salmonella Flashcards

1
Q

salmonella: the organism

A
  • gram-negative, flagellated, facultative anaerobe, rod-shaped
  • member of the enterobacteriaceae
  • differentiated serologically by:
    -> O - LPS
    -> H - flagella
    -> Vi - capsule antigens
  • over 2000 serovars each previously considered a separate species
  • reclassified intro 2 species: salmonella enterica and salmonella bongori
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1
Q

salmonella infection

A
  • infect a broad range of hosts: humans, mammals, birds, reptiles and insects
  • estimates from the CDC anually in the USA salmonella causes:
    • 1.35 million infectiond
    • 26,500 hospitalisations.
    • 420 deaths
  • food is the source of infection for most cases
  • focus on 2 serovars:
    • S.enterica serovar typhimurium
    • S.enterica serovar typhi
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2
Q

S.enterica serovar typhimurium

A

can cause:
- gastroenteritis in humans, lethal diarrhoea in calves
- systemic disease in genetically susceptible mice

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3
Q

S.enterica serovar typhi

A

can cause:
- systemic infection in humans only

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4
Q

S.typhimurium infections

A
  • major cause of gastroenteritis in the developed world
  • consumption of contaminated food is major source of infections
  • contact with reptiles and amphibians can also lead to infection
  • colonisation of farm animals generally asymptomatic - difficult to identify contaminated animals and eradicate form food chain
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5
Q

salmonella typhi infections

A
  • the typhi is very rare in this country or Higher income countries.
  • over the first part of the last century the numberof cases decreased rapidly and that’s largely due to sanitation gain

the percentage of cases that are attributed to travel have risen.
- So they’re almost all typhi cases in the America and likely other as comparable High income countries are due to imported cases.
- So where people travel to parts of the world where rates of infection are much higher and then import those infections.
- So largely typhi has been dealt with in higher income countries.

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6
Q

slamonella typhi cases

A

So Salmonella Typhi is a global pathogen.
Is still highly significant.

  • estimated 20 million typhoid cases annually with 200,000 deaths
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7
Q

infection outcomes with typhmurium

A

gastroenteritis

  • infection localised
  • short incubation period (12-72 hours)
  • nausea, vomiting, abdominal pain, diarrhoea, fever
  • characterised by a vigorous inflammatory response with sever neutrophil infection
  • infection lasts under 10 days
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8
Q

infection outcomes with typhi

A

typhoid fever
- infection disseminated - intestine to liver, spleen and bone marrow
- longer 10-14 day incubation period
- non specific flu-like symptoms
- limited neutrophil influx, infiltrate mainly mononuclear cells (macrophages and dendritic cells)
- infection lasts 4 weeks if untreated and can lead to carrier state within bile duct with excretion in urine/ faeces for years

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9
Q

typhoid carrier - Mary

A
  • asymptomatic carrier of S.typhi but worked as a cook
  • refused to recognise that she was cause of typhoid outbreaks and was forcibly quarantined
  • released in 1910 and continues to work as a cook causing more outbreaks and deaths
  • quarantined in 1915 and died in quarantine of pneumoniae age 69 in 1938
  • S.typhi found in gall bladder at autopsy
  • in total caused 47 infections and 3 deaths
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10
Q

what happens when salmonella enterica serovars Typhimurium and typhi interact with the host

A

the intestinal epithelial cells that line the gut are the first cells that the bacteria will come into contact with
And then we have a different type of cell in the gut called M cells or microfold cells and they are evolved to capture content from the Lumen and present them to the innate immune system
- so when salmonella interacts with these M cells, it’s taken up By those cells into a vacuole and then it interacts and is presented to cells of The Host Innate immune system
- So of they’re able to trancytose across this barrier and emerge beneath the epithelial cells here. Then they will come into contact with all of these types of cells that have been recruited by the sensing innate immune system.

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11
Q

M cells

A

specialised epithelial cells associated with mucosal lymphoid tissue that can transcytose luminal antigens including microbes that can then be presented to phagocytic immune cells

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12
Q

polymorphonuclear leukocyte (PMN)

A

a type of granulated white blood cells including neutrophils, eosinophils and basophils

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13
Q

differing outcomes when salmonella enterica serovars Typhimurium and typhi interact with the host

A

gastroenteritis - non typhoidal salmonella serovars induce a more localised inflammatory response in which PMNs are recruited and enter the gut lumen resulting in diarrhoea

enteric fever- typhoidal salmonella serovars are disseminated by intestinal macrophages through the reticuloendothelial system onto the lymph nodes, liver and spleen.
- can survive in the macrophages and hide in them

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14
Q

how does salmonella enterica serovar typhi persist within hosts

A

We get ingestion through M cells, presentation to a macrophage, taken up into your macrophage within a vacuole and then survival within this vacuole.
- Now most bacteria that are taken up into a macrophage will be destroyed because it’s incredibly hostile environment.
- salmonella is able to avoid this outcome.

