Nature reviewsMicrobiologyJanuary 2008

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

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

FlagellumT3SS

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

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

Tight junctions destabilization

Transepithelial migration

Intestinal inflammatory responses

Normal structure regainment

SPI 1 T3SS

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)

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

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

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!