Clostridia

Question 1

Is Clostridia

A) Gram(-), coccus shaped, endospore-formers, aerobes

B) Gram(+), rod shaped, exospore-formers, anaerobes

C) Gram(-), rod Shaped, endospore-formers, anaerobes

D) Gram(-), coccus shaped, exospore-formers, aerobes

Answer 1

C) Gram(-), rod Shaped, endospore-formers, anaerobes

Question 2

Where is Clsotridia found?

Answer 2

Soil and Intestinal tracts of animals

Question 3

How many species of Clsotridia are there and what imoprtant human pathogens include?

Answer 3

>80 species

C. difficile - pseudomembranous colitis

C. tetani - tetnus

C. botulinum - botulism

C. perfringens - food-borne illness and gas gangrene

Question 4

What is the primary virulent factor?

Answer 4

Exotoxins

Question 5

What advantages do endospores have?

Answer 5

Highly resistant to heat, drying, harsh chemicals and nutrient depletion

Survival structures, also used for dispersal

Question 6

Why does spore formation occur?

Answer 6

• Due to lack of nutrients or stress
• Dormant phase in the bacterial life cycle
• endospores can remain dormant for years but revert back to vegetative cells rapidly (within minutes)

Question 7

What is the spore made of?

Answer 7

Exosporium and spore coat are composed of protein, core wall is peptidoglycan, the cortex contains DNA, cytoplasm, ribosomes, etc

Dipicolinic acid complex with Ca++ helps to dehydrate the cortex (consistency of a gel, but very resistant to heat, etc

Question 8

Does pasteurization(63-72 ^oC) kill endospores?

Answer 8

No autclaving (121 ^oC) will

Question 9

C. difficile (diff) causes pseudomembranous colitis (also called antibiotic-associated diarreah) this can exist as what?

Answer 9

Asymptomatic carrier state

Cause of mild to moderate diarrhea

Cause of life-threatening pseudomembranous colitis

Question 10

How is C. diff transmitted?

Answer 10

spores: fecal-oral route
- can be difficult to eradicate from environment (cultured from floor, bed pans, toilets, hands and clothing of medical personel)
- Noscomial pathogen

Question 11

What % of healthy adults are colonized?

Answer 11

~3%, C. diff can be harboured in the large intestine in low #s

Question 12

What is the most important risk factor of pseudomembranous colitis?

Why is this important?

Answer 12

• Most sympromatic patients have recently recieved antimicrobial agent
• Antibiotics kill normal microbiota, but C. diff enters endospore state
• suppression of normal flora + persistence of C. diff endospores
• After the antibiotic is stopped, spores germinate, overgrowth of C. diffi occurs with production of toxins which damage the intestinal lining of the large intestine

Question 13

What does the A and B domain designate in the A-B toxins produced by C. diff and what are these toxins called?

Answer 13

Called: large clostridial cytotoxins

A domain: active portion of the toxin that carries the enzymatic activity

B domain: denotes the portion of the toxin molecule responsible for binding and uptake by the host cell

Question 14

How does the A domain inactivate G proteins of host cells and what is the significance of G proteins?

Answer 14

G proteins are key regulatory proteins

A domain causes disregulation of multiple cell processes including cytoskeletal rearrangements -> cell death and inflammation

Question 15

Study that a bit

Answer 15

Question 16

What are the symptoms of pseudomembranous colitis?

Answer 16

Offensive smelling diarrhea, abdominal pain, fever, nausea, dehydration, “constitutional symptoms”

Serious sympotoms: low blood pressure, kidney failure, perforated colon, toxic megacolon, yellow lesions in endoscopy

• symptoms may occur 1-2 days after antibiotics or several weeks after

Question 17

what does the pseudomembrane in pseudomembrane colitis stand for?

Answer 17

The lesions can enlarge to cover substantial portions of inflamed mucosa and can be stripped off

Question 18

What is the Diagnosis and treatment of C. diff?

Answer 18

History of antibiotic use, symptoms and lab tests can confirm

endoscopy and toxin detection assays

Discontinue inciting antibiotic if still being used

fluids

Antibiotics more specific for C. diff (oral vancomycin or I.V. metronidazole)

Avoid antidiarrheal aganets (colonic stasis = build up of toxins)

Question 19

What is a fecal microbiotia transplantation?

Answer 19

Restoration of stable healthy guy microbiota

Question 20

What does C. tetani cause and where is it found?

Answer 20

Causes tetnus (also called lockjaw)

Found in soil and intestinal tracts of various animals

Question 21

What is the tetnus toxin?

Answer 21

an A:B neurotoxin

Question 22

What are the symptoms of tetanus?