Within These macrophages and through the lymph they can travel to the mesenteric lymph nodes onto the spleen and the bone marrow onto the liver and into the gallbladder.

So this formation of a carrier State once the initial round of symptoms of resolved then patients will become asymptomatic and will think the infection has been cleared but it hasn’t and from the gallbladder it’s relatively straightforward to reseed the Lumen through the bile, therefore Releasing more salmonella typhi into the environment through the feces

So the carrier State leads to recurrence release of salmonella typhi into the environment.

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15
Q

key salmonella virulence determinants - fimbriae

A

variety of fimbrial adhesins:
-> type 1 fimbriae (fm genes)
-> plasmid-encoded fimbriae (pef genes)
-> long polar fimbriae
-> thin aggregate fimbriae

S.Typhimurium genome has 13 fimbrial operons
- only fm and pef expressed in vitro
- further nine expressed in vivo (in mice) - in vivo signal

16
Q

key salmonella virulence determinants - salmonella pathogenicity islands

A
  • SP11-12 - more or less well characterised
  • SP11 and SP12 encode T3SSSs for injection of effector proteins
  • SP17 present in typhi but not in salmonella that causes inflammatory diarrhoea
17
Q

salmonella cell invasion

A
  • host cell microvilli
  • membrane ruffling
  • bacteria remain inside vesicle referred to as SCV (salmonella containing vacuole
  • bacteria multiply inside vesicle, cell surface returns to normal
18
Q

salmonella pathogenicity islands - SP11

A
  • SP11 encodes a type 3 secretion system involved in initial interaction with host cells
  • delivers effector proteins to host cell cytosol:
    -> actin cytoskeletal rearrangements
    -> membrane ruffling
    -> salmonella invasion
19
Q

interaction of salmonella with epithelial cells

A

both SipA and SipC effector proteins interact directly with actin, causing nucleation and polymerisation
SopE and SopE2 effector proteins act as guanine nucleotide exchange factors, to activate host cell RhoGTPases Cdc42 and Rac, again leading to actin remodelling and cytoskeletal changes
sopB has a similar effect in activating Rho family GTPases but more indirectly likely through a host-encoded GEF

20
Q

interaction of salmonella with epithelial cells - SopB

A

is an inositol phosphatase producing phosphatidyl inositol 3 phosphate decorated vesicles that on fusing with the SCV create a spacious vacuole for salmonella to replicate

21
Q

interaction of salmonella with epithelial cells - SptP

A

a GTPase-activating protein that inactivates the Rho GTPase switch results in the cytoskeleton’s recovery and the membrane ruffling’s disappearance.
SptP is more resistant to host proteosome degradation than Sop E so persists and reverses the StopE mediated cytoskeletal changes

22
Q

interaction of salmonella with epithelial cells - subversion of endocytic pathway

A

SopB phosphoinositide phosphatase activity also blocks maturation of endosomes/ lysosomes and their fusion with the SCV, protecting salmonella from lysosome - mediated destruction

23
Q

salmonella pathogenicity island - SP12

A
  • 40 kb pathogenicity island identified in 1996
  • SP-12 encodes a type 3 secretion system involved in later stages of interaction with host cell
  • delivers effector proteins into host cell cytosol from within SCV
  • some effector proteins are encoded on SP1-2, others elsewhere o the chromosome
24
Q

properties of the Vi antigen

A
  • expressed during human infection
  • vaccination with Vi antigen is protective
  • SPI 7 is genetically unstable and can be lost with frequent in vitro passage
  • loss of Vi antigen results in 10,000 fold reduction in virulence
  • not expressed under conditions of high osmolarity such as the intestinal lumen
  • Vi antigen down regulates nthe TLR- mediated host immune response - reduces IL-8 production
  • Vi capsule inhibits phagocytosis and confers serum resistance
  • salmonella typhi is a stealthy pathogen
25
Q
A