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346 Cards in this Set
- Front
- Back
Clostridium:
gram stain? morphology? |
Clostridium:
gram (+) spore-forming rod |
|
Clostridium:
Aerobe/Anerobe? Facultative/Obligate? |
Clostridium:
Obligate anaerobes (but some strains can tolerate oxygen) |
|
Clostridium spores are highly resistant to ______.
|
Clostridium spores are highly resistant to OXYGEN.
|
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Clostridium is catalase positive or negative?
|
Clostridium is catalase negative. Thus oxygen in the absence of catalase is toxic because it spontaneously forms hydrogen peroxide.
|
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Clostridium is superoxide dismutase positive or negative?
|
Negative. Thus Clostridium is very sensitive to superoxide.
|
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Clostridial diseases involve imporant _______.
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TOXINS.
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What are the two main groups of toxins of Clostridium?
|
1. Neurotoxins (tetanus toxin, botulinum toxin)
2. Tissue-damaging toxins (alpha-toxin of C. perfringens, colon-ulcerating toxins of C. difficile.) |
|
What is something interesting about bacteria and "Bostulism"?
The exception to this is in what population/what situation? |
There are no live clostridium bacteria present when the disease is taking place!
The exception to this is found in infants and in wounds. |
|
Honey is the common source of the spores of this bacteria.
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C. botulinum.
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What is a natural source of C. botulinum spores?
|
Honey
|
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What exactly causes botulism?
|
Toxins in food. No live bacteria present.
|
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What is the action of botulism toxin?
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Inhibits nerve conduction at the cholinergic synapses of the peripheral nervous system ---> causing flaccid paralysis ---> paralysis of respiratory muscles, glottis --> airway obstruction.
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What does "botulus" mean? What does clostridium look like? Originally recognized because of outbreak in what food?
|
Botulus = "sausage"
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C. botulinum: invasive capability.
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Not invasive.
|
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Types of C. botulinum?
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Seven, A-G
A, B, E most common in humans. |
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Lethal dose of botulism toxin?
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Very very low (80 ng/kg)
|
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Botulism toxin is carried by a ________.
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Botulism toxin is carried by a BACTERIOPHAGE.
|
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Action of botulinal neurotoxin? (lots of steps)
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1. Synthesized as a single protein that is then cleaved into A and B subunits that remain linked by disulfide bridgess.
2. Not affected by acid in the stomach. 3. Absorbed into bloodstream. 4. B subunit binds to glycolipid receptor on neurons. 5. The A subunit (a zinc-dependent protease) enters the cell and moves into the synaptic vesicles of peripheral nerves. 6. There it inactivates synaptobrevin and block release of acetylcholine and other neurotransmitters. |
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C. botulinum:
facultative/obligate aerobe/anerobe? |
C. botulinum: obligate anaerobe.
|
|
What types of foods are usually involved in botulism?
(extra credit) What types of foods are less likely to be involved? |
Canned foods, improperly heated foods.
Acid foods are less likely to be involved. |
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Doing what makes food safe from botulism toxin? Why?
|
Heating for 10 min at 80 C.
This inactivates the toxin. |
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What is the incubation period of C. botulinum?
|
Usually 12-48 hours.
|
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What is the most common form of botulism diagnosed?
What is is due to? |
Infant botulism. Usually around 10 weeks old.
Honey. Up to 30 spores/100g of honey! |
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B. anthracis is primarily a disease of what types of organisms?
|
Primarily grazing animals.
|
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Two major toxins of B. anthracis.
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1. Edema factor
2. Lethal factor. |
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Edema factor is what?
|
An adenylate cyclase found in B. anthracis. cAMP up. Loss of ion control. Loss of chemotaxis.
Similar to that of B. pertussis |
|
Target of lethal factor.
|
MAP kinase kinases
|
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Notable about B anthracis in human tissue.
|
Massive amounts of bacteria.
|
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Most cases of B. anthracis are what type?
|
Cutaneous. Eschar (dark scab) forms.
|
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Anthrax chest x-Ray
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Mediastial lymph nodes enlarged. Widened mediastinum.
|
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Blood smear of anthracis.
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Gram positive bacillus on UNSPUN smear.
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Does person-to-person transmission of anthrax occur?
|
No.
|
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Life cycle of anthrax?
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Spores in soil --> animal eats --> reproduces in animal --> animal dies --> bacteria take advantage of anaerobic environment --> spores return to soil
|
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Shigella, salmonella, E. coli are what types of bacteria?
|
Gram negative, facultative anaerobes
accessory genes encode virulence, but basic frame is the same the enterics |
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Systemic toxic effect of infection with enterics/Shigella.
|
Hemolytic uremic syndrome
|
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What is one of the main differences between Shigella and E. coli?
|
Almost exactly like E. coli but does not ferment lactose.
|
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Shigella, how many types?
|
Four. Sonnnei, flexneri, boydii, dysenteriae
|
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Which type of shigella is the most virulent?
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S. dysenteriae
|
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What is the most infectious bacterial diarrhea?
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E. coli
|
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Most important mode of transmission of Shigella?
|
Person-to-person
|
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Salmonella requires how much of a dose?
|
A large dose
|
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Shigella requires how much of a dose?
|
Very low dose, about 50 bacteria. High secondary infection rate.
|
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Shigella: invasive?
|
No, tend to be limited to GI, usually self limiting
|
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Shigella: gets into macrophage and does what?
|
Apoptosis, inflammation induced, keeps infection local, leukocytes inherent stool, so is an inflammatory diarrhea
|
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Listeria: inflammation?
|
Little, because doesn't apoptose macrophages
|
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What does shigella use to move around?
|
Actin in macrophages
|
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Why is S. dysenteriae especially severe?
