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231 Cards in this Set
- Front
- Back
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Obligate anaerobes of the human intestine:
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Bacteroides
Clostridum |
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Structure and growth of Clostridum perfringens:
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Obligate Gram POSITIVE bacillus
(much larger than gram negs) may stain gram pos and neg. considered an endospore producer though difficult to demonstrate It is encapsulated an nonmotile |
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Culture and growth of Clostridum perfringens:
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grows rapidly on BAP (doubling time of 10 minutes)
when growing on carbohydrates, it produces a lot of gas (seen in gangrene) gas production in infected tissues = crepitation found in intestinal tract and endospores in water and soil |
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Necrotic disease caused by Clostridum perfringens
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Gas gangrene- endospores found in soils infect traumatic muscle injuries (gunshot, shrapnel, puncture sounds etc)
Severe muscle destruction (myonecrosis). this is life threatening. diseased tissue it cut away and patient is placed in hyperbaric oxygen changer to eliminate the anaerobe |
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What can endometritis be caused by?
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Clostridum perfringens. The non-living material retained in the uterus becomes contaminated. An immediate hysterectomy is required. This disease is less frequent with legalization of abortion.
Also, Chlamydia trachomatis (D-K) |
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Can Clostridum be associated with food poisoning?
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Yes. Clostridum perfringens is ingested in high numbers. 8-24 hours later is nausea, vomiting and abdominal pain and diarrhea. Recovery is within 24 hours.
Associated with meat dishes (stews, soups or gravy) when food is not sored at proper refrigeration. Third most common food poisoning |
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Describe Clostridium tetani as compared to perfringens:
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thin gram positive bacillus but frequently stains gram neg
endospores seen READILY in lab b/c characteristic drumstick appearance HIGHLY motile and may spread like proteus Endospores are found in soil contaminated with feces May be cultured from healthy human intestine without apparent disease obligate anaerobe. Paris hilton was bit by her pet and got a tetanus shot |
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wWhat disease is associated with Clostridium tetani?
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Tetanus!
aka lockjaw caused by contamination of a break in the skin with C. tetanus endospores. Infected tissue has low oxidation reduction potential typically puncture wounds accompanied by tissue necrosis due to production of exotoxin called tetanospasmin (A-B structure) |
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Is clostridum responsible for neurotoxins?
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YES!
Tetanus toxin (TeNT) causes a spastic paralysis of a limb, jaw, Botulinum toxin (serotype A-G) cause flaccid paralysis of a guinea pig. |
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What is the Clostridial tetanus toxin related to? Describe the structure!
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Clost Tet is related to Botulinum Neuro Toxin (BoNT)
Amino-terminal end of these toxins have Zinc-metalloprotease activity which cleave endocytic vesicle membrane proteins found in nerve cells The very C-terminal portion of the neurotoxin contains a domain necessary for binding neuronal cell receptors |
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How does the Tetanus NT work physiologically?
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Toxin becomes disseminated and in the spinal cord, it blocks postsynaptic inhibition of the spinal motor reflexes.
Results in spasmodic contractions of muscles. Incubation time between wound infection and disease ranges from several days to weeks Amount of toxin is very small. Untreated fatality rate is 60% Death by exhaustion and respiratory failure |
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What might you expect if a baby is born with a facial spasm?
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Neonatal tetanus.
Attacks during first days of life. Vaccines with help. evidenced in brazil and china Results from tetanus spores introduced through poor hygiene during childbirth. Contaminated devices used to cut umbilical cord. or using cattle dung to heal umbilical stump |
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How to prevent and treat C. tetanus infection:
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Neutralizing antibody to the toxin.
Treatment uses curare-like drugs that cause counteracting flaccid paralysis are used in severe cases Immunization with tetanus toxid is routine for children. T part of DTaP booster every 10 years active immunization of pregnant women to prevent neonatal disease |
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What is a fatal form of food poisoning brought about by Clostridium botulinum?
