Clostriduim Flashcards
1
Q
What is the etiology and epidemiology of Clostriduim?
A
- anaerobic environments
- spore forming bacilli
- ubiquitous in soils as well as intestines of humans and non-humans, commonly found in these areas
- gram-positive
2
Q
Justinian Kerner
A
- Ger.Poet and Physician, 1800’s
- described rod shaped cells (C.botulinum), isolated for spoiled sausage during an outbreak of food poisoning in Wurttemberg, Germany
3
Q
Emile Van Ermengem
A
- Belgian
- Bacteriologist, 1890
- isolated spore-forming bacilli (C.botulinum) from spoiled cured ham, attributed to food poisoning
- this would later be wrongly classified as Bacillus botulinus
- first female research biologist
4
Q
Ida Bengston
A
- American Bacteriologist (NIH)
- in the 1920’s she reclassified Clostridium botulinum
- classified as anaerobic spore-forming bacilli
5
Q
Taxonomy of Clostridium:
- How many species are there?
- What are the ones that are responsible for human disease?
A
- the genus contains approx. 100 species
- C.botulinum
- C.tetani
- C.perfringens
- C.difficile
6
Q
Morphology of Clostridium:
A
- they are spore-forming bacilli
- gram-positive
- endospores
- exopolysaccharide biofilm
7
Q
More Epidemiology of Clostridium:
- Historically, Clostridium is the leading cause of what in soldiers?
- How has these wounds declined overtime?
- Botulinum and tetanus have also declined overtime, what has caused the decline?
- Approx. how many cases per year are there for the two diseases?
A
- wound infections in soldiers
- advancements in prompt, adequate medical treatments (prophylaxis/antisepsis)
- declined in developed nations/ hundreds of cases per year in the U.S., public awareness and widespread immunization are the reasons
- 1,000,000 cases per year for each
8
Q
More questions about Clostridium:
- Clostridium can be both _____ and ____.
- What are some routs of entry for Clostridium?
- What are most Clostridium characterized by?
A
- 1 obligate 1.2 opportunistic pathogens
- Routs of entry include both ingress (ingestion) and parenteral (wounds)
- characterized by acute, toxin-associated infections and are non-invasive
9
Q
Nosocimial disease in Clostridium:
- What species of Clostridium are nosocomial?
- How is it transmitted?
A
- C.difficile
- hospital-acquired opportunistis (5000,000 per year in U.S.)
- transmitted via fecal-oral route however, carriage rates are low in adults
- can inhabit the gut asymptotically, low carriage rate, maybe a patient is being treated for MRSA and is on antibiotics
- antibiotics will clear the MRSA, but the immune diffidence is low, exposed to C.difficile from nurse/doctor via fecal-oral route
- C.Diff can be established in the gut of patient asymptomatically, he is a new carrier, transmits C.diff disease in the community, came in with one infection but left with another
10
Q
Fill in the blank: Clostridium infections are associated with a_______- nearly all are ____.
A
- broad spectrum of human disease
2. toxin-associated
11
Q
Answer these questions about Clostridium toxin-associated disease:
1. Neurotoxic clostridium is associated with…?
A
- C.tetani
2. C.botulinum
12
Q
Answer these questions about Clostridium toxin-associated disease:
2. Enterotoxemic and Enteropathogenic clostridia is associated with…?
A
- C.perfringens type A-E
2. C.difficile
13
Q
Answer these questions about Clostridium toxin-associated disease:
3. Histotoxic clostridia is associated with…?
A
- C. perfringens and the other ones, whatever
14
Q
The Big 4! C.perfringens:
1. What does it infect and what does it present as?
A
- targets soft tissues of the dermis as well as muscle and organ systems— presents as gas gangrene and cellulitis
- attacks the gastrointestinal system— an agent of food poisoning
- also presents as narcotizing enteritis, hemorrhagic inflammatory infection of the small bowl, sepsis
- etiologic symptom, [alpha]-toxin
15
Q
The Big 4! C.perfringens:
- Where can C.perfringens become established and what can it do once established?
- What does multiplication and toxin production lead to?
