Clostridia Flashcards
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
C) Gram(-), rod Shaped, endospore-formers, anaerobes
Where is Clsotridia found?
Soil and Intestinal tracts of animals
How many species of Clsotridia are there and what imoprtant human pathogens include?
>80 species
C. difficile - pseudomembranous colitis
C. tetani - tetnus
C. botulinum - botulism
C. perfringens - food-borne illness and gas gangrene
What is the primary virulent factor?
Exotoxins
What advantages do endospores have?
Highly resistant to heat, drying, harsh chemicals and nutrient depletion
Survival structures, also used for dispersal
Why does spore formation occur?
- 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)
What is the spore made of?
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
Does pasteurization(63-72 oC) kill endospores?
No autclaving (121 oC) will
C. difficile (diff) causes pseudomembranous colitis (also called antibiotic-associated diarreah) this can exist as what?
Asymptomatic carrier state
Cause of mild to moderate diarrhea
Cause of life-threatening pseudomembranous colitis
How is C. diff transmitted?
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
What % of healthy adults are colonized?
~3%, C. diff can be harboured in the large intestine in low #s
What is the most important risk factor of pseudomembranous colitis?
Why is this important?
- 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
What does the A and B domain designate in the A-B toxins produced by C. diff and what are these toxins called?
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
How does the A domain inactivate G proteins of host cells and what is the significance of G proteins?
G proteins are key regulatory proteins
A domain causes disregulation of multiple cell processes including cytoskeletal rearrangements -> cell death and inflammation
Study that a bit
What are the symptoms of pseudomembranous colitis?
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
what does the pseudomembrane in pseudomembrane colitis stand for?
The lesions can enlarge to cover substantial portions of inflamed mucosa and can be stripped off
What is the Diagnosis and treatment of C. diff?
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)
What is a fecal microbiotia transplantation?
Restoration of stable healthy guy microbiota
What does C. tetani cause and where is it found?
Causes tetnus (also called lockjaw)
Found in soil and intestinal tracts of various animals
What is the tetnus toxin?
an A:B neurotoxin
What are the symptoms of tetanus?
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
Is the tetanus vaccine protective?
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
How is C. tetani caused?
colonization of deep wound (Stepping on a rusty nail)
Anoxic conditions are required for growth and toxin production
Untreated tetanus has a high moratilty
What type of toxin does tetanus produce and what are its effects?
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
What is toxic paralysis?
Toxins enter at neuromuscular synapse and migrates retrogradely inside the motor neuron to the spinal cord where it blocks inhibitory neurons
How is C. botulinum (causes botulism) transmitted and how is it destroyed?
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
Where is C. botulinum found? what toxin does it make and is there a vaccine?
Organisms found in soil and GI tracts of animals
Produces botulinum toxin (A:B neurotoxin)
An experimental vaccine exists (not widely used)
What are symptoms of food borne botulism?
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
What is infant botulism?
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
What is wound botulism?
C botlinum infecting a wound (not common)
Whtt does the botulinum toxin do?
Causes flaccid paralysis
blocks release of acetylcholine at neuromuscular junctions
enters at neuromuscular synapse and acts at the neuronal terminal to black ACh release
What is the difference between tetanus toxin and botulinum toxin?
The toxins target the same key molecules of the presynaptic region, but act at different locations to produce completely different disease
Descibe C. perfringens
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
What are symptoms of C. perfingens?
– 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)
What does C. perfringens cause other than food poisoning?
Gas gangrene
How does gas gangrene occur?
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)
What is the key virulence factor in C. perfringens?
alpha-toxin
What are symptoms and causes of gas gangrene?
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
How does the alpha toxin from C. perfringens work?
a phospholipase damages membranes - removes the head groups from phospholipids
results in inflammatino and damage reduces blood flow lowering O2
How do you treat the symptoms of necrosis in C. perfringen gas gangrene?
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)
