Gastrointestinal Infections Flashcards

1
Q

What percentage of the population is affected by GI infections per year?

A

20%

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2
Q

Where does the GIT span?

A

From mouth to anus

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3
Q

What are the host defence mechanisms?

A
Stomach pH <4
Innate immunity
Digestive enzymes
Peristalsis
Tight junctions between epithelial cells
Commensal microbiota
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4
Q

What environment is the GIT?

A

Anaerobic - strictly anaerobic bacteria outnumbers anaerobes

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5
Q

What are the normal inhabitants of the stomach?

A

Lactic acid bacilli (small number)

Helicobacter pylori

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6
Q

What are the normal inhabitants of the small intestine?

A

Mainly Gram-positive

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7
Q

What are the normal inhabitants of the large intestine?

A

E. coli

Gram-positives (Bacteroides, Clostridium

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8
Q

What are the symptoms of GIT infections?

A
Diarrhoea
Vomiting
Abdominal pain
Nausea
Fever
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9
Q

What abilities does a GI pathogen need?

A
Survive the gastric acid
Attach to epithelium
Get food
Survive in environment
Invade
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10
Q

Which Gram-negative bacteria infect the GIT?

A
Campylobacter jejuni
Salmonella enterica
Helicobacter pylori
Vibrio cholera
Escherichia coli
Shigella spp (sonnei)
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11
Q

How is Helicobacter pylori transmitted?

A

Person-to-person

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12
Q

How does Helicobacter pylori survive in the stimach?

A

Motility- flagella allows it to swim through gastric mucus

Urease - catalyses hydrolysis of urea yielding CO2 and NH3 to raise local pH

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13
Q

What can Helicobacter pylori cause?

A

Gastritis
Gastric ulcer
Gastric cancer

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14
Q

What are the pathogenicity factors of Helicobacter pylori?

A
Urease
Flagella
VacA (pore forming)
Blood group antigen-binding adhesin (BabA)
Type IV secretion system (on cag)
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15
Q

What is T4SS?

A

Transports DNA or protein in Either a 1-step or 2-step mechanism

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16
Q

What do cag strains cause?

A

Stringer inflammatory response in stomach and greater risk of developing peptic ulcers and cancer

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17
Q

What is the most common E. coli strain?

A

K12

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18
Q

What is the infective dose of Enterohaemolytic E. coli?

A

Approximately 10 cells

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19
Q

How does Enterohaemolytic E. coli affect the body?

A

Bloody diarrhoea

Shiga toxin -> haemolytic uraemic syndrome (HUS) -> acute kidney failure

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20
Q

What is shiga toxin?

A

Protein complex encoded by stxAB genes located in prophage
Toxin released from bacterial cell by lysis
Formed from A and B subunits in AB5 complex

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21
Q

What does the A subunit of shiga toxin do?

A

Inhibits protein synthesis after release in host cytosol by removing adenine from 28S RNA of 60S ribosomal subunit

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22
Q

What does the B subunit of shiga toxin do?

A

Cell surface binding to host with Gb3 receptor found mainly on kidney cells

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23
Q

Which toxins have AB family?

A

Shiga

Cholera

24
Q

What are features of Clostridium difficile?

A

Toxin producer
Resistant spores (alcohol hand gel)
Disturbs normal bowel flora
Diarrhoea

25
What are the major toxins of Clostridium difficile?
TcdA and TcdB
26
What do the major toxins in Clostridium difficile cause?
Diarrhoea Inflammation Damage of colonic mucosa
27
How are the toxins of Clostridium difficile internalised to host cell?
Endocytosis
28
How do Tcd toxins work?
Toxin binds to unknown receptor Internalised Enzymic domain proteolytically cleaved from binding domain Endosomes acidified Enzymic component transported to cytoplasm Glucosylates Rho proteins
29
Why is acid resistance an important pathogenicity mechanism?
Survival
30
How does toxin production affect host cells?
Can disable via pore formation in cytoplasmic membrane Disrupt actin cytoskeleton Increase intracellular levels of cyclic AMP Inactivation of signalling pathways (GTPases)
31
What are three types of toxin groups in GI disease?
Neurotoxins Enterotoxins Cytotoxins
32
What are some examples of neurotoxins?
``` Staphylococcus aureus (toxin B) B. cereus (emetic toxin) ```
33
How does a neurotoxin enter the body?
Consumed (intoxication)
34
What is an example of a enterotoxin?
V. cholerae
35
How does V. cholera affect the body?
Direct effect on gut epithelium Water transferred from blood to gut Catastrophic fluid loss
36
What are some examples of cytotoxins?
``` Shiga toxin (Shigella, EHEC) Helicobacter pylori VacA toxin ```
37
What do cytotoxins do?
Destroy intestinal cells | May cause inflammatory diarrhoea
38
What are effector proteins?
Typically enzyme that disrupts host cell signalling pathways for pathogen's benefit
39
How do effector proteins work?
Either by mimicking host endogenous cellular proteins or covalently modifying host cell proteins
40
What are some examples of effector proteins?
E. coli Map | Helicobacter pylori CagA
41
What are the features of a chromosomal genome?
Pathogenicity islands (present in pathogen absent in commensal)
42
What are the features of a mobile genome (mobilome)?
Transmissible (conjugative) plasmids | Phage
43
What are the features of viral GI pathogens?
``` Usually mild gastroenteritis Self limiting Short lived (1-2 days) Person to person transmission/aerosols from vomiting Food bourne outbreaks ```
44
What are the features of noroviru?
``` Winter vomiting disease Affects all ages Low infective dose Aerosol spread Good survival in environment ```
45
Who does rotavirus affect?
Young children <2
46
How can norovirus and rotavirus be detected?
Electron microscopy | PCR
47
What are some examples of protozoan GI pathogens?
Cryptosporidium parvum Giardia lamblia Entamoeba histolytica
48
What is a common feature of Cryptosporidium parvum, Giardia lamblia and Entamoeba histolytica?
Cysts | Often contaminate water surfaces
49
What pathogens would xylose lysine desoxycholate agar be used for?
Salmonella and Shigella spp
50
What is the morphology of Salmonella and Shigella on xylose lysine desoxycholate agar?
Red colonies | Salmonella spp also have black centre
51
How is Salmonella and Shigella differentiated from non-pathogenic bacteria of the same apperance?
Urease test - they are both negative
52
What pathogen is Sorbitol MacConkey agar used for?
E. coli O157 (EHEC)
53
How is E. coli differentiated?
O157 does not ferment sorbitol therefore has pale colonies | Other E.coli ferment sorbitol and therefore have red colonies
54
What is the treatment for most GI pathogens?
Rehydration/electrolyte balance Pain relief (cramps) Antipyretics (fever)
55
What is the therapy for peptic ulcer from Helicobacter pylori?
Calrithromycin or metronidazole | Resistance is common
56
What is the therapy for C. difficile?
Metronidazole | for other diarrhoeal pathogens antibiotic treatment should be avoided - can make worse