Pathogenesis Of Bacterial GI Diseases: Salmonella, E.coli and Campylobacter Flashcards
Salmonella
-has different serotypes/strains separated by surface antigens O & H (O antigen part of LPS & H antigen which is flagella protein) (>2500 serotypes)
-but only 2 main species; S.enterica and S.bongori
The combination of the different antigenic types of O & H antigen produce the different…
Serotypes of salmonella
Give an example of salmonella serotypes and what species it comes from
S.typhirium= S.enterica serotype Typhimurium
2 extremes of salmonella
Enteritis & Systemic infection salmonella
Enteritis vs systemic infection salmonella
-where is it found
-broad or specific host range serotypes?
-zoonotic?
Enteritis
-humans and animals
-broad host range serotypes
-zoonotic
Systemic infection
-humans and animals
-specific/restricted host range serotypes
-not usually zoonotic
Modern problems with salmonella
Multiple antibiotic resistance in both types of salmonella is a big problem – need for new antibiotics
Need for better vaccines
Salmonella are invasive pathogens. What does this mean
Can cross the mucosal barriers, generally in the gut
Commonest route for salmonella to get not body
Faecal-oral route, ingested in food
How do salmonella transport themselves through the mucosal barriers
-Directly cross on enterocytes (cells of intestinal gut epithelium)
-taken up by M cells
Once salmonella gets through mucosal barrier of gut, what happens
Go onto cause either enteritis or systemic infection
If enteritis:
-promotes massive influx of neutrophils
If systemic infection; promotes monocytic infiltrate and are taken up by macrophages as they can survive and replicate within them
Process of salmonella infection after entering gut through M-cell
-After entering, taken up by macrophages where they replicate and survive in them
-macrophages mobile so they take salmonella to local lymph nodes, proliferate in them
-transported to blood then swim about looking for organs with many macrophages in them
Each serotype can produce many different types of…
Fimbriae/pili
What are Fimbriae on bacteria and what’s their function
hairlike appendages, 1 to 20 microns in length and often occurring in large numbers, present on the cells of gram-negative bacteria
play an important role in adhesion of the bacteria to surfaces or to other bacteria
How does Fimbriae adhesion/attachment/ transport of proteins work?
Use of molecular syringes called Type III secretion systems (TTSS)- structure spans from cytoplasm of bacteria across its membrane to cytoplasm of other bacteria and injects these effector proteins into interior of cell
Where are genes for TTSS often located om
Pathogenicity islands (groupings of virulence factors on genome eg toxins, adhesions, invasins, secretion systems)
How many pathogenicity islands (PI) found in salmonella
What are the 2 most important ones
17
- SPI 1 & SPI 2
Different pathogenicity islands encode different…
Type III secretion systems
What function of bacteria is SPI 1 responsible for encoding?
What function of bacteria is SPI 2 responsible for encoding?
1.Invasion of epithelial cells to promote enteritis
2.Replication/survival in macrophages
Describe the process of salmonella invasion of epithelial cells leading to enteritis
-attachment of Fimbriae to enterocyte
-type III secretion system (SPI 1) attached to cell inject effector proteins
-membrane of cell changes shape & salmonella gets taken up into vacuole
-salmonella migrates within enterocyte and exits through cell into underlying tissue leaving cell unharmed
-goes on to cause enteritis
What does salmonella causing enteritis results in within gut
Massive influx of neutrophils
Massive inflammatory response
Causes Destruction of architecture of gut epithelium leading to diarrhoea
Diarrhoea is efficient for…
Transmission of salmonella
Why does salmonella want to promote an inflammatory response
Escherichia coli
-what kind of disease; found in who
-what kind of infection; found in who and causes what
-zoonotic or no
Diarrhoeal disease - Humans & animals
Extraintestinal infections – Humans & animals
-causes;
– UTI
– Neonatal septicaemia
– Mastitis
– Others
Most strains not zoonotic
Which 3 strains of E.coli are found in humans AND animals
• Enterotoxigenic E.coli (ETEC)
• Enteropathogenic E.coli (EPEC)
• Enterohaemorraghic E.coli (EHEC)
E.coli strains/pathotypes have different virulence factors. Name each ones for each strain:
-ETEC
-EPEC
-EHEC
ETEC: Heat labile enterotoxin (LT), heat stabile enterotoxin (ST), particular types of fimbriae
EPEC: Pathogenicity island (LEE) which encodes Type III secretion system, intimin, particular fimbriae
EHEC: Same as EPEC + Shiga toxins/Vero toxins (ST)/ (VT)
Enterotoxigenic E.coli (ETEC)
-invasive or no
-cause…
-found in…
-zoonotic or not
• Non-invasive
• cause Non-inflammatory, watery diarrhoea
• in Young of many animal sp., pigs, cattle, sheep etc • Travellers diarrhoea humans - different strains
• Non-zoonotic
What is the reason for ETEC not being zoonotic
Fimbriae in human strain and Fimbriae in animal strain are different; human strains Fimbriae only attaches to human cells and vice versa
What are the 2 different types of toxins produced by ETEC
Heat labile (LT) & heat stabile (ST) toxins
How does heat labile toxin work
Portion of it is enzyme NAD; gets into interior of cell where it targets a G protein inside cell. Takes an ADP-ribose group from NAD & attaches itself to the regulatory G protein and switches it on permanently—> results in very high levels of intracellular cyklin cAMP
How does heat stabile toxin work
Binds to guanilin receptor linked to enzyme guanylate cyclase which makes intracellular cyklin molecule cGMP
What is the result of heat toxins in ETEC producing cyklins in cell
Disturbances in electrolyte transport and as a consequence water absorption which leads to—>
Water balance in the gut changes from net absorption to net secretion of water; watery diarrhoea
Difference between pathogenicity of ETEC vs Salmonella
ETEC—> remains extracellular and diarrhoea is non inflammatory
Salmonella—> invade cells and diarrhoea is inflammatory
Enteropathogenic E.coli (EPEC)
-Cause what
-unique characteristic of it
-watery diarrhoea in lambs, calves, piglets, puppies and children
-has a pathogenicity island;locus of enterocyte effacement (LEE) encodes Type III secretion system
-sits on top of the enterocyte cell
Enterohaemorrhagic E. coli (EHEC)
-Causes what
-zoonotic or not
-contain…
-causes haemorrhaging colitis & Haemolytic uraemic syndrome
(HUS).
-zoonotic
-contain pathogenicity island; same as EPEC; put on this pedestal on top of enterocyte cell
How is EHEC able to cause haemorrgaic colitis & haemolytic syndrome
Possess shigo or vero toxins
What are Shiga/vero toxins
-structure
Large toxins
- A subunit (enzyme which inhibits protein synthesis by chopping off a bit of rRNA which prevents tRNA binding) ,
-B subunit (binding component, determines specificity of cells that are affected)
What is the main target of B subunit in shiga or vero toxins
endothelial cells of blood vessels
•Oedema
•Haemorrhage
•Thrombosis
Which pathotype of E.Cole is the only zoonotic one
EHEC
Where are EHEC carried in body, symptomatically or not?
Asymptomatically in intestine of certain animals
What does Haemorrhagic Colitis (HC) cause
Sudden onset of sever cramps and abdominal pain Bloody diarrhoea
Nausea and vomiting
Little or no fever.
What does Haemolytic uraemic syndrome (HUS) cause -what is it
-where does it most commonly occur
-what may make this illness worse?
Haemolytic anaemia
Thrombocytopenia
Renal failure
A condition in about 10% of patients caused by EHEC. Giving patients with this condition antibiotics will cause lysogenic bacteriophages to enter the lytic cycle and kill bacteria, however. (Lysogenic bacteria contains shiga and vero toxins) when entering a lytic cycle they will release even more shiga and vero toxins, then it will lyse producing even more shiga toxin causing even more toxicity.
Antibiotics may make worse!
-most commonly following infection in children
Campylobacter
-shape
-leading cause of. What in humans
-zoonotic or. Not
-cause what
-main source
-who can be carriers of this
-cause what in other animals
-gram +ve or -ve
-Spiral shaped bacteria with 2 flagella on either side
-Leading cause of bacterial food poisoning (enteritis) in humans
-zoonotic
-Can cause watery/bloody diarrhoea
-main source; chickens
-Many companion and domestic animals can be carriers of campylobacter
-Can cause enteritis in some animals eg dogs & cats, and some can cause abortion in sheep/cattle
-gram -ve
Campylobacter pathogenesis
Invasive pathogens; invade mucous membranes and once there stimulate inflammatory response