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High levels of shiga toxin.
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Most abundant facultative anaerobe in the gut.
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E. coli (but is far outnumbered by strict anaerobes)
|
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S. dysenteriae is similar to what type. Of E. coli?
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EHEC
|
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S. sonnei is like what type of E. coli?
|
EIEC
|
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Basics of Yersinia
|
Gram negative facultative anaerobes
|
|
Three species of yersinia
|
Y. enterocolitica
Y. psuedotuberculosis Y. pestis |
|
What distinguises Y. pestis from other types?
|
Vector borne
|
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Y. enterolitica signs. What can this be mistaken for?
|
Often right sided abdominal pain. May be mistaken as appendicitis.
|
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Y. enterolitica: symptoms
|
Reactive arthritis
septicemia |
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Risk factors for septicemia with yersinia enterolitica
|
Diabetes
Cirrhosis Hemochromatosis (important - excess iron in blood, note that an important part of host immune system is to deplete bacteria of iron) Graves disease |
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What happens to ferritin activity during fever? Why?
|
Activity goes up --> tries to deprive bacteria of iron.
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Y. enterolitica transmission
|
Pig feces
|
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Y. pseudotuberculosis
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Nodules in the lung. Millet seed nodules.
|
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Y. pestis: a molecular geneticist died while working with this, why?
|
He had hemochromatosis
|
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Where does most plague occur in the US?
|
Arizona and New Mexico
|
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Y. pestis is primarily vector based, but also has another means of transmission
|
Inhalation
|
|
Bacterial agents of greatest concern
|
1. Anthrax
2. Yersinia pestis (droplet, actually requires fairly close contact) 3. Francisella tularensis (Tularemia) 4. Botulism toxin |
|
Lawnmower tularemia
|
Rabbit died and run over with lawnmower. Freq seen in marthas vineyard
|
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Tularemia Vector
|
Ticks
|
|
Y. pestis is a specialist at
|
Becoming systemic. Bacteremia specialist.
|
|
Low subcutaneous dose produces fatal systemic infection in many mammilian species.
|
Y. pestis
|
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Key to high virulence of Y. pestis is
|
Ability to avoid innate immune response (similar to anthrax). Likely induction of sepsis
|
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Plague signs
|
1. Bubo ( huge lymph nodes)
2. Purpuritic lesions 3. Necrotic digits. (why it's called black death) |
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Y. pestis: chest X-Ray
|
See what looks like pneumonia
|
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Primary pneumonic plague
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Must treat immediately
|
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Highest place of plague infection?
|
Madagascar!
|
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Natural carriers of plague in the US?
|
Rodents in the desert
|
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What does Y. pestis do to fleas?
|
Blocks the proventriculus so that fleas can't eat --> always hungry --> bite more --> can't swallow --> vomits and spreads
|
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How does Y. pestis evade the innate immune system?
|
1. Uses a type III system (injectosome needle) that allows direct movement of proteins from bacteria into cells without exposure to the extracellular environment.
2. Very complement resistant 3. Lipids of Yersinia evade TLR4 4. Have mechanisms for acquiring iron. |
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What mechanism is especially important in helping the innate immune system to respond to gram negative bacteria?
|
TLR 4
|
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Y. pestis lipid A
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Evades TLR4. Evidence that inhibiting innate immune response is very important to pestis pathogenesis.
|
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Most commonly used adjuvant is what?
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Alum (actually a lousy adjuvant), have to be careful because of reactions that adjuvant can cause.
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What is the basis of "endotoxins is your friend"?
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Endotoxins activate TRL4
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Basic role of Innate immunity.
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Role of innate immunity is to keep you alive long enough to develop adaptive immunity.
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What is another word for "obligate"?
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"strict"
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Encounter and transmission of C. tetani?
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Spores in soil enter through wound.
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C. tetani: spread.
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Bacteria remain localized while surrounding tissue remains healthy.
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What is the most important toxin made by C. tetani?
|
tetanospasmin.
|
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What is the target of tetanospasmin?
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Inhibitory neurons descending from the brain stem.
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Neuromuscular effects of tetanospasmin?
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Prevents release of inhibitors (e.g. GABA) from inbitory neurons ---> prolonged rigid contraction.
|
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Oxygen profile of C. tetani?
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Strict anaerobe
|
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General properties of C. tetani?
|
Thin gram + rod
Strict anaerobe Spore former Motile Non-invasive |
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Is C. tetani motile?
|
yes
|
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Is C. tetani a spore-former?
|
yes
|
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Tetanospasmin is closely related to what other toxin?
|
Botulism toxin.
|
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What is the main difference between botulism toxin and tetanospasmin?
|
Tetanospasmin uses the axon transport system to move up motor neurons into the CNS.
Botulism toxin affects peripheral nerves. |
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What are some things that can encourage growth of C. tetani?
|
C. tetani is a strict anerobe, so having facultative anaerobes around to eat up the oxygen helps it grow.
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What is the condition of not being able to open the jaw called?
|
Trismus (lockjaw).
|
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Common sign of tetanus other than trismus.
