6 - Toxins and Anaerobes Flashcards

1
Q

What are properties of a successful pathogen? What are the two mechanisms of pathogenesis?

A
  1. Gain access into the host
  2. Colonize the host
  3. Resist host defense mechanisms
  4. Damage host

Two mechanisms of pathogenesis: invasiveness and toxigenicity.

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2
Q

What are characteristics of anaerobic bacteria/anaerobic infections?

A

Located on mucosal surfaces, infections are mixed, opportunistic infections, and include either/both aerobic or anaerobic bacteria.

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3
Q

How do anaerobes deal with oxygen/oxygen radicals? What are they sensitive to?

A

They are sensitive of O2 intermediates and have superoxide dismutase to remove O2 radicals

Have low amounts of catalase to remove H2O2

Often lack cytochromes and use fermentation.

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4
Q

What are the sites of infections of anaerobic gram negative pathogens? How would you describe these infections?

A

Colon (intra-abdominal abscess) mouth, skin. Foul-smelling.

Gas producing (diagnostic).

Poly-microbial nature of anaerobic infections.
Void of aerobic bacteria (anoxic).

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5
Q

What is a common gram - anaerobic pathogen that causes most intra-abdominal infections? What are characteristics of type of bacterial infection?

A

Bacteriodes fragilis: some are more virulent than others, some produce capsules.

Aerotolerant and encode two major oxidative stress response genes: catalase and superoxide dismutase.

Often isolated in mixed bacterial infection with other anaerobes (like peptostreptococcus)

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6
Q

What is the appearance of bacteroides fragilis? How can it be grown selectively out of the gut?

A

Pleomorphic: extended bacteria in the culture

Gram negative bacilli.

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7
Q

How can bacteroides fragillis be grown selectively out of the gut?

A

On bile-esculin agar with gentamicin, because most other bacteria (aerobic and anaerobic) are inhibited by bile and gentamicin.

Appears black on this plate due to its degradation of esculin.

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8
Q

Sites of infection are _____ and ______ infections are common.

A

Pathogen-specific

Mixed infections are common

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9
Q

What types of pathogens are associated with surgical site infections in cardiac surgery patients?

A

Gram + organisms (48%)

Gram negative organisms (40%)

Fungi (12%)

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10
Q

What are the characteristics of clostridia? Where are they commonly found? What are the two different types of pathogenesis found?

A

Anaerobic gram + spore forming bacilli; obligate anaerobes or aerotolerant.

Pathogenic due to invasiveness or producing an exotoxin.

Inhabitants of soil and the intestinal tract.

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11
Q

Which type of clostridia is invasive? What is it’s mechanism of action?

A

C. perfringens

Alpha toxin with phospholipase that damages tissue

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12
Q

Which types of clostridia produce toxins? What does each produce and what type of disease is each associated with?

A

C. difficile: GI disease - produces toxin A and B

C. tetani: tetanus - tetanuc toxin

C. botulinum: botulism/food poisening - botulinum toxin

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13
Q

Which type of clostridia is histotoxic and causes extensive destruction of muscle and connective tissue and is characterized by the formation of gas? What predisposes someone to this?

A

C. perfringens: produces alpha toxin and causes most clostridial-mediated myonecrosis.

A deep wound to muscle predisposes someone.

Can cause gas gangrene and requires antibiotic treatment and sometimes amputation.

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14
Q

How does C. perfringens cause tissue damage?

A

It reduces tissue redox potential causes host cell death.

Uses nutrients from host proteases for growth.

Produces alpha toxin (phospholipase) that causes tissue damage.

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15
Q

What are the four types of bacterial toxins?

A
  1. Surface-acting toxins
  2. Pore-forming toxins
  3. A/B toxins
  4. Type III and IV secretion
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16
Q

What are general characteristics of bacterial toxins?

A

Have a catalytic component (enzyme) that modifies specific host macromolecules (post-translational modification)

and host cell binding component that’s tissue specific (such as clostridial neurotoxin) or non-tissue specific (diptheria toxin).

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17
Q

What is the modification associated with diptheria toxin and pseudomonas aeruginosa exotoxin A?

A

ADP-ribosylation of elongation factor-2 (EF2), causing inhibition of protein synthesis.

18
Q

What is the modification associated with botulinum toxin and tetanus toxin?

A

Protease for SNARE proteins inhibits nt vesicle fusion to the cell membrane.

19
Q

What is the modification associated with large clostridium difficile toxins?

A

Glucosylate Rho proteins; inhibits cell motility and ultrastructure via active modification.

20
Q

What is the modification associated with shiga toxin?

A

Deadenylates an adenenine on RNA; inhibits protein synthesis.

21
Q

You can prevent some bacterial diseases by vaccination with _____ .What are two example of this?

A

Toxoids which are chemically inactivated toxins.

DT/TT vaccine is formalin inactivated diptheria/tetanus toxin.

Conjugate vaccines: Hib polysaccharide conjugated to diptheria toxoid to make a T-dependent immune response with IgG and memory.

22
Q

What can C. difficile cause?

A

Antibiotic associated diarrhea (gastrointestinal colitis).

When taking antibiotics, C. diff can overcome intestinal flora and produce toxin A and B with glucosylate Rho GTPases which disrupts gut epithelia to cause diarrhea and inflammation.

