Exam 3 Lecture 24 Flashcards
Obligate anaerobes are killed by:
oxygen
Where are obligate anaerobes found?
everywhere: in our mouth, feces, ubiquitous in soil and silt
Clostridium causes 3 classical diseases, which are:
- gas gangrene
- botulism
- tetanus
Clostridium causes 2 enteric diseases, which are:
- food poisoning
2. antibiotic-associated colitis
Cl. perfringens causes:
- gas gangrene
2. food poisoning
Cl. botulinum causes:
botulism
Cl. tetani causes:
tetanus
Clostridioides difficile (C. diff) causes:
antibiotic-associated colitis
Clostridium natural reservoirs:
soil, intestinal tracts, skin of humans and animals
True or false: Clostridium forms endospores
True
Gram stain of Clostridium
gram positive rods, may see endospores
Why are Clostridium endospores significant?
endospores can survive in the presence of oxygen
Clostridial wound infections are caused by:
mixed clostridial infection following surgery or trauma (Cl. perfringens, other Cl. species)
Gas gangrene
toxins produced by Cl. perfringens causes infection and spreads to healthy muscle tissue; causes myonecrosis
True or false: in gas gangrene, bacteremia is common
false - systemic toxemia can result
What toxins does Cl. perfringens produce to cause gas gangrene?
exotoxins: alpha toxin and perfringolysin O (PFO)
Cl. perfringens alpha toxin is also called:
phospholipase C or lecithinase C
Cl. perfringens alpha toxin function
has phospholipase/spingomyelinase activity which leads to cell lysis (broad spectrum)
Cl. perfringens PFO function
pore forming toxin similar to streptolysin O/listeriolysin O; lyses cells
Cl. perfringens PFO is toxic specifically to:
heart muscle
Cl. perfringens PFO alters ___ ___
capillary permeability
True or false: Cl. perfringens PFO is the principal virulence factor for gas gangrene
false - alpha toxin is principal
Are there host defenses in gas gangrene?
not in necrotic tissues - thus hard to control gas gangrene infection
How is gas gangrene diagnosed?
clinically once typical lesions occur
When is gas gangrene treated?
as soon as typical lesions are clinically identified - treated before lab results come back
Gas gangrene wound pain evolves to ___ and ___
edema and shock
How is gas gangrene treated?
antibiotics, surgical removal of necrotic tissue, oxygenating tissue, possible amputation
True or false: Cl. perfringens divides rapidly which contributes to rapid progression of gas gangrene infection
true - divides once every ~ 6.3 min (faster than E.coli)
True or false: it is common to see lots of white blood cells and PMNs in a tissue sample for gas gangrene
false - altered capillary permeability attributes to no immune cells around infection
True or false: Cl. perfringens often forms spores in gas gangrene infection
false - rarely spores are found
Cl. perfringens on blood agar creates a ____ zone of __ hemolysis.
double; beta
When Cl. perfringens is plated on blood agar, __ causes ____ hemolysis, which is surrounded by ____ hemolysis caused by ____.
PFO causes (beta) complete hemolysis; incomplete hemolysis caused by alpha toxin
Cl. perfringens has ____ activity on egg yolk agar
lecithinase (alpha toxin)
True or false: Cl. perfringens is the 3rd most common cause of food poisoning in the US
True
Source of Cl. perfringens food poisoning
meat products; commercial food preparation
True or false: high inoculum of Cl. perfringens is required to cause food poisoning symptoms
true - 10^6-10^7 viable bacterial cells per gram of food
How does Cl. perfringens cause food poisoning? (3 steps)
- spores germinate during food heating and organisms rapidly increase
- organisms ingested
- organisms sporulate in small intestine and produce enterotoxin
What does Cl. perfringens enterotoxin do?
produces pores in enterocytes, which causes leakage of fluids and ultimately self-limiting diarrhea
Enterocytes
Intestinal absorptive cells
When does onset of symptoms occur for Cl. perfringens food poisoning?