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Stimuli that normally produces a minor reflex (hand clap) may initiate painful spasm.
|
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(extra credit) What is extreme contraction of back muscles called?
|
opisthotonus
|
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(extra credit) Trismus + spasm of facial muscles = ?
|
Risus sardonicus
|
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Tetanus treatment?
|
Antitoxin
Avoid stimulation Maintain airway |
|
Tetanus vaccine.
|
Component of DPT
Requires booster at 10 years. |
|
General properties of C. perfringens
|
Gram + rod
Spore former Obligate anaerobe (but relatively aerotolerant) Highly invasive Grows very fast Copious gas production Non-motile HAS A CAPSULE |
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What is the only Clostridia species with a capsule?
|
C. perfringens.
|
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Apart from gas gangrene, what is another common presentation of C. prefringens?
|
Food poisoning
|
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C. perfringens: how many types and how many toxins?
|
Six types (A-F)
12 toxins |
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C. perfringens: most important toxin?
|
alpha-toxin.
|
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What is the action of alpha-toxin in C. perfringens?
|
Alpha-toxin is a phospholipase that hydrolyzes lecithin and sphingomyelin and lead to cell lysis
|
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What bacteria has theta toxin? What is the action of theta-toxin?
|
C. perfringens. Theta toxin is a pore-forming toxin that causes cell lysis.
|
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What is theta-toxin related to?
|
Streptolysin-O.
|
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C. perfringens: infections (3)
|
1. Gas gangrene
2. Anaerobic cellulitis 3. Food poisoning |
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Gas gangrene: predisposing factors.
|
1. Penetrating wound or trauma.
2. Surgery (esp. of intestine or billiary tract) 3. Abortion or unsantitary childbirth. 4. Burns 5. Cancers (esp colonic/pelvic) 6. Neutropenia |
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Gas gangrene: treatment
|
Surgical debridment, ABX, no antitoxin.
|
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C. perfringens: anaerobic cellulitis
|
Much less severe than gas gangrene
Copious gas Much less localized pain than with gas gangrene. |
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C. perfringens: food poisoning
|
Third most common cause of food poisoning
Contaminated meat most common source Requires a large dose Watery diarrhea, cramps Self-limiting, recovery in 24 hours. |
|
C. perfringens: food poisoning source
|
Contaminated meat
|
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20-30% cases of antibiotic-associated diarrhea, 50-75% of antibiotic associated colitis, and >90% of antibiotic associated pseudomembranous colitis is caused by what?
|
C. difficile
|
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What is the leading cause of community-aqcuired and nosocomial diarrhea in the developed world?
|
C. difficile
|
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How do antibiotics cause the overgrowth of C. difficile? What antibiotics can cause this?
|
Kill normal flora --> competition down --> C. difficile up --> toxins up
Clindamycin Cephalosporins Penicillins |
|
Do outpatients on antibiotic therapy develop C. difficile?
|
Not usually. C. difficile is associated with a hospital setting.
|
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Molecular mechanism of C. difficile toxins
|
Glycosylate Rho proteins, disrupting cytoskeletal integrity and cell signalling.
|
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What are the two toxins of C. difficile?
|
Toxin A and toxin B
|
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What is the action of toxin A in C. difficile?
|
Toxin A damages enterocytes, releasing fluid, causing inflammation.
Has chemoattractant activity, further contributing to inflammatory damage. |
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What is the action of toxin B in C. difficile?
|
Similar to toxin A, but 10 times more potent
|
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What are the "pseudomembranes" in pseudomembranous colitis comprised of?
|
fibrin, mucin, neutrophils, and cellular debris.
|
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C. difficile: detection
|
Cytotoxin assay of stool
Enzyme immunoassay (EIA) (less expensive and more convenient, but less reliable) |
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C. difficile: treatment
|
Discontinue offending ABX
Give oral vancomycin, metronidazole. |
|
Only known reservoir of Corynebacterium diptheria?
|
Human throat.
|
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Assymptomatic carriers in C. diptheria? Demographics?
|
yes, common, esp in children.
|
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C. diptheria: transmission
|
Contact with oral secretions
|
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C. diptheria, invasive?
|
no
|
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C. diptheria: local effects
|
May cause pseudomembranes in pharyngeal epithelium
Local edema |
|
General properties of Corynebacterium diptheria
|
Gram + rod
Non-spore forming Facultative anaerobe Non-motile Non-invasive This was the first bacterial disease known to be caused entirely by a toxin. |
|
Where are the genes for diptheria toxin located?
|
On a certain bacteriophage. Strains without phage do not cause the systemic effects of diptheria.
|
|
Diptheria toxin is what type of toxin?
|
A-B model toxin.
Synthesized as a single polypeptide, cleaved to yield A and B subunits. B attaches and A is inserted into cell. |
|
What is the molecular action of diptheria toxin?
|
ADP-ribosylation of elongation factor 2 (EF2) --> blocks protein synthesis
This is similar to exotoxin A of Pseudomonas aeruginosa. |
|
C. diptheria: presentation
|
Pharyngitis, tonsilitis
Fever, malaise, sore throat Pseudomembranes in throat "Bull neck" appearance of throat |
|
C. diptheria: presentation of neck, cause.
|
"Bull neck" appearance
Due to cervical edema and lymphadenitis |
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C. diptheria: damage to what tissue is the most serious?
|
Heart tissue. Damage is usually not reversible.
|
|
C. diptheria: vaccine
|
Toxoid is a component of DTaP (Diptheria, Tetanus, acellular Pertussis)
Toxin treated with formalin. |
|
What test is used to detect Mycoplasma pneumoniae?
|
Mycoplasma antibody titer
|
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Mycobacteria infection: most notable symptom
|
Cough, headache
|
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Leading cause of "atypical pneumonia"?
|
Mycoplasma pneumoniae
|
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What is the definition of atypical pneumonia? (3)
|
1. Not responsive to sulfonamides or penicillins
2. CXR shows nonlobar, patchy, interstitial pattern 3. No causative agent shown by gram stain or culture. |
|
Does pneumococcal pneumonia cause walking pneumonia?
|
No, pts get sick
|
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Most common cause of "walking pneumonia"?
|
Mycoplasma pneumoniae.