23
Q

Emergency of highly toxic stain of C. diss resistant to ______ has caused outbreaks in the US and Canada.

A

fluoroquinolones.

24
Q

What is the difference between C. tetani and C botulinum?

A

Both produce neurotoxins.

C. botulinum has no vaccine and causes flaccid paralysis, while C. tetani has a licenced vaccine and causes spastic paralysis.

25
Q

What are the different clostridial neurotoxin serotypes associated with botulinum toxin and tetanus toxin?

A

Most toxic protein toxins for humans.

Botulinum has 7 serotypes: A, B, C, D, E, F, and G defined by antisera neutralization.

Tetanus toxin: single serotype (easier to make vaccine for).

26
Q

What is the mechanism of action of clostridium neurotoxins?

A

They are proteases that cleave SNARE proteins and inhibit synaptic vesicle fusion.

27
Q

Botulinum toxin (BoNT) and tetanus toxin (TeNT) both do what?

A

Both cleave the same catalytic activity and cause SNARE cleavage.

But they cause different diseases, so we know that the SNARE cleavage does not define the spasticity of each toxin.

28
Q

How is it possible that both BoNT and TeNT have the same mechanism of action but produce different effects?

A

Their unique pathologies are due to intracellular trafficking.

BoNT has peripheral action at the MN, yielding an inhibition of Ach release at the NMJ (flaccid paralysis)

Tetanus toxin does retrograde trafficking to inhibitory interneuron and stimulates Ach release at the NMJ (spastic paralysis).

29
Q

What is the physiology os C. tetani? How does intoxication occur?

A

Anaerov\be that has proteolytic action.

Not invasive, remains at the site of infection and produces tetanus toxin.

Following injury with mixed bacterial infection, soil bacteria ferment to reduce redox potential which allows growth of C. tetani sufficient for toxin production.

30
Q

Describe the preventative vaccines for tetanus? Describe the nomenclature.

A

Prevents diptheria, tetanus, and pertussis: DTaP, Tdap, DT, and Td.

Upper-case letters are full strength doses of dioptheria (D) and tetanus (T) toxoids and pertussis (P)

Lower-case “d” and “p” are reduced doses of doptheria and pertussis, “a” in DTaP stands for acellular (meaning that the pertussis component contains only a part of the organism).

31
Q

At what age are DTaP, Tdap, DT, and Td each given?

A

DTaP and DT: children younger than 7 yrs

DTaP: 5 doses at 2, 4, 6, and 15-18 mo, and 4-6 yrs.

Tdap and Td given to older children and adults

32
Q

What should be given with a suspected case of tetanus?

A

Vaccinate Td or Tdap: stimulates an Ab response to toxin

Antibiotics to inactivate the bacteria

Administer anti-TT antibody (passive immunity): neutralized circulating toxin

33
Q

What natural disease is associated with C. botulinum intoxication (from food)?

A

Toxin in bloodstrem attacks neurons and causes flaccid paralysis.

34
Q

What natural diseases are associated with C. botulinum infection?

A

Infant botulinum: spores ingested and grow in GI tract, eventually toxin causes flaccid paralysis.

Wound botulism: C. botulinum spores in wound grow and produce toxin, eventually causing flaccid paralysis.

35
Q

What is the pathogenicity associated with botulinum toxin?

A

Froduces AB toxin, has zinc proteases, inhibits nt release causing flaccid paralysis.

36
Q

What is each botulinum serotype (A-G) defined by the absence of? Which serotypes are the most common natural forms for humans?

A

Absence of cross-neutralization by serotype specific antisera.
-for exp. only antiBT/A antisera neutralizes BT/A

A, B, E, and F most common in humans

37
Q

What are botulinum toxins A and B used for therapeutically? What makes these good for drug therapies?

A

Serptype A: botox used to treat wrinkles

Serotype B: Myoboc used to treat cervical spasms

They have longevity inside of the host making them a potent drug therapy for human neurological diseases.

38
Q

Are botulism and botulinum toxin contagious? Can they be transmitted from person to person? What can they be used for?

A

No and No.

Implicated as an agent of biological warfare b/c it’s the most potent protein toxin for humans lethal at ~1 microG/adult

39
Q

Since there’s no licensed vaccine, what is the treatment for botulism? What do people at the CDC and in the army get?

A

Passive immunization with anti-BoNT antibody.

At risk personnel get horse derived anti-sera (must consider hypersensitivity)

CDC: anti-A,B,R sera
US army: A-G sera

40
Q

What is done to reduce the hospital stay of infants with botulism?

A

Infact botulism types A and B get babyBIG or BIG-IV which are botulism IVIgs.

Human-derived anti-botulism toxin antibodies to serotypes A and B.

41
Q

Why are BoNTs clinically useful?

A

Due to neuron specificity:

  • bind receptors on neurons
  • cleave neuronal SNARE substrates
  • therefore, limited off target effects
42
Q

What condition can BoNTs treat?

A

Blepharospasm: abnormal contractino or twitch of the eyelid neurons (functional blindness)

  • BoNT cleaves snare proteins in spastic nerves to relieve spasticity
  • long1/2 life in neurons (months long therapy per injection)