Answer 22

descending pattern of muscle spasms

incubation period of 3 days to 3 weeks

lockjaw, stiff neck, wallowing dificulties, chest muscles, etc.

spasms can last several minutes

Question 23

Is the tetanus vaccine protective?

Answer 23

yes the tetanus toxoid vaccine is protective (part of the TDaP vaccine)

tetanus still remains a problem in developing countries where immunization is not widely practiced

Question 24

How is C. tetani caused?

Answer 24

colonization of deep wound (Stepping on a rusty nail)

Anoxic conditions are required for growth and toxin production

Untreated tetanus has a high moratilty

Question 25

What type of toxin does tetanus produce and what are its effects?

Answer 25

A:B toxin

A domain is a protease that cleaves proteins in nerve terminals in the CNS

prevents release of neurotransmitters

causes spastic paralysis

if respiratory muscles are involved, death by asphyxiation

Question 26

What is toxic paralysis?

Answer 26

Toxins enter at neuromuscular synapse and migrates retrogradely inside the motor neuron to the spinal cord where it blocks inhibitory neurons

Question 27

How is C. botulinum (causes botulism) transmitted and how is it destroyed?

Answer 27

Food borne intoxication

Toxin is preformed in foods

results from eating undercooked foods where endospores have germinated and produced toxin

botulinum toxin is destroyed by heat

requires anoxic conditions for growth

causes flaccid paralysis that can exist for weeks to months

Question 28

Where is C. botulinum found? what toxin does it make and is there a vaccine?

Answer 28

Organisms found in soil and GI tracts of animals

Produces botulinum toxin (A:B neurotoxin)

An experimental vaccine exists (not widely used)

Question 29

What are symptoms of food borne botulism?

Answer 29

Symptoms start 18=36 hours after ingestion

Weakness, dizzyness, dry mouth

Blurred vision, swallowing problems, weakness of skeletal and respiratory muscles, death can occur by asphyxiation

Question 30

What is infant botulism?

Answer 30

due to infectino by C. botulinum

typically occurs in young infants exposed to solid foods

lack of competing intestinal microbiota

organisms colonize and produce toxin leading to botulism

lethargic, eak, porr feeding, constipation, poor muscle tone

Question 31

What is wound botulism?

Answer 31

C botlinum infecting a wound (not common)

Question 32

Whtt does the botulinum toxin do?

Answer 32

Causes flaccid paralysis

blocks release of acetylcholine at neuromuscular junctions

enters at neuromuscular synapse and acts at the neuronal terminal to black ACh release

Question 33

What is the difference between tetanus toxin and botulinum toxin?

Answer 33

The toxins target the same key molecules of the presynaptic region, but act at different locations to produce completely different disease

Question 34

Descibe C. perfringens

Answer 34

widely distributed in the environment and found in the intestinal tracts of animals
• a common cause of food-borne illness

– endospores survive cooking process

– usually meat products are implicated

– food undergoes “temperature abuse” – left at > 4°C or < 60°C

– illness generally lasts 24 h

Question 35

What are symptoms of C. perfingens?

Answer 35

– requires ingestion of large numbers of bacteria (~ 107)
– intense abdominal cramps and diarrhea 18-22 hours after ingestion
– C. perfringens produces an enterotoxin in the intestinal tract that is
responsible for the illness (not a ‘preformed’ intoxication)

Question 36

What does C. perfringens cause other than food poisoning?

Answer 36

Gas gangrene

Question 37

How does gas gangrene occur?

Answer 37

Results from clostridial infection (especially perfringens)

survive and multiply only in tissues where there is a low oxygen tension

usually a dirty wound is infected which has been closed without adequate debridement

Toxins produced by organisms destroy the cell membrane and rapidly lead to tissue necrosis (producing disease spread)

Question 38

What is the key virulence factor in C. perfringens?

Answer 38

alpha-toxin

Question 39

What are symptoms and causes of gas gangrene?

Answer 39

infectino produces gas within the tissues

gangrene is a type of necrosis due to lack of blood supply

probably requires low O₂ due to tissue damage

May have short <24h or long >week onset but is sudden and traumatic

skin turns yellow _> bronzing -> blue/black necrosis

extreme pain

decreased pain could mean nerves are being destroyed

Question 40

How does the alpha toxin from C. perfringens work?

Answer 40

a phospholipase damages membranes - removes the head groups from phospholipids

results in inflammatino and damage reduces blood flow lowering O₂

Question 41

How do you treat the symptoms of necrosis in C. perfringen gas gangrene?

Answer 41

Patient can develop serious symptoms

fever, low bp, decreased urine output

mortality due to shock and renal failure

treatment must be rapid

antibiotics have trouble penetrating due to ischemia

may involve debridement and drainage (possible amputation)