6.2 Infections of the Gastrointestinal Tract

Question 1

What are the four types of immune barriers of the gastrointestinal tract?

Answer 1

• Mechanical (e.g. peristalsis)
• Physical (physically blocking invasion of pathogens (e.g. mucous layer)
• Enzymatic (using enzymes to break down pathogens)
• Chemical (altering the chemical environment to kill pathogens)

Question 2

List two reasons why it might be difficult to record the number of gastroenteritis cases in the community

Answer 2

1. Acute, self-limiting disease (gone quickly)
2. Many patients w/ viral gastroenteritis won’t present

Question 3

During which months in Australia are salmonellosis rates higher? Why might that be?

Answer 3

• Summer months
• Undercooked chicken on barbecues

Question 4

How long is the incubation period for campylobacter jejuni? How long does it last?

Answer 4

• 2-4 day incubation period
• Symptoms typically resolve within a week

Question 5

What is a rare disease outcome of bacterial gastroenteritis caused by molecular mimicry?

Answer 5

• Guillain Barre syndrome

(Think: C. Jejuni)

Question 6

Outline the two categories of virulence factors

Answer 6

1. Help establish infection (nutrient scavenging, immunoresistant)
2. Damage host (toxins, inflammatory mediators)

Question 7

What is ID50?

Answer 7

The number of pathogenic organisms required to cause infection in 50% of the population

Question 8

What are the 4 steps in the life cycle of a pathogen? What must the pathogen be able to do to allow this to occur?

Answer 8

1. Transferred to previously-uninfected host
2. Colonisation (adherence/invasion; settling into the niche)
3. Proliferation (cranking the adspend)
4. Transmission to new host (shiny object)

Pathogen must be able to escape host immune system to allow this to occur.

Question 9

What are three routes of transmission for bacteria that cause gastroenteritis?

Answer 9

1. Faecal oral (E. Coli)
2. Zoonotic (cows on the ag farm)
3. Food-borne self inoculation (dodgy chicken)

Question 10

What is the name of the bacterial projections that are important for attachment vs propulsion? A longer version of the attachment one is called…

Answer 10

Attachment: fimbriae
Propulsion: flagellum

Longer version of a fimbriae is a pillus

Question 11

What is the shape of H Pylori? Is it gram neg or gram pos? How many flagella does it have?

Answer 11

• Helix shaped
• Gram negative (negative effect on gastric mucosa)
• 4-6 flagella

Question 12

__ to __ percent of peptic/duodenal ulcers are associated with H Pylori. The mechanism of this is…

Answer 12

• 80 to 90 percent of ulcers are caused by this
• H Pylori uses urease to produce ammonia, neutralising acid and allowing it to survive
• It can then secrete cytotoxins to destroy the layers of the stomach (also increases the ability of the stomach to produce acid, worsening damage, and increases gastrin, causing inc. risk of gastric carcinoma)

Question 13

Why does H Pylori specifically bind in the stomach. Link this to a universal aspect of the bacterial pathogenic life cycle

Answer 13

• It is in the nature of H Pylori’s adhesion molecules to bind to stomach cells
• Just like tissue-specific steroid activation, we see tissue-specific bacterial adhesion

Question 14

True or false: bacterial exotoxins can be shared between bacteria, and are crucial for growth and proliferation

Answer 14

• False
• Yes, they can be shared via DNA sharing…
• But no, they are not required for normal growth

Question 15

What are the two types of exotoxins that bacteria can secrete?

Answer 15

• Cytolysin (what might they do?)
• Two-component toxins: B component Binds, and A component is translocated into the cell, where it’s Actively toxic

Question 16

Describe the pathophysiology of cholera. Causative organism?

Answer 16

• Influences CFTR channel, causing large chloride efflux
• Creates osmotic gradient, pulls other ions into lumen, massive water loss
• Causative organism is vibrio cholerae

Question 17

Which demographic is particularly susceptible to E. Coli infection?

Answer 17

Children under 5

Question 18

How does shiga toxin cause bleeding/thrombi? Why does it affect the kidneys more than other tissues?