7-22 hours after ingestion of contaminated food
Common symptoms of Cl. perfringens food poisoning
diarrhea, cramps, abdominal pain
True or false: fever, nausea, and vomiting are typically seen in Cl. perfringens food poisoning
false - none of these are typically seen
How can we diagnose Cl. perfringens food poisoning?
- lacks flagella (unlike other clostridia)
2. spores sometimes seen on smears
True or false: regarding Cl. perfringens food poisoning, people rarely seek treatment/care due to quick recovery
true (recovery within 24 hours)
What is the difference between infection and intoxication?
infection = ingestion of live bacteria and establish themselves in the intestine and then produce toxin intoxication = ingestion of preformed toxin in contaminated food
True or false: classical botulism is an infection
false - intoxication
Classical botulism is caused by:
ingestion of preformed toxin in food contaminated with spores sealed in anaerobic environment (mainly improperly canned home food)
Where is Clostridium botulinum found?
soil, silt, vegetation, and intestinal tracts of humans and animals
3 types of botulism
- wound botulism
- infant botulism
- inhalation botulism (isn’t a thing but is a threat)
Wound botulism
usually infection of compound fracture, severe laceration, or penetrating wound. organism is contracted from environment
Infant botulism
caused by germination of spores in intestinal tract of infants 2w-6m of age; adults not affected
Infant botulism can be caused by babies ingesting:
honey (which can’t be sterilized)
Cl. botulinum toxins
7 antigenically distinct types (A thru G)
True or false: all of the Cl. botulinum toxins induce the same neurological disease in humans
True
Mechanism of botulinum toxin
- absorbed in intestine, transported to NMJ via bloodstream
- Ach release from synaptic vesicles is blocked, stopping nerve impulses and impairing motor nerve function
- Paralysis, respiratory failure and death may ensue
Relative toxicity of Cl. botulinum
0.1 - 1 microgram is lethal (2.2 pounds can kill the whole world)
True or false: Cl. botulinum toxin is heat-labile
True - properly cooking food destroys toxin
Cl. botulinum incubation period
12-96 hours (up to 14 days)
duration is related to dose of toxin ingested
Cl. botulinum gastrointestinal symptoms
vomiting, constipation
Other Cl. botulinum symptoms
nervous system-flaccid paralysis
Cl. botulinum mortality rate
20% (declining)
How is Cl. botulinum diagnosed?
clinical isolation of organism from contaminated food/stool sample; pt must be treated before lab results come back
Treatment of Cl. botulinum
- eliminate unabsorbed toxin using stomach lavage and enemas
- eliminate source of toxin
- neutralize unbound toxin using antitoxin
- supportive/respiratory care
How is antitoxin therapy prepared?
7 different antitoxins are made (for each Cl. botulinum toxin); prepared in horses, can result in serum sickness
True or false: antibiotics are not important for treatment except in cases of wound botulism
True
True or false: Cl. tetani produces several different toxins like Cl. botulinum does
False - there are dif serotypes of Cl. tetani but all produce identical toxin
What type of toxin does Cl. tetani produce?
AB toxin
Tetanus pathogenesis
- Cl. tetani spores contaminate penetrating wound
- spores germinate to vegetative cells and produce toxin
- toxin enters motor neurons and is transported to the CNS interneurons
Cl. tetani toxin is transported to the CNS via:
retrograde axonal transmission
In the USA, Cl. tetani has the highest mortality in:
elderly
True or false: the tetanus protein toxin is the sole virulence factor in Cl. tetani
True
Mechanism of tetanus toxin
toxin blocks secretion of inhibitory neurotransmitters between CNS interneurons, causes nonstop muscle flexing
Relative toxicity of tetanus toxin
0.15 to 1 microgram may be lethal for humans
Cl. tetani is gram-___, __ shaped, with ___ ___
gram-positive; rod; terminal endospore
Cl. tetani diagnosis
mainly based on clinical findings: cramping, twitching of muscles around wound, then head and neck
- isolation of organism may be done, tetanus spores are presumptively diagnostic
True or false: for Cl. tetani, early diagnosis is critical for successful treatment
True
True or false: for Cl. tetani, definitive diagnosis requires demonstration of toxin and neutralization with antitoxin
True
Cl. tetani immunity provided by:
DTaP toxoid vaccine - boosters required every 10 years
Cl. tetani treatment (4)
maintenance of airway, Benzodiazepines (GABA antagonists), tetanus immunoglobulin, antibiotics
Tetanus and Botulinum toxins are produced as ___ ____ that accumulate in the ___ until the toxin is released via __ ___
inactive polypeptide; cytosol; cell autolysis
Common mechanism of Tetanus and Botulinum toxin: Active domain transported into ____, specifically cleaves __ of ___ ___, preventing fusion with ___ ___
neuron; VAMP; synaptic vesicle; cell membrane (of post-synaptic neuron)
___ is required to facilitate synaptic vesivle fusion to axon membrane to release neurotransmitter
VAMP (vesicle associated membrane protein)
Which toxins cleave VAMP?
Tetanus toxin, Botulinum Toxins B, D, F, G
C. diff etiology
- mainly nosocomial in following antibiotic therapy
2. normal microbiota is altered, C. diff spores germinate, overgrow, produce toxins, causing colitis
True or false: C. diff is part of the normal microbiota
True
C. diff morphology
slender gram positive rod with large, oval subterminal endospores
True or false: C. diff is resistant to many antibiotics
True
C. diff has _ principal toxins responsible for disease which:
2; disrupt cytoskeletal epithelial cells and submucosal tissue
C. diff toxin A is an _____ and is specific to ____ ____ ___
enterotoxin; intestinal mucosal surface
C. diff toxin B is a ___ ___
generalized cytotoxin
Both C. diff toxins are ___ ____ with __ functional domains
large exotoxins; 3
What are the functional domains of C. diff exotoxin A and B?
- receptor binding
- membrane translocation
- glucosyltransferase activity
Regarding C. diff exotoxins, once in the ___, they inactivate __ ___ by transferring ___ onto them, leading to ____ ___, ___ ____ and ____
cytoplasm; Rho proteins; glucose; cytoskeletal disruption, cell rounding and retraction
C. diff pathogenesis occurs in the ___
colon
Symptoms of C. diff infection include:
abdominal pain, watery diarrhea, mucus or blood may be seen; also red and inflamed colon
True or false: C. diff infection may cause formation of pseudomembrane in the colon
True
C. diff pseudomembrane is characterized as:
1-5mm raised white/yellow plaques on mucosa of colon, composed of epithelial debris, fibrin, and PMN leukocytes
C. diff diagnosis involves: (2)
- demonstration of pseudomembrane via sigmoidoscopy
2. fecal filtrate assays for C. diff toxin (rapid)
How is C. diff treated?
discontinuation of antibiotic therapy, vancomycin or metronidazole, fecal transplant
True or false: C. diff relapse infections are not common after treatment
False - relapse may occur
True or false: C. diff colitis can be spread from person to person
True - may result in outbreaks
In 2003, a ___ ___ ___ of C. diff was isolated. It had a ___ in ___ ___, causing ____ production of toxin A and B.
highly virulent strain; mutation in regulatory gene; increased
Bacteroides fragilis is gram-____ ____ and doesn’t form ___
Negative rod; spores
True or false: there is about 10x as much Bacteroides in the gut as there is E. coli
True
What diseases does Bacteroides fragilis cause?
- intra-abdominal abscesses
2. skin and soft tissue infections (cellulitis and fasciitis associated with surgical wound infection)
B. fragilis virulence factors
has capsular polysaccharides that prevents opsonization, induces abscess formation, promotes adherence to cells
True or false: purified capsular material of B. fragilis can alone cause abscess formation
True
B. fragilis is resistant to:
penicillin
When B. fragilis causes infection, it is often a ___ infection because other anaerobes and facultative bacteria are present
mixed
B. fragilis infection diagnosis
- look for abscesses using radiologic CT and/or aspiration
2. gram stain/culture
Treatment for B. fragilis infection
- 2 antibiotics since most infections and polymicrobial
2. drainage of abscess using CT and needle
