Microorganisms in the Gastrointestinal Tract in Health and Disease Flashcards
1
Q
What is commensal bacteria?
A
❖ From latin commensalis: « com » = sharing, « mensa » = table —> « those that eat at the same table » ❖ = Normal inhabitant of the human body, living in communities = « Microbiota » ❖ ~1012 bacteria per gram of colon contents ❖ Neither the host (human) or the microbe is harmed, they both derive benefits
2
Q
Where do we get our commensal microbiota?
A
- Effect of maternal exposures to environment, antisepsis, antibiotics, diet, other hosts, epigenetics
- Oral (pre-mastication of food)
- Mammary, through breastfeeding (selection)
- Cutaneous (contact with skin)
- Vaginal (passage through birth canal)
- Dental amalgam
- Bottle feeding
- Early/ extensive bathing
- Caesarean section
- Early-life antibiotics
3
Q
Examples of opportunistic bacteria
A
E coli and other enterobacteria (urinary tract infections, wound)
-Bacteroides fragilis (anaerobes)
4
Q
What factors affect the GI ecosystem?
A
- pH
- Flow rate (high at top of gut, low at bottom)
- Mucus (protective layer- inner and outer)
- Competition with other bacteria= colonisation resistance
- Presence of bile and digestive enzymes
- Intestinal microbiota
- M cells and Peyer’s patch
- Antimicrobial peptides
- Redox potential/ oxygen tension (bottom of gut= anaerobic)
5
Q
What are the pathogenic mechanisms?
A
- Adherence mechanisms (avoid being flushed through)
- Toxin production (proteins, enzymes)
- Motility (swimming action to burrow through mucus layer)
- Site of pathogenicity (stomach/ intestine= adherence, colon= penetrate gut wall)
- Resistance to bile and digestive enzymes
- Avoidance of immune mechanisms (secretory antibody IgA, capsules and lipopolysaccharides)
- Immunopathological mechanisms
6
Q
Describe Helicobacter pylori
A
- Curved/ spiral, Gram-negative, microaerophile (small amount of air needed)
- Motile= mucus layer
- Causes gastritis, and gastric and duodenal ulcers (and gastric carcinoma)
- Produces urase (urea to ammonia) to protect itself from acid= urea breath test
- Very common, well-adapted pathogen
- Present in up to 50% of western adults and 100% in developing world
- Several putative virulence factors but with no simple correlations with pathogenicity
7
Q
Describe Vibrio cholerae
A
- Gram-negative, comma-shaped bacterium- motile with polar flagellum
- Water-borne pathogen (faeces) or seafood
- Sensitive to drying out, sunlight and acid so high bacterial load needed
- Causes cholera
- Cholera toxin (CT) and toxin co-regulated pilus (organelles of adherence, projections)
- CT- bacteriophage encoded (without virus is not pathogenic)- lysogenic
- Watery diarrhoea: rice-water stools (mucus in clear solution)
- Severe dehydration
8
Q
Describe the mechanism of the cholera toxin
A
- 5 B subunits and one A unit (A1 and A2)
- A bipartite, ADP-ribosylation toxin (ribosylates proteins involved in adenyl cyclase system so ATP to cyclic AMP)
- cAMP builds up so sodium pump reversed so little sodium and chloride intake and stops absorbing water
- Crypts that normally produce mucus= water pour out more, more chloride secreted
- 5 x B subunits Bind to GM1 ganglioside in enterocytes
- A subunit is Active part
9
Q
What are the types of Shigella?
A
-S. dysenteriae
-S. boydii
-S. flexneri
-S. sonnei
Members of Enterobacteriaceae
Lactose-negative, non-motile, facultatively anaerobic, gram-negative rods, low infectious load
Bacteria dysentery
10
Q
What is bacterial dysentery?
A
- Bloody diarrhoea
- Invasion of mucosa by shigellae
- S. dysenteriae causes most severe disease- only one to produce shiga toxin
- S. sonnei least severe disease
11
Q
Describe the pathogenesis of shigellae
A
- Mainly disease of colon, sometimes an initial phase of watery diarrhoea in the ileum
- Bacteria enter mucosal cells via M-cells, ingested by macrophages
- Macrophages killed by apoptosis- release of cytokines- inflammation- tissue destruction
- Actin polymerisation pushes progenies through to multiply
12
Q
Describe clostridium difficile
A
- The most common cause of nosocomial (hospital/ community acquired) diarrhoea, with a severity spectrum ranging from asymptomatic carriage, mild to moderate diarrhoea, to life-threatening pseudomembranous colitis
- Flagella= highly motile
- Gram-positive, spore-forming
- Anaerobic
- Increasingly resistant to antibiotics
13
Q
Describe CDI
A
A spectrum from -Asymptomatic carriage -Diarrhoea/ simple colitis -Pseudomembranous colitis -Fulminant colitis A combination of direct cellular damage and immunopathology -A disease of hospitalised elderly
14
Q
What are the necessary stages in pathogenesis of clostridium difficile?
A
- Colonisation resistance compromised by antibiotics
- Gut becomes susceptible to colonisation by C. difficile
- C. difficile evades immune response and multiplies, producing toxins A and B
15
Q
What is the mechanism of clostridium difficile?
A
- Soluble toxin inside cell by receptor-mediated endocytosis, transfers glucose from UVP glucose
- Translocation from endosome
- Rho and other small GTP-binding proteins glycosylated, GTPases cause collapse
- Cytoskeletal involvement
- Collapse= cytopathic effect
- Rounding with neurite-like protrusions remaining
- Toxins can penetrate into lamina propria= monocytes= TNF, IL8, inflammatory cytokines, neutrophil chemotaxis through tight junctions into gut