Patients don't get terribly sick |
|
(extra credit)
Two other strains of Mycoplasma? |
Mycoplasma hominus
Ureaplasma ureolyticum Cause GU infections after sexual and verticle transmission. |
|
General properties of Mycoplasma
|
Smallest organism capable of growth on cell-free media
Lacks a murein cell wall, so therefore can assume many shapes. Unaffected by cell-wall ABX Membranes contain sterols, which are obtained from the medum |
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Mycoplasma: only known reservoir?
|
Infected humans
|
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Mycoplasma: spread?
|
Spread by coughing --> respiratory droplets
|
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Mycoplasma: attachment
|
Attaches to respiratory epithelium via adhesive protein (P1) that binds to a sialylated glycoprotein on the host cell.
|
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Mycoplasma: characteristic of growth
|
Slow growing
|
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Mycoplasma: invasive properties
|
Not invasive, usually remains confined to the URT
|
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Mycoplasma: can cause what?
|
Tracheobronchitis
Pneumonia |
|
Mycoplasma: involvement of the alveoli?
|
No
|
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Mycoplasma blocks ______ action.
|
Mycoplasma blocks CILIARY action.
|
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Mycoplasma: treatment
|
Not affected by cell wall ABX
Tetracycline Erythromycin Azithromycin |
|
(extra credit)
Incidence of Legionella pneumophila has increased due to what? |
Installation of central air conditioning!
|
|
L. pneumophila: general course (detailed)
|
Incubation period of 2-10 d. Starts off nonspecifically (fever, malaise, myalgia, headache). Hear rales early in course. Can see a broad spectrum of illnesses. Often more severe in nosocomial cases, which account for about a quarter of all cases. Fatality rate can approach 50%
|
|
Legionella pneumophila: gram stain, culture.
|
Does not stain well, can only be cultured on specialized medium.
|
|
General properties of Legionella pneumophila
|
Gram - bacillus
Parasitizes protazoa in the environment |
|
L. pneumophila thinks it's parasitizing what when it infects a human cell?
|
It thinks it's infecting a amoeba.
|
|
Is a person infected with L. pneumophilus contagious?
|
No!
|
|
Requires special charcoal containing media for culture
|
Legionella pneumophila
|
|
L. pneumophila: encounter and entry
|
Typically inhaled from aerosol generated from contaminated water systems, air conditioning units
Relatively resistant to heat |
|
L. pneumophila: killed by ______ but not by _____?
|
Killed by PMNs, but not by MACROPHAGES
|
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L. pneumophila: grows to large numbers within what?
|
Macrophages
|
|
How does L. pneumophila get its way into macrophages?
|
C3 binds to L. pneumophila --> phagocytosed by macrophages
|
|
What is the definition of typical pneumoniae?
|
Acute onset
Fever Lobar involvement Responsive to antibiotics |
|
Why does mycobacterium often contaminate cultures?
|
Has no cell wall, so is flexible and often escapes attempts to filter.
|
|
S. pneumoniae vs. M. pneumoniae: immune reponse and septicemia.
|
S. pneumoniae: lots of PMNs. Septicemia.
M. pneumoniae: mononuclear infiltrate, thus don't see fever chills so much. Don't see septicemia. |
|
L. pneumophila: risk factors.
|
Age
Cigarette smoking Chronic lung disease Immunosuppression |
|
What is unique about the way that L. pneumophila is taken up?
|
Coiling phagocytosis
|
|
How does L. pneumophila get into macrophages?
|
Coats itself with C3 ---> phagocytosed
|
|
L pneumophila: location of replication
|
1. Coated with C3 and taken up into macrophages.
2. Bacteria modifies phagosome --> phagosomes don't immediately acidify or fuse with lysosomes. 3. As the bacteria multiply in the phagosome, the phagosome exterior becomes associated with smooth vesicles, mitochondria, and rough ER. |
|
Exponential phase bacteria are _______.
Post-exponential phase bacteria are ________. |
Exponential phase bacteria are NONVIRULENT.
Post-exponential phase bacteria are VIRULENT. |
|
What causes switch to virulent L. pneumoniae?
|
Amino acid starvation.
When amino acids become scarce, intracellular bacteria express traits that facilitate escape from the depleted cell. |
|
L. pneumophila: damage due to?
|
Maintly due to host inflammatory response.
|
|
L. pneumophila: treatment
|
Need to activate macrophages enough to kill bacteria
Need to downregulate iron uptake so there is not as much iron in macrophages. Activated macrophages down regulate the transferrin receptor. ABX |
|
Undulant fever
|
Brucellosis
|
|
VirB type IV system
|
Brucella
|
|
Brucella: manifestations
|
Arthritis
Epididymitis Orchitis |
|
Brucella: types
|
1. B. abortus
2. B. Suis 3. B. melitensis (goats) 4. B. canis (dogs, not as important) |
|
Brucella: exposure
|
Exposure to animals (skin, mucous membranes)
Exposure to unpasturized dairy products |
|
Brucella: grow in what?
|
Macrophages
|
|
Brucella: grows associated with what?
|
ER vaculoles. Maturation of vaculoes requires VirB type IV secretion.
