L5 CPE, TSST, SpeA Flashcards by Amy Ahern

Is Clostridium perfringens colonising?

No, but live organisms must be consumed. The bacteria sporulate in GIT & produce toxin (CPE)

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What type of toxin does C. perfringens produce?

CPE (Clostridium perfringens enterotoxin) - pore-forming toxin

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What disease is associated with Clostridium perfringens?

Food poisoning

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Are most Clostridia harmless?

Yes

Common in gut

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Describe C. perf

Gram positive, spore-forming, anaerobic rod

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What are the symptoms of a C. perf infection?

cramps, diarrhoea, onset 8-12 hrs, duration 24-36 hrs

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What are common food sources of C. perf?

Large pieces of meat e.g. pork (pig roast), beef
(CPE is sensitive to proteases like trypsin. If you eat lots of protein (i.e. meat) you dilute out the trypsin & it is not longer there to degrade the CPE)

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What may be the cause of >1 million cases of food poisoning in US annually?

Clostridium perfringens

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Why isn’t C. perf a classic intoxication?

Since live cells are involved

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C. perf can produce up to how many different toxins?

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C. perf is classified into __ different toxinotypes based on the production of __ major toxins (alpha, beta, epsilon, iota)

5 different toxinotypes

4 major toxins

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How does CPE work?

CPE binds to host cell → inserts into membrane → fluid loss (enterotoxin)

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What percentage of C. perf strains produce CPE?

Only 5%

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What strain of C. perf does not produce CPE?

Type B

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What is alpha toxin (C. perf)?

membrane-damaging, hemolysin

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What is beta toxin (C. perf)?

membrane-disrupting, pore-forming

halos of lysis form around colonies

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Discuss epsilon toxin (C. perf)?

ETX is the 4th most potent toxin known
Pore-forming
Causes enterotoxaemia
Produced by type B & D strains
Highly lethal disease with major impacts on domestic ruminants
LD50 = 100 ng/kg

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What is special about the iota toxin (C. perf)?

It has ADP ribosylation activity

ADP ribosylates actin - will change actin cytoskeleton of target cell

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What is a binary toxin?

It looks like an A-B toxin but is different
Has 2 components (A & B)
B component involved in binding to host cell & delivering A component to host cell
2 components are produced separately & don’t interact until they find each other on the surface of the host cell
They are not linked by a disulphide bridge
They are not encoded by the same gene

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What is Perfringolysin O, and what does it do?

It is a cholesterol-dependent cytolysin

It forms a pore, which leads to cell lysis

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Where are most of the C. perf toxin genes found?

on plasmids

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What is the binding domain?

C-terminus

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What is the cytotoxic domain?

It carries the cytotoxic activity and inserts into the membrane of the target cell, creating a pore.

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What is the function of complementation?

It controls for rare off-target genetic events that might account for phenotype

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What protein does CPE appear to bind to?

Claudin (important in tight junctions)

Briefly explain the conformational change in claudin (protein) when CPE binds

Protein contracts, cytotoxin domain extends to form a needle-like structure & inserts into membrane of target cell. 6 of those proteins form a hexametric ring - D3 domain from all 6 proteins inserts into membrane - get a clear pore in the membrane through which fluid can leak out

What human disease is primarily associated with C. perf A toxinotype?

Human myonecrosis (gas gangrene) - characterised by its pungent smell of rotting flesh

What is the name for gut rot that is associated with C. perf?

Human enteritis necroticans - often fatal food poisoning

Does human enteritis necroticans most commonly occur in developed or developing countries?

Developing countries

Which toxinotype is gut rot associated with?

Toxinotype C (which has alpha and beta toxins)

What is an example of a food that contains protease inhibitors and increases susceptibility to intoxication by alpha and beta toxins?

Sweet potato

What bacterium is responsible for MRSA?

Staphylococcus aureus

Features of S. aureus & S. pyogenes

Gram positive cocci Non-spore forming Aerobic (require oxygen)

What bacterium produces the toxin that is responsible for Toxic Shock Syndrome?

Staphylococcus aureus

Is TSS exclusively a tampon-associated condition?

No - more recently associated with blisters due to football boots

What happens after colonisation by S. aureus in TSS?

Toxin is produced (TSST-1: toxic shock syndrome toxin)

What bacterium produces the superantigen that is responsible for Toxic Shock Like Syndrome?

Streptococcus pyogenes

Which has a higher death rate: TSS or TSLS?

TSLS

What is produced in TSLS?

A superantigen (SpeA: S. pyogenes erythrogenic toxin)

Differences between S. aureus & S. pyogenes?

S. aureus is non-invasive (bacteraemia is rare) S. pyogenes is invasive (more severe than S. aureus, bacteraemia common) S. aureus never gets into the body - do not get sepsis TSLS - deep site of infection TSS - superficial site of infection

How are TSST and SpeA functionally related?

They both interact with MHC and T cell receptors, but are not similar at the primary sequence level

What happens in TSS?

S. aureus grows in tampon or wound → TSST-1 enters the bloodstream → fever, rash, shock

TSS death rate?

3-6%

TSLS death rate?

>30% | TSLS also termed severe invasive streptococcal disease

What happens in TSLS?

S. pyogenes grows in wound → bacteria enter bloodstream → produce SpeA → fever, rash, shock

What bacterium causes necrotising fasciitis ('flesh eating disease')?

Streptococcus pyogenes

What is necrotising fasciitis characterised by?

The rapid spread of inflammation (intoxication spreads v quickly)

What is the treatment for necrotising fasciitis?

Directly go in and clean the wound (scrape away all dead tissue) or amputate. Antibiotics are too slow

What are the 3 different types of necrotising fasciitis?

Type 1: polymicrobial Type 2: GAS Type 3: gas gangrene

What does acquired SlaA gene encode for?

A phospholipase (a membrane-disrupting toxin)

How does S. pyogenes evade complement?

(i) by producing a C5a peptidase | (ii) surface covered with M protein (immunogenic - switch between ~80 different types) - degrades C3b

Where is SpeA gene located?

On a temperate bacteriophage

Staphylococcal food poisoning

- Common - Vomiting, pain, rapid onset - Foods which are handled, low water activity - Classic intoxication (organism grows on food, produces toxin which is ingested) - Superantigens can cause food poisoning independent of activating T cells - emetic properties, caused by SEs (Staphylococcus enterotoxins)

True or False: Most strains of S. aureus (food poisoning) produce multiple superantigens

True

What are superantigens?

A large family of pyrogenic (fever-inducing) toxins and their roles are variable. All have very similar shapes & interact with MHC & TCRs

What is missing in TSST-1 that is responsible for vomiting reaction?

Particular cysteine loop

Predominant symptoms associated with superantigens?

Vomiting (emesis)

Examples of intoxications (disease without colonisation)?

C. botulinum (A-B toxin), S. aureus (SAg)

Example of a toxicoinfection (disease without colonisation, toxin produced in GIT)?

C. perfringens - causes food poisoning, have to ingest the bacteria in order for the toxin to be delivered to gut

Example of opportunistic (defences breached) pathogens?

- TSS - S. aureus (SAg) - TSLS - S. pyogenes (SAg) - Tetanus - C. tetani (A-B toxin)