 000 fatal cases
Ways of acquirement:- Contaminated food and water- Exposure to reptiles and amphibians
Salmonella sp.
Diseases range from mild diarrhoea to severe typhoid fever
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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
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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
FlagellumT3SS
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9 KDa T3S proteins
100-150 subunits
Length: 60-80 nm
Width: 8 nm
Inner diameter: 3 nm
Needle complex (NC)
Proteins – effectors:
N-terminal secretion signal
Binding site for chaperone
Chaperones can act as transcription factors
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Two distinct T3SSs are encoded within Salmonella pathogenecity islands (SPI)
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Salmonella SPI1 encoded type III secretion system and it’s effectors
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SPI 1 T3SS
Activation of the Rho GTPases
Actin cytoskeleton rearrangement
Bacterial-mediated endocytosis
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Salmonella SPI1 encoded type III secretion system and it’s effectors
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Tight junctions destabilization
Transepithelial migration
Intestinal inflammatory responses
Normal structure regainment
SPI 1 T3SS
Salmonellae might be evolving towards parasitism or commensalism
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Effectors of the Salmonella SPI2 encoded type III secretion system
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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
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Effectors of the Salmonella SPI2 encoded type III secretion system
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Formation of the Salmonella induced filaments (Sifs)
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
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
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Sensing and response to the vacuole
LPS
Antimicrobial peptides:PhoQ sensor and surface remodellingDecreasing length of the O antigenAlterations in lipid A
Oxygen and nitrogen radicals:Cu,Zn superoxid dismutases
919 genes in S. typhimurium are upregulated in phagosome
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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
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