Encodes a VirB type IV secretion system. |
|
Brucella: spreads to?
|
Regional lymph nodes
Spread throughout the body, often via the recticuloendothelial system. |
|
Brucella: diagnosis
|
Serology by agglutination.
Isolation and growth of the organism is difficult because it grows so slowly. |
|
Brucella: treatment
|
Treatment with multiple drugs
Similar to treatment of M. pneumoniae. |
|
General properties of chlamydiae, rickettsiae, coxiella, erlichia, and anaplasma
|
Degenerate
Highly specialized Gram-negative Only grow in eukaryotic cells Have lost many of their biosynthetic pathways Have small genomes |
|
Chlamydia: infect what tissues, transmission.
|
Generally cause infections of epithelial tissues and are transmitted by sexual contact or via aerosols.
|
|
Rickettsiae: colonize what tissue, transmission?
|
Colonize endothelia of the circulatory system, and depend on arthropod vectors for transmission.
|
|
Erlichia and anaplasma: colonization, transmission?
|
Are transmitted by ticks and colonize leukocytes (Erlichia = monocytes, Anaplasma = granulocytes)
|
|
Three major clamydial species
|
1. C. pneumonia
2. C. trachomatis 3. C. psittici |
|
C. trachomatis
|
Common cause of blindness in developing world
|
|
C. psittici: encounter, transmission
|
Seen with handling of birds
|
|
Elementary bodies
|
Chlamydia
|
|
What is the infectious form of chlamydia?
|
Elementary body
|
|
What is the metabolically active form of chlamydia?
|
Reticulate bodies
|
|
What makes the reticular bodies convert back to elementary bodies?
|
Depletion of nutrients
|
|
Chlamydia-filled vesicles are called what by pathologists?
|
Inclusion bodies
|
|
What causes the transmission of ocular chlamydia?
|
Ocular secretion-seeking flies
|
|
Chlamydia trachomatis: most important disease?
|
Pelvic inflammatory disease.
Most cases are polymicrobial Treat for both if you find one. |
|
PID: sequelae
|
Ectopic pregnancy
Infertility Chronic pelvis pain |
|
Coxiella burnetii: characteristics
|
Highly infectious spore like elementary body
Seen in agricultural workers working with animals giving birth. Reaches very high concentrations in placenta. Has been used for nonlethal bioweapons Extremely infectious |
|
Coxiella burnetii: characteristic fever
|
Q fever
|
|
Coxiella burnetti: manifestations
|
Range of illnesses
mild flu <---> pneumonia <---> chronic fever with deep tissue infection. Feel lousy but usally recover |
|
Rocky Mountain Spotted Fever: vector
|
Not particular about its vector - has been known to be carried by mosquitoes
|
|
Tick-borne diseases: general manifestations
|
All associated with thrombocytopenia (because of a lot of bacteria in blood)
Transaminase levels elevated |
|
Tick-borne diseases: most severe form
|
Rocky Mountain Spotted Fever
|
|
Rocky Mountain Spotted Fever: mortality
|
20% mortality if untreated. 5-10% treated.
|
|
Petechiae = damage to what?
|
Damage to microcirculation.
|
|
Antibiotics that will kill intracellular pathogens
|
Tetracycline, doxycycline
|
|
Rickettsiae: treatment
|
Oral tetracycline or doxycycline
More severe cases require IV ABX |
|
RMSF: long term sequelae
|
Paralysis of lower extremities
Gangrene Hearing loss Blindness Loss of bowel or bladder control Movement/speech disorders |
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RMSF: risk factors
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Age, male sex, African descent, alcohol abuse, G6PD deficiency
|
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RMSF: geographic distribution
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Southeast USA
|
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R. Rickettsia: stains, smears
|
Not seen on blood smear, doesn't stain with conventional stains.
|
|
Erlichia and anaplasma: blood smear, stains?
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Only occasionally seen on blood smear or using conventional stains.
|
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TBRD = ?
|
Tick-Borne Rickettsial Diseases
|
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When Legionella pneumophila infects a phagosome, are the phagosomes not containing bacteria affected?
|
No. Only the phagosomes containing Legionella are affected.
|
|
What types of vesicles does L. pneumophila "hijack"? How?
|
Vesicles derived from the ER in transit to the Gogli apparatus.
This is thought to happen via L. pneumophila controlling a small G protein that controls ER to Golgi trafficking. |
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What type of system does L. pnuemophila use to modify a phagosome?
|
A type IV secretion system.
|
|
What are the genes that encode the type IV secretion system in L. pneumophila called?
|
"dot" genes (Defect in Organelle Trafficking)
|
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Basic characteristics of brucella
|
Pleomorphic gram - rod
Urease-producing Facultative intracellular |
|
What general type of disease does brucellosis cause?
|
Granulomatous
|
|
Where do obligate intracellular pathogens get ATP?
|
From the host.
|
|
How many cases of C. trachomatis are there in the US annually?
|
3,000,000!
|
|
Recently, research has shown that C. pneumoniae has been shown to be associated with what?
|
atherosclerosis
|
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C. pneumoniae: manifestations
|
Pharyngitis
Bronchitis Atypical pneumonia |
|
C. burnetti: where does it live?
|
C. burnetti is adapted to live within professional phagocytes.
Enters cell by phagocytosis and the phagosome fuses with the lysosome. C. burnetti becomes metabolically active only at the low pH in these vesicles. |
|
What does chronic Q fever usually lead to?
|
To endocarditis
|
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Are rashes common in Rickettsiae? In Coxiella burnetti?
|
Common in Rickettsiae, uncommon in C. burnetti (Q fever does not cause a rash)
|
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Are Chlamyidal elementary bodies infectious? What about residual bodies?
|
Elementary bodies are infectious, residual bodies are not.
|
|
(extra credit)
Chlamydia: invasive disease |
C. trachomatis
Lymphogranuloma venerium, an infection of the genital tract results in rapid invasion and development of systemic infection. Seen in gay men and prosititutes. Genital or anal fistulae, etc. C. pneumoniae In atherosclerotic lesions. |
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Chlamydia accompanies ________ in 45% of cases.
