Salmonella

• Describe salmonella, the organism

  • Gram negative, motile, facultative, rod-shaped anaerobe
  • Member of enterobacteriaceae
  • 2 species
  • Infect a broad range of hosts, including humans
  • Estimated 1.35 million infections and 420 deaths
  • Food is the main source of infecion
• Describe S. thyphimurium infections

  • major cause of gastroenteritis in the developed world
  • consumption of contaminated food is major source of infection
  • contact with reptiles and amphibians can also lead to infection
  • colonisation of farm animals makes it difficult to eradicate from the food chain
• Describe the difference in infection outcomes with S. typhimurium and typhi

  Typhimurium-

  • infection is localised with a short incubation period (12-72h)
  • causes nausea, vomiting And diarrhoea
  • characterised by vigorous inflammatory response and severe neutrophil infiltration

  Typhi

  • infection disseminated and longer incubation period (10-14 days)
  • non-specific flu-like symptoms
  • limited neutrophil influx
• Describe interaction of salmonella with the host

  Salmonella will preferentially enter M cells, which are specialised cells associated with mucosal lymphoid tissue that are able to transcytose luminal antigens including microbes. Salmonella is therefore presented to the underlying lymphoid cells in the Peyer’s patch.
• Describe the key salmonella virulence determinants

  Fimbriae-

  • Variety of fimbrial adhesins, e.g., type I Fimbriae (fim genes) and plasmid encoded fimbriae (per genes)
  • Fim binds to M cells

  Pathogenicity islands

  • SPII and SPI2- encode T3SS for infection of effector proteins
  • SpI7 present in Typhi causes inflammatory diarrhoea and encodes the Vi capsular antigen
• Describe salmonella cell invasion

  1. Salmonella bind to host cell microvilli
  2. Salmonella stimulates membrane ruffling and enter via endocytosis.
  3. Bacteria remain inside vesicle referred to as salmonella containing vesicle (SCV)
  4. Bacteria multiple inside vesicle and cell surface remains normal, allowing bacteria to evade the immune system.
• Describe salmonella pathogenicity island- SPII

  • SPII encodes a type III secretion system involved in initial interaction with host cells
  • delivers effector proteins into host cell cytosol
  • actin cytoskeleton rearrangement
  • membrane ruffling
  • salmonella invasion
• Describe the interaction between T3SS effector proteins and host cells

  SipA and SipC effector proteins interact directly with actin, causing nucleation and polymerisation. SopE and SopE2 effectors proteins act as GEFs to activate host cells Rho GTPases, leading to actin remodelling and cytoskeleton changes. SopB has a similar effect in activating Rho family GTPases but more indirectly. SptP is a GAP that inactivates Rho GTPase resulting in cytoskeleton recovery and reverses membrane ruffling. SptP is more resistant to host proteasome degradation so persists longer than SopE.
• Describe the action of SopB

  This is an T3SS effector protein which is an inositol phosphatase and produces PIP3 decorated vesicles that, on fusing with the SCV, create a spacious vacuole for salmonella to replicate. Also blocks maturation of endosomes and lysosomes and their fusion with the SCV, which protects salmonella from lysosome mediated degradation.
• Describe the salmonella pathogenicity island- SPI2

  • encodes T3SS involved in the later stages of interactions with host cells, including SifA, which is required for production of salmonella induced filaments (SIFS) that project from the SCV
  • delivers effector proteins into host cell cytosol from within the SCV
  • some effector proteins are encoded on SPI2, whilst others are elsewhere on the chromosme
• Describe the Vi antigen

  This is expressed during human infection and can be used within vaccines to protect against infection. This antigen cannot be expressed within areas of high osmolarity such as the intestinal lumen. It acts to downregulate TLR mediated host immune responses, which reduces IL-8 production. Vi antigen capsule inhibits the action of phagocytes and confers serum resistance.
• Describe how salmonella inhibitors TLR4 mediated recognition

  The presence of the Vi antigen on the cells urface prevents the recognition of LPS by TLR4.

  1. Enzymes encoded by the genes tviB/C/D/E catalyse conversion of UDP into a polymer
  2. This polymer is variably O-acetylated at the C3 position before being transported cross the cytoplasmic membrane, which is mediated by VexB/C/D/A.
  3. The VexE protein then attaches the Vi antigen to the cell surface.