Answer 18

• Inhibits endothelial protein synthesis, in dying cells
• Causes bleeding (cell falls away) or microthrombi (in response to cellular injury)
• Receptor for STX is Gb3; expressed highly in kidney vasculature

Question 19

Why does it benefit bacteria to enter host cells? How do they do it?

Answer 19

• Benefit: access to nutrients, evasion of immune system
• Mechanism: inject proteins called invasins to cell to promote endocytosis in cells with no killing abilities (e.g. mucosal epithelium)

Question 20

What are four ways a bacteria can evade apoptosis by host cells once inside a phagosome?

Answer 20

1. Induce apoptosis
2. Escape from phagosome
3. Prevent phagosome fusing w/ lysosome
4. Inactivate host killing mechanisms

Question 21

What is the leading cause of hospital-acquired infectious diarrhoea? What % of people have it in the general population?

Answer 21

• Leading cause is clostridioides difficile
• 2-6% of people in the general population carry it

Question 22

Why does antibiotic use predispose to C Diff? What are the clinical features of C Diff?

Answer 22

• C Diff is more resistant than regular microbiota (this explains why it’s common in hospitals)
• Clinical features range from asymptomatic, to mild diarrhoea, to pancoliits, to toxic megacolon

Question 23

List 3 ways we can diagnose C. Diff

Answer 23

1. Culture
2. Cytotoxicity assay (detect cytotoxins from C Diff)
3. PCR

Question 24

How do C Diff endospores work? How long can they live?

Answer 24

• Provide durable escape pods for cellular components
• Can live for over 20 years (!!!!!!!!!!)

Question 25

C Diff pathogenesis

Answer 25

• Comes out of endospores
• Releases cytokines to recruit immune cells
• Produce yellow, suppurative pseudomembrane

Question 26

Which is more common: bacterial or viral gastro

Answer 26

Viral (by a wide margin)

Question 27

What are 3 features of viruses that can cause gastroenteritis?

Answer 27

• Small but tough
• Rapid disease course
• Extremely good replication

Question 28

List two important viruses that can cause gastroenteritis

Answer 28

• Rotavirus
• Calicivirus

Question 29

Where, geographically, are the majority of rotavirus deaths concentrated? Why?

Answer 29

• Less developed countries (mostly Africa)
• Lack of other vaccines, rehydration therapy etc.

Question 30

How is Rotavirus transmitted?

Answer 30

Faecal-oral (checks out; young kids)

Question 31

How does rotavirus replicate during its lifecycle, and in which kind of cell?

Answer 31

• Enteres enterocytes
• Hijacks cell mcahinery to replicate itself (bringing its own polymerase, since it’s dsRNA)

Question 32

How does rotavirus cause a secretory diarrhoea?

Answer 32

• Enters enterocytes, and released non-structural protein 4 (NSP4)
• Triggers increased release of Ca2+ and water, causing secretory diarrhoea

Question 33

True or false: the innate immune system is our best defense against rotavirus, highlighting the importance of lifestyle changes

Answer 33

• False
• Rotavirus suppresses the innate immune system

Question 34

Epidemiology of norovirus: which environments is it common in, and where does it usually come from?

Answer 34

• Common in schools, nursing homes, planes, cruises etc.
• usually comes from contaminated food or water

Question 35

Norovirus is a type of _____virus

Answer 35

Calicivirus

Question 36

Describe replication of norovirus

Answer 36

• Positive sense ssRNA; can use host machinery
• Encodes polypeptide that is cleaved into structural components for more viruses

Question 37

List 5 types of investigations that can be used to diagnose intestinal infections

Answer 37

1. Faecal microscopy
2. Cytotoxic assays
3. PCR
4. Histology
5. Serology (antibodies)

Question 38

How do we treat bacterial vs viral vs parasitic gastro?

Answer 38

Bacterial: ?antibiotics (sparing)
Viral: Primarily rehydration + antidiarrhoeal agents/antiemetics
Parasitic: antiparasitic agents

Question 39

List 3 emerging approaches for the treatment of gastroenteritis

Answer 39

1. Faecal transplant
2. Probiotics
3. Weaponised bacteriophages (not in use)