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Chlamydia accompanies GONORRHEA in 45% of cases.
|
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Chlamydia: attributes of acute infection in women
|
Urinary pain and frequency
Vaginal discharge Pelvic pain (cervicitis) |
|
Chlamydia: attributes of acute infection in men.
|
Non-gonococcal urethritis (thin, watery, penile discharge with pain on urination)
Prostatitis Epididymitis Proctitis |
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Chlamydia: manifestations of vertical transmission
|
Conjunctivitis
Mild pneumonia Present at 3-6 weeks of life |
|
Chlamydia: diagnosis
|
Clinical evidence or
Direct Fluorescent Anitbody (DFA) Test |
|
Chlamydia: treatment
|
Doxycycline or erythromycin.
Azithromycin (long half-life) is effective at eradicating C. trachomatis in one 1 g dose. |
|
(extra credit)
Cytoplasmic vesicles containing Erlichia or Anaplasma are called what? |
Morulae
|
|
Rickettsiae: multiplication and spread similar to what other bacteria?
|
Similar to Shigella-Listeria.
|
|
What is a commonly used test for TB?
|
the Mantoux test
|
|
Basic characteristics of Mycobacterium tuberculosis
|
Aerobic, slow-growing rod
Has a waxy coat so doesn't gram stain Can use an acid-fast stain instead. |
|
What are the typical members of the "M. tuberculosis complex"?
|
M. tuberculosis
M. africanum (almost identical to M. tuberculosis) M. bovis (ingestion of raw milk, close contact with cattle) |
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M. tuberculosis: transmission
|
Respiratory droplets
|
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M. tuberculosis is resistant to ______.
|
M. tuberculosis is resistant to DRYING. (because of its waxy coat)
|
|
How contagious is TB?
|
A. Brief encounters pose little risk.
B. ID <10 bacilli. Masks worn when active TB patients are hospitalized. Household contacts have 50% risk of infection if "AFB" (acid-fast bacilli) can be observed in the sputum Close contacts have only 5% risk if bacilli can only be detected by culture of sputum. |
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What does it mean if a TB patient is "smear positive"?
|
It means that acid-fast bacilli (AFB) can be observed in the sputum.
|
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M. tuberculosis: entry
|
Inhalation of respiratory droplets --> alveoli --> bacilli ingested by macrophages
|
|
What does M. tuberculosis do to survive within macrophages?
|
It arrests the normal maturation of the phagosome. As a result, the phagosome resembles an early endosome.
pH is neutral and phagolysosomal fusion is greatly diminished. |
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M. tuberculosis: initial spread
|
MTB might travel in macrophages via blood and lymph to any area of the body.
|
|
Where is TB seen most in the lungs?
|
In the upper lobes where oxygenation is better.
|
|
What are the three characteristics of M. tuberculosis that influence pathogenesis?
|
1. Slow growth.
2. Presence of a lipid-rich cell envelope. 3. Expression of a specialized protein secretion system. 4. The ability to eat host membranes |
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M. tuberculosis: growth
|
Slow. Doubles every 24 hours under optimal conditions.
|
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M. tuberculosis: cell envelope
|
Covered by a thick layer of wax. Wax layer has porin channels that hydrophilic molecules pass through.
This wall a. protects from most environmental insults b. limits effectiveness of immune system c. limits effectiveness of ABX |
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What is the name and strain of a bacteria used to vaccinate people from TB?
|
the BCG (Bacille Calmette Geurin) attenuated strain of M. bovis.
|
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The BCG vaccine is effective at preventing ____ _____ but not _________.
|
The BCG vaccine is effective at preventing TB MENINGITIS IN YOUNG CHILDREN but not INFECTION.
|
|
How did the BCG strain become avirulent?
|
Grew on potato slices for years and eventually had an RD1 deletion that is responsible for the lost of TB's protein secretion system.
|
|
M. tuberculosis: aquiring nutrients
|
M. tuberculosis deals with this problem by having an unusual ability to extract and digest cholesterol from the membranes that surround it.
|
|
What percentage of immunocompetent individuals will control M. tuberculosis infection and remain asymptomatic?
|
~90%
|
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Individuals "latently infected" with M. tuberculosis have what percentage risk of "reactivation disease"?
|
~5%
|
|
What promotes reactivation of M. tuberculosis?
|
Immunosuppressive states (HIV, steroids, TNF antagonists)
|
|
What is disseminated TB with a distinct lack of host immunity called?
|
"Milliary" TB
|
|
What percent of immunocompetent individuals will have primary progressive TB?
|
~10%
|
|
What is the leading cause of death in HIV patients?
|
TB
|
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The body often walls off M. tuberculosis in what structures?
|
Granulomas
|
|
Caseous necrosis
|
TB
"incomplete necrosis" |
|
What are the antibiotics given for TB, and what is the time course?
|
Isoniazid, rifampin, pyrazinamide, and ethambutol.
Taken for 9 months. |
|
What is DOT therapy?
|
Direct Observed Therapy
|
|
What is the drug of choice for latent TB?
|
Isoniazid (INH)
|
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What is "cavitation"?
|
Cavitation is the liquification and rupture of a caseous lesion, causing a spread of bacteria to other sites.
|
|
What are three bad consequences of TB cavitation?
|
1. Growth: MTB is aerobic, by breaking containment it can get more oxygen and can grow to enormous titers.
2. Contagion: cavitation promotes spread of infection 3. Spread: bacteria spreads to other sites around the body |
|
M. tuberculosis: damage
|
Mainly due to the immune response.
|
|
What are two systemic effects of IL-1 and TNF?
|
Fever and weight loss (among others)
|
|
M. tuberculosis: diagnosis
|
AFB staining: Fast but insensitive.
Culture: slow but definitive. Can use "Bactec" instrument and selective media to speed growth. TST (PPD) Test: Asks the question, "Has this person been exposed to the anitgen?" |
|
Is the PPD test helpful in someone who has been vaccinated with BCG?
|
Yes! But only if the vaccination was administered at least five years ago.
|
|
What is the most likely reason to get a falsely positive PPD in the US?
|
A cross-reaction with an atypical mycobacteria.
|
|
False negative PPDs may be due to what in patients?
|
Anergy, the inability to mount an immune response. Immunocompromised patients.
|
|
What new tests are available that can tell the difference between MTB and BCG?
|
T-Tube TB and Quantiferon
(Interferon gamma release assays) |
|
In TB, what is bacterial resistance due to?
|
to selecting for spontaneously resistant mutants.
Mycobacteria do NOT transfer antibiotic resistance determinants via horizontal transfer. |
|
What is the criteria for a positive TST (PPD) test in a child - US born with no special risk?
|
> or = to 15 mm
|
|
1/3 of the world's population is infected with this bacteria.
|
M. tuberculosis
|
|
General properties of spirochetes.
|
Corkscrew shapes
Thin - need DARKFIELD MIRCOSCOPY to see them Possess inner and outer membranes like gram negatives, but they are not conventional gram negatives. Don't gram stain well Have ENDOFLAGELLA and are highly motile. Due to their motility, they cause systemic infection. Difficult/impossible to grow in vitro. |
|
What is Darkfield microscopy commonly used to visualize?
|
Spirochetes
|
|
Do B. burgdorferi and T. pallidum have LPS?
|
No
|
|
Name of bacteria : disease
Treponema pallidum : ? |
Syphilis
|
|
Name of bacteria : disease
Borrelia burgdorferi : ? |
Lyme disease
|
|
Name of bacteria : disease
Several Borrelis sp. : ? |
Relapsing fever
|
|
Name of bacteria : disease
Leptospira interrogans : ? |
Leptospirosis
|
|
Disease : Name of bacteria
Syphilis : ? |
Treponema pallidum
|
|
Disease : Name of bacteria
Lyme disease : ? |
Borrelia burgdorferi
|
|
Disease : Name of bacteria
Relapsing fever : ? |
Several Borrelia sp.
|
|
Disease : Name of bacteria
Leptospirosis : ? |
Leptospira interrogans
|
|
What are the two major diseases caused by spirochetes in the US?
|
Syphilis
Lyme disease |
|
Lyme disease is acquired from the _____ tick.
|
Lyme disease is acquired from the IXODES tick.
|
|
Larval ticks acquire B. burdorferi from chronically infected ____ _____ _____.
|
Larval ticks acquire B. burdorferi from chronically infected WHITE FOOTED MICE.
|
|
Ixodes ticks are about the size of what?
|
A period at the end of a sentence.
|
|
Erythema migrans
|
Expanding rash seen in Lyme disease.
(Can culture bacteria from the edge of the expanding rash.) |
|
Lyme disease manifestations druing early disseminated infection:
Skin: Heart: Joints: Nervous tissue: |
Lyme disease manifestations:
Skin: secondary erythema migrans Heart: heart block (bacteria "line up" with muscle fibers.) Joints: arthralgia Nervous tissue: shooting pain, paresthesia, Bell's Palsy |
|
Lyme disease: bacterial load
|
Is never high.
|
|
Lyme disease: appearance of infected synovium
|
Almost looks as if it has germinal centers in it.
|
|
Lyme disease: cycle of manifestation of chronic disease
|
Waxing and waning
|
|
Lyme disease: what percenage of untreated patients will develop chronic inflammatory arthritis?
|
About 10% of untreated individuals.
|
|
Lyme disease: what is associated with the risk of developing chronic inflammatory arthritis?
|
The HLA-DR4 haplotype.
|
|
(extra credit)
What haplotype is associated with chronic inflammatory arthritis? |
HLA-DR4
|
|
Does B. burgdorferi stimulate a strong inflammatory response?
|
Yes. Strong response even though there are very few bacteria present.
|
|
(extra credit)
What is a pathology of the skin associated with Lyme disease? (not the rash) |
Acrodermatitis atrophicans
|
|
OspA
|
Outer surface protein A. Produced by B. burgdorferi. Allows bacteria to adhere to tick midgut.
|
|
What is the protein that allows B. burgdorferi to attach to tick midgut?
|
OspA
|
|
What activates dormant spirochetes?
|
The increase in warmth and the "blood" due to tick feeding.
|
|
When B. burgdorferi is "activated," what changes take place on a molecular level? What processes ensue? (long)
|
Feeding --> decrease amount of OspA, allowing release from tick midgut epithelium --> increases production of OspC --> binds plasminogen --> when plasminogen gets activated to plasmin, helps the bacteria penetrate the midgut of the tick --> systemic infection of the tick --> pass through salivary gland --> bind to a protein that will protect the spirochete from complement binding in the mammal --> gets onto mammalian skin and uses multiple pathways for attachment.
|
|
B. burgdorferi travels best in what type of environments?
|
viscous environments.
|
|
What are some problems with trying to target Lyme disease with antibiotic therapy?
|
It presents few neutralizing antigenic targets. Many of the known surface antigens are turned off in tissues.
|
|
VlsE
|
Lyme disease. Highly variable vlsE gene segments result in antigenic variation.
|
|
What toxins does B. burgdorferi have?
|
No known exotoxins. No known endotoxins, even though it has an outer membrane.
|
|
What is responsible for the vigorous immune response associated with B. burgdorferi?
|
Lipoprotein production. Has no endotoxins or exotoxins.
|
|
The prevention of Lyme disease is largely __________.
|
The prevention of Lyme disease is largely BEHAVIORAL.
|
|
How long does it take for a tick to transmit Lyme disease?
|
48 hours - they are slow feeders.
|
|
What are the things that you can do to prevent Lyme disease?
|
Check warm, dark places
Wear light clothing to be able to spot ticks Insect repellant |
|
Lyme disease: OspA vaccine
|
No longer on the market. Not clear how long-lasting immunity was. Interestingly, antibodies against OspA are not effective in the mammilian host, but they are effective when the antibodies are taken up into the tick. Thus this vaccine is basically a vaccine for the ticks!
People needed to get a booster every year. |
|
RPR
|
Test for syphilis
|
|
What is a serious disease caused by a spirochete that can be transmitted vertically?
|
Syphilis (Treponema pallidum). Can cross the placenta and cause a multisystemic infection.
|
|
Syphilis: culture
|
Almost impossible to culture.
|
|
What was the "Great Pox"?
|
Syphilis
|
|
What is the third most common STD?
|
Syphilis! Behind chlamydia and gonorrhea.
|
|
When you see the presence of syphilis, what are you suspicious of?
|
Other STDs
|
|
Syphilis: encounter, transmission
|
Humans are the only known host. Enters mucous membranes or small abrasions in the skin.
|
|
Primary syphilis: timing, hallmark presentations
|
Local infection
Days-weeks after infection. See painless chancres (spontaneously heal in 2-6 weeks) that contain spirochetes, PMNs, then later macrophages and lymphocytes. |
|
Secondary syphilis: timing, symptoms.
|
Invasion and systemic illness
Weeks-months after infection. Flu-like symptoms, generalized lymphadenopathy, (often resolve in weeks-months) |
|
Tertiary syphilis:
|
Chronic infection
Years after infection. See chronic inflammation of bone and soft tissue (Gummas). Vasculitis (esp of thoracic aorta - tree bark appearance), causing dilation, aneurysm. CNS effects. Proprioceptive sensory loss (tabes dorsalis), and personality changes. |
|
What is called the "Great imitator"?
|
Syphilis
|
|
Problems with targeting T. pallidum for therapy.
|
Highly motile
Presents few antigenic targets (outer membrane largely devoid of protein) Some surface proteins are subject to antigenic variation (TprK). (Like VlsE of B. burgdorferi). |
|
TprK
|
Antigenic variation in syphilis
|
|
T. pallidum: toxins
|
No known exo or endotoxins, but produces lipoproteins that induce cytokines.
|
|
Syphilis: treatment
|
Penicillin
|
|
Similarities between Lyme disease and syphilis
|
1. Chronic infections that can be divided into stages.
2. Periods or remission followed by relapse. 3. Low bacterial load. 4. In spite of vigorous immune response, organism is not cleared. |
|
Vibrio cholerae: encounter
|
Contaminated water or food.
|
|
V. cholerae: colonization and multiplication
|
Attaches to and grows on intestinal epithelium, especially the small intestine.
|
|
General properties of V. cholera
|
Gram negative
Comma-shaped Facultatice anaerobe Non-spore former Non-invasive Highly motile Able to replicate at alkaline pH Classic example of disease with all important symptoms due to action of a single toxin. |
|
El tor
|
A hemolytic variant of "classical" Vibrio cholerae. Causes disease in 25-50% of those infected. Endemic to Southeast Asia.
|
|
(extra credit)
O139 |
This is the "Bengal" antigenic variant of El tor V. cholera.
|
|
What effect does the acid of the stomach have on V. cholerae?
|
It kills many of the bacteria, but it also renders the bacteria more infectious. Thus stool infected with V. cholera may be very infectious for a short period.
|
|
How does V. cholera "find" the intestinal epithelium? What bolsters its motility?
|
Via a chemotactic mechanism. Motility is enhanced due to secretion of mucinase.
|
|
V. cholerae: surface appendage that binds to intestinal epithelium.
|
Toxin-coregulated pilus (TCP)
|
|
What does V. cholera do to inhibit the growth of local normal flora?
|
It raises the pH of the local environment
|
|
General characteristics of cholera toxin.
|
A-B model toxin with A1B5 stoichiometry
B subunits form a ring with A at center B binds to a glycoprotein receptor (GM1, a ganglioside) on cells of intestinal epithelium B passes A through center of ring and into cytoplasm of target cell. |
|
What is the target of the A subunit in cholera toxin?
|
A membrane-bound GTPase
|