A
- it can become established in anaerobic wounds, it impaired blood supply due to trauma and occlusion favors growth
- multiplication and toxin production (collagenases, lipases, proteases and hemolysins) leads to rapid tissue necrosis
- prognosis is grim and infections can be fatal
16
Q
Connect the presentation to the bacteria and the toxin that causes it:
- C.perfringens?
- C.botulinum?
- C.tetani?
- C.difficile?
A
- C.perfringens—- gas gangrene, cellulitis, food poisoning, narcotizing enteritis and sepsis (alpha toxin)
- C.botulinum—botulism (botulinum toxin, BoNT)
- C.tetani—- tetanus (tenanospasmin, TeNT)
- C.difficile—pseudomembranous colitis ( ToxA/ToxB)
17
Q
Answer these questions regarding Clostridium toxins:
1. The difference between all of the big 4 is determined by what?
A
- production of toxin
18
Q
Answer these questions regarding Botulinum toxin:
- What toxin is botulinum caused by and what are its clinical symptoms?
- What are the 3 forms of botulism and what do they do in the body?
A
- Botulism is caused by the bacteria C.botulinum neurotoxin (BoNT), causes a symmetrical, descending paralysis, death is due to cardiac/pulmonary failure
- there are 3 forms of Botulism
- Adult– caused by ingestion of preformed toxin;toxinosis
- Infant– replication and toxin production in the intestine
- Wound botulism– replication and toxin production in wounds
19
Q
Answer these questions regarding Botulinum toxin:
- How deadly is BoNT? How many BoNT toxins are there and which one has the highest mortality?
- BoNT disseminates in the blood and lymphatics to do what?
- What type of dichain does BoNT have?
- What are the 3 functional domains of the dichain?
A
- very potent toxin, the lethal dose (LD50) >40ng, at least 8 immunogenetically distinct BoNT toxins, Only [A, B, E] are clinically relevant, Mortality highest for A, this id due to receptor affinity
- to cranial and then to peripheral nervous tissues
- large A-B dichain (ca 150kDa) neurotoxin
- Heavy C-terminal chain (Hc)— neurospecific binding
- Heaby N-terminal chain (Hn)—- translocation of HL
- Light chain (Lc)– is a protease
20
Q
Explain the mechanism for BoNT:
A
- Neurospecific binding of BoNT and receptor-mediated endocytosis is achieved by HC domain
- BoNT will then bind to SNAP-25 (synaptosomal-associated protein receptors) on neurons, this will result in receptor-mediated endocytosis
- The Hn domain will then fuse with the endosome membrane to form the HL domain (a pore-like translocation domain), this domain is moved through the pore into the host cell cytoplasm
- Normal neuromuscular junctions? host SNARE proteins deliver synaptic vesicles that have acetylcholin to the synaptic cleft
- the LC protease subunit of BoNT cleaves SNARE proteins, this prevents delivery of synaptic vesicles to the junction, leads to muscle fibers to become paralyzed
21
Q
Answer these questions about TeNT:
- What neurotoxin causes tetanus and what are its clinical symptoms?
- How does C.tetani enter its host and what does it do one entered through the host? What can this lead to?
A
- tetanus is caused by C.tetani tetanospasmin (TeNT), clinical symptoms are trismus (lockjaw), extreme muscle rigidity, painful spasms (opisthotonos), one inside the host it will replicate and produce TeNT
- it enters its host parenterally through breaks in the skin [ dog/pig bite, gunshot, dirty needles, barbed wire, puncture wounds form nails], this can eventually lead to cardiac/pulmonary failure
22
Q
Answer these questions about TeNT:
- What type of dichain does TeNT have? Is TeNT as toxic as BoNT?
- What does TeNT interfere with in the body?
- What is GABA?
A
- TeNT has a A-B dichain, similar structure to BoNT, it is however less toxic (LD50– 100ng)
- it interferes with the delivery of y-amino butyric acid (GABA) neurotransmitter to neuromuscuar junctions in nerve synapses
- GABA is an inhibitory neurotransmitter, it blocks the release of acetylcholin (muscle contraction) at neurotransmitter junctions
23
Q
Explain the mechanism for TeNT pathogenesis:
A
- TeNT light chain (Lc) protease targets the SNARE protein synaptobrevin, this normally delivers GABA containing inhibitory vesicles to the junction
- this will lead to spasms, muscle rigidity, convulsion, death
- Tetanus toxin prevents the release of glycine and GABA, prevents relaxation of muscles
24
Q
What is the main difference between TeNT and BoNT?
A
- BoNT leads to the blockage of the release of acetychlorine, prevents muscle relaxation
- TeNT leads to uncontrolled release of acetylcholine, stopping muscle contraction
25
Q
Answer these questions about C.Difficile:
- Where is C.diff found naturally?
- What type of antibiotics permits intestinal growth?
A
- C.diff is found naturally in the intestinal microbiota in a small percentage of healthy adults, it is also found naturally in the environment
- Broad spectrum antibiotic therapy can permit intestinal growth
26
Q
Answer these questions about TcdA/TcdB in C.diff:
- Some strains of C.diff produce varying amounts of certain enterotoxins. What are these enterotoxins and what are their clinical symptoms?
- Both TcdA/TcdB are what? And what can this cause?
A
- C.diff produces varying amounts of enterotoxin ToxA (TcdA) and cytotoxin ToxB (TcdB), the main clinical symptoms are secretory diarrhea and inflammation, determined by sequelae of psudomembraneous colitis
- both are cytotoxic, this causes disruption of the actin cytoskeleton and tight junctions, this will later lead to fluid accumulation and destruction of intestinal epithelium
27
Q
TcdA/TcdB question:
1. What are the four functional domains of TcdA and TcdB?
A
- GTD– glucosyltransferase
- APD– autoprotease
- Delivery–translocation
- CROPS– receptor binding, [combined repetitive oligopeptides] domain
28
Q
Explain the TcdA pathogenesis:
A
- TcdA binds to CROPS receptors, internalized by receptor-mediated endocytosis
- Delivery/translocation domain fuses with endosome membrane
- GTD domain is then translocated through the delivery domain, then released into the host cytoplasm
- GTD glucosylates Rho family GTPases– altering signal transduction and causing dysregulation of cytoskeleton, Tj loosening and inducing apoptosis
- TcdA/B cytotoxicity and immune-stimulation leads to psudomembrane formation and colitis in the large bowl
29
Q
Answer these questions about diagnosis of Clostridium:
- Diagnosis of wound infections is based on what?
- C.diff diagnosis is based on symptoms in conjugation with antibiotic chemotherapy. What does a colonoscopy show?
- Early diagnosis is important. Why is this?
A
- wound infections (C.perfringens) based on clinical syndrome, direct microscopic exam with gran reaction/culture of wound exudates
- C.diff diagnosis, culture from stool, colonoscopy is required for diagnosis of psudomembranous colitis
- various diseases share similar symptoms on tetanus (C.tetani) and botulism (C.botulinum) [rabies, meningitis, stroke, overdose], early diagnosis is crucial for positive prognosis
30
Q
Answer these questions about diagnosis of Clostridium:
- What would be included in a C.botulinum diagnosis?
- What CDC/FDA test can show the presence of C.botulinum?
A
- diagnosis includes brain scans, nerve conduction (NCS) examination of spinal fluid (spinal tap), validate by detection of BoNT in serum and exudates
- approved an ELISA immunoassay for lab conformation of BoNT [A, B, E, F] directly from clinical samples
31
Q
Answer these questions about prevention of Clostridium:
- What can prevent food-bore botulism?
- Are there any vaccines for any of the bacterial types?
- What can help with the prevention of C.diff infection?
A
- adequate food preservation methods, heat all canned food before eating
- toxoid-based vaccines against tetanus, DTaP and TdaP
- prudent practice in prescribing broad-spectrum antibiotics for high-risk patients, patient isolation, environment decontamination could mitigate further nosocomial spread
32
Q
Answer these questions about therapy of Clostridium:
- What is botulism treated with? What do the antibodies do to BoNT?
- What antibiotics can be used for C.diff? What about probiotics? Reoccurring infections?
A
- treated with antibody immunotherapy- HBAT- composed of antibodies that are able to neutralize BoNT in tissues
- for C.diff, metronidazole, vancomysin, fidaxomicin, probiotics/immunotherapy limited in efficacy, reoccurring infections lead to the use of fecal microbiota transplantation