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Botulism
Germination of C. botulinum endospores in foods that have not been sufficiently heated |
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Struture/gowth of Clostridum botulinum:
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Gram Positive bacillus
obligate anaerobe relatively fastidious compared to other clost. classified on the basis of antienic type of botulinum toxin (BoNT types A through G). Human pathogens are A B E and the ones encoded on a prophage are C and D Immunization agasint one toxin does NOT protect against other serotypes Species represents at least 4 different distinct metabolic types which may be divided into four different species later |
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How might one acquire botulism?
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Clostridum botulinum is found in soil and in sediment of bodies of freshwater.
Food poisoning event comes about thwne spores germinate in alkaline type foods like beans or mushrooms that are insufficiently heated growth of the organism upon storage in an anaerobic environment of sealed jar/can leads to production of toxin food is consumed without suggestion of spoilage Acidic foods such as canned fruits do NOT support clostridum botulinum |
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What serotypes of Clostridium botulinum cause human disease:
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A B or E
paralysis due to toxin begins a day and a half to four days after ingestion of contaminated food. Paralysis begins with laryneal ocular or respiratory muscles and then progresses to voluntary muscles = flaccid paralysis Local injections of BoNT can provide cosmetic therapies types C and D are encoded by prophages |
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How does the Clostridum botulinum toxin work?
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Toxin blocks transmission of nerve signals at nmj by blocking releae of NT aceytlcholine
Toxin is A-B type. Genetic location differs among types. C and D are antigenic types encoded by prophages. Enterotoxin is heat labile but it is acid resitant and NOT destroyed int he stomach. But germination is prevented by acidic conditions |
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What are the three diseases of Clostridium botulinum?
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-Food Poisoning
-Infant botulism -Wound botulism |
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What happens with Clostridium botulinum in babies?
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Infant Botulism- org colonizes GI tract and there is in vivo production of neurotoxin. Disease begins upon weaning when the flora undergoes changes and don't present competition.
Can cause SIDS associated with sweetening formula with honey that contains spores |
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what treatments are used for Botulism?
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Supportive measures that enable breathing such as mechanical ventilation
Anti-toxin may be useful (but may cause hypersensitivity) Antibiotics are useless b/c it is an exotoxic disease prevent by adequate cooking and avoiding honey |
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What disease is a problem for migratory birds?
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Clostridium botulinum!
Avian botulism kills 10-50k birds a year. Ducks most susceptible death occurs by drowning. |
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What are the characteristics of Clostridium difficile?
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Gram positive
strict anaerobe Recognized as a pathogen only recently. Diarrhea appears upon treatment is routine side effect. but may cause fatal inflammation of colon |
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In general, Clostridium difficile is non-invasive. what does this mean?
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The organism does not go directly through the intestinal wall into blood stream. Rather, it stays in hollow intestinal space and causes damage by producing two toxins (Tox A and ToxB) which attack the intestinal wall
Causes pseudomembranous colitis find toxins in the stool |
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What produces pseudomembranous colitis?
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Clostridium difficile.
visualization of colon by proctoscopy reveals thick pseudomembrane of the colon surface made of fibrin, leukocytes and nectrotic colonic epithelial cells. C. diff can only grow with normal flora wiped out by antibiotic treatment |
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Is Clostridium difficile considered normal flora?
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YES
isolated from intestines of 4% of healthy adults. Cultured in feces of neonates spores are a common contaminant of hospital environment. spores spread on hands of staff |
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How does the Clostridium difficle toxins work?
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ToxA enters epithelial cells causing cytoskeletal protein rearrangements and loss of tight junction between cells
This allows ToxB to enter lamina propria where it and ToxA are cytotoxic. Strong host inflammatory response Ampicillin and clindamycin often irritate the disease mild form of disease will clear upon discontinuation of antibiotics Use vancomycin to eliminate C. diff infection |
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What is the most common gram negative bacillus, obligate anaerobe in the intestine?
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Bacteroides!
most are harmless and commensal. Bacteroides fragilis causes 90% of intraabdominal infections where fecal contamination of peritoneal cavity due to ruptured apendix or intstinal surgery Usually mixed infections with E coli capsule produced by bacteroides |
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What is neat about Bacteroides fragilis?
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Uses a wide rane of dietary polysaccharides and capacity to create variable surface antigens by multiple DNA inversion systems
complex phase switching system allows multiple operons of polysaccharide synthesis and transport capsule |
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Have Koch's postulates been fulfilled for Bacteroides fragilis?
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NO
strains responsible for enterotoxigenic diseases in lambs and children strains produce exotoxin that acts on cultured cells it possibly has pathogenic clones like E coli |
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What are the two major kinds of neisseria?
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N. gonorrhoeae
causes the STI gonorrhea N. meningitidis causes meningitis These are OBLIGATE human pathogens both invade cells but replicate EXTAcellularly |
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What is the cellular morphology of Neisseria?
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Gram NEGATIVE
diplococci "kidney shaped" N. meningitidis is encapsulated NO flagella have twitching motility on solid substrates (mediated by extension and retraction of IV pili) |
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Is Neiserria motile?
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NO flagella
have twitching motility on solid substrates (mediated by extension and retraction of IV pili) |
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What is unique about the Neisseria endotoxin?
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No repeating O-antigen polysaccharide
LOS instead of LPS (kipooligosaccharide) |
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Are Neisseria naturally tansformable?
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Yes! they can take up DNA natually from the environment
aka naturally competent process involves type IV pili this results in great genetic diversity and antigenic variation from the exchange of genetic material between strains |
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How would you grow Neisseria?
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Grown readily overnight on complex media
-Chocolate agar -Thayer-martin agar medium selects for neisseria MUST be incubated at 5% C atmosphere |
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If you did a direct exam on Neisseria infected tissue where would you find the bacteria?
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intracellular inside neutrophils
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How does Neisseria meningitidis cause disease?
(remember, Neisseria is strictly a human pathogen) |
N. meningitidis can colonize the nasopharynx
It can then spread to the blood causing meningococcemia and to the meninges on occasion its polysaccharide capsule blocks phagocytosis and it causes significant vascular damage during systemic infection -damage is due to large amounts of LOS (immune reactive) -LOS is shed from surface in outer membrane blebs (causes vascular damage) |
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Wha happens inf pathogenesis from Neisseria meningitidis is not dx?
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rapidly fatal
near 100% mortality if untreated meningococcemia can occur without meningitis, however. (still fatal) |
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How can you treat Meningococcmeia?
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anti-capsular antibodies to help complement fixation and opsonization
penicillin is the primary treatment |
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Is there such thing as a Neisseria meningitidis vaccine?
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yes.
5 capsular types tetravalent vaccine no vaccine for type B (polysaccharide is composed of polysialic acid, an antigen found in humans) type B causes 45% of cases in US |
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Where is N. meningitidis epidemic?
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50k in Sub-saharan Africa (meningitis belt)
might be associated with the Hajj |
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What is the second most common STI in the US?
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Neisseria gonorrhoeae
(800k cases annually but only 350k are reported) 62M world wide transmitted via sexual contact or to child during birth strictly human |
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who is more sympomatic of gonorrhoeae?
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Men! only 5-10% asymptom
woman are 50-80% asymptom |
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How does a gonorrhoeae infection take place in men?
in women? |
Urethritis > epididymitis > sterility
(may disseminate) women: cervicitis and cystitis > PID > sterility may disseminate may cause Opthalmia neonatorium (newborns) / blindness |
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What can happen in women with gonorrhea?
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PID
this may result in infertility, ectopic pregnancy, and chronic pelvic pain 50-80% of women are asymptomatic (more dangerous) |
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Describe the steps to infection by Niesseria
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1. pilli anchor and attach (tight adherence) on epithelial cells
2. invades epithelium and transcytosis 3. intracellular in monocytes and leukocytes 4. serum resistance with capsule |
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What Mycobacterium infects
birds cows/humans fish cattle |
birds = M. avium
cows/humans = M. bovis fish = M. marinum cattle = M. avium sp. paratuberculosis |
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What are the four human mycobacterium pathogens?
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avium (opportunist in AIDS patients)
leprae tuberculosis bovis |
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What is the cell wall structure of Mycobacterium?
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(technically would be gram pos but they do not gram stain)
The cell wall is composed of peptidoglycan, arabinogalactan, mycolic acid, lipoarabinomannan (in that order) |
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How does one stain a Mycobacterium?
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Acid Fast!
Use Zeihl-Nielsen Stain: Add carbolfuschin stain, heat, dyes becomes imbedded in wall, remove from heat and wash with acid |
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What would a characteristic Acid fast stain for Mycobacterium look like?
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"roping" or "serpentine cords"
bacilli |
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How prevalent is Mycobacterium tuberculosis?
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1/3 to 1/2 of world is infected
2 MILLION deaths per year |
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Tell me about the colony morphology of Mycobacterium tuberculosis:
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Mycobacterial cell wall: unique, waxy
-slow growing, can take a month to form a colony -cultured in vivo under high containment BSL3 -can be studies in animals |
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How does M. TB cause pathogenesis?
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Intracellular pathogen
Prevents phagosome maturation and fusion with the lysosome Formation of granules |
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How can you contract M. TB?
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Aerosol droplettes, must be inhaled and go to lung alveoli
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What type of cells can kill M. TB?
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macrophages activated by T-cells. Attack infected Macrophages and form a granuloma to prvent the spread
turns into latent TB |
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What type of toxins does M TB form?
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Trick question: none
symptoms are caused by host response to bacteria |
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What factors prevent M TB maturation of phagosome and survival within phagosome?
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-cell wall components of Lipoarabinomannin (LAM)
-secreted proteins (ESX-1 system and PknG kinase) -Iron acquisition by mycobactins and exochelins |
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What are the three stages of M TB disease?
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1. Infection:
active replication, presents with symptoms of respiratory illness 2. Latency/Chronic Phase: very low numbers of M TB, no symptoms, not contangious 3. Reactivation / Active Phase: MTB increases in number, host immune response causes symptoms |
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What are the signs of active M TB infection?
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coughing
tiredness fever chest pain coughing blood weight loss |
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What ways can you detect M TB infection?
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skin test
lung x-ray culturing sputum smears blood test |
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What is the BCG vaccine?
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Bacilllus Calmette-Guerin is comprised of attenuated strain of Mycobacterium bovis
It is a LIVE vaccine so cannot be given to AIDS patients |
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What does a PPD skin test measure?
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hypersensitivity to a protein derivative of Mtb
Positive test (induration and erythema) by 3 days indicates immune memory this can be due to infection in the past by any mycobacterium Must perform true diagnosis of M TB by culturing |
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How is Mycobacterium TB treated?
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FIRST LINE
-Isoniazid (INH) = mycolic acid synthesis inhibitor -Ethambuton = inhibits arabinoglatan synthesis -Pyranzinammine = inhibits fatty acid synthesis -Rifampiin = inhibits RNA polymerase Is Every Penis Raging? Maybe, All Fornication is Raunchy SECOND LINE -Ciprofloxacin (fluoroquinolone- DNA girase) -Moxiflocaxin (fluoroquinolone) -Amikasin (aminoglycosine- protein synthesis) cock movement assures genital fun probably |
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What is does it mean for Mycobacterium TB to be MDR and XDR
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MDR = Multi Drug Resistant (INH and Rifapmicin)
XDR = Extensively Drug Resistant (INH, Rifampicin, fluoroquinolone, and at least one other second line) |
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What is significant about Tugela Ferry?
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Had 52 individuals that are XDR TB with AIDS
median death was in 16 days yikes |
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What is the main reservoir of M. TB?
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Humans
The majority of those infected do NOT develop disease Only those with disease can transmit the infection |
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What causes Hansen's Disease?
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Hansen's Disease = Leprosy
Mycobacterium leprae Spread person to person |
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Can you grow M. leprae in culture?
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No.
slowest growing bacterium known, doubling time of 14-16 days Armadillos |
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What are the two forms of Leprosy?
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Tuberculoid:
(paucibacillary) Strong cellular immune response, weak humoral Ab response Many host response cells, few bacteria Nerve thickening Defined in Plaques Lepromatous leprosy -Strong Ab response, low cellular response -High # of bacteria -Patchy plaques and extensive tissue destruction -disfiguration |
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What caueses Johne's disease?
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Johne's = Chronic wasting disease in cattle (garden hose disease)
Mycobacterium paratuberculosis Koch Postulates have NOT been fulfilled... May have a role in Crohn's disease (spread by meat, milk?) |
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What type of parasites are Rickettsia and Chlamydia?
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OBLIGATE intracellular parasites
Small Gram NEGATIVE outer membrane strenghtened by disulphide cross-linked cysteine rich membrane proteins NON motile, non spore forming Chlamydia lacks biochemically detectable peptidoglycan (though they have the genes for it). Rickettsia has normal peptidoglycan NEVER NF |
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What drug is Chlamydia sensitive to?
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D-cycloserine
suggests that D-ala-D-ala ligase activity (no peptidoglycan) |
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How might you grow Chlamydia in a lab?
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NOT on conventional media (remember intracellular?)
Culture in host cells. Chalmydia requires host-derived ATP (but Rickettsia generates its own) |
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What are the steps of pathogenesis of Chlamydia?
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1. Elementary Body
2. attachment and ingestion 3. phagosome fusion 4. reorganization of Elementary Body to Reticulate Body 5. Multiplication of RB 6. Condensation of RB to EB 7. mature inclusion 8. Extrusion and releaseof infectious EB |
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What disease does each specie of Chlamydia cause?
-C. psittaci -C. pneumoniae -C. trachomatis |
-C. psittaci
Psittacosis -C. pneumoniae acute respiratory infection -C. trachomatis Trachoma (ABC subtype) DEFHIJK subtypes cause: NGUrethritis, cervicitis, endometritis, salpingitis, proctitis, epididymitis, inclusion, conjunctivitis in new borns, infant pneumonia syndrome |
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What disease does each serovar of Chlamydia trahomatis cause?
ABBaC BBaD-K L1, L2, L3 |
ABBaC = Trachoma
BBaD-K = Oculogenital disease (conjunctivitis, urethritis, proctitis, cervicitis) and infant pneumonia L1, L2, L3 = Lymphogranuloma venereum (LGV) |
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What is so special about Chlamyida psittaci?
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-Primarily pathogen of birds and animals (turkey, sheep, pig, cattle problems)
-Human infections are rare, usually in bird handlers. -Disease is psittacosis which manifests as an acute pneumonia that an be severe |
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What is the newly recognized stain of Chalmydia?
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Chlamydia pneumoniae
-wide range of respiratory illness (pharyngitis to pneumonia) -over 50% of US adults have serum Ab to this. Indicates around 100% infection associated with atherosclerosis and adult onset pneumonia |
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What pathogen is associated with the occurance of coronary atherosclerosis and adult onset asthma?
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Chlamydia pneumoniae
In lungs, Intracellular in macrophage, dissemination. build up in veins |
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What is Trachoma?
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A disease caused by Chlamydia trachomatis
-Ocular disease caused by serovars A, B, Ba, and C (endemic in Africa and Asia) not in US -500M infections ww -Disease results from inflammatory damage to the conjunctiva elicited by repeated or persistent ocular infections -Blindness results from mechanical scratching of cornea by disfigured eyelids |
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How is Chlamydia trachomatis transmitted?
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via sexual contact for gential tract infections
Attaches to and invades epithelial cells. Does NOT require breaks in skin membranes to do this. Most common bacterial STI Whoohooo #1!!!!! Servars: DEFHIJK 15% of sexually active women are infected |
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what disease is more purulent: Chlamydia or Gonorrhoea?
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Gonorrhoea for sho. "the clap"
meaning Chlamydia is more asymptomatic cases. |
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Does does a disease from Chlamydia look like?
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-mild purulent inflammation
-destruction of columnar epiethelial cells of cervix , uterus, fallopian tubes, urethra ( rectum nasopharynx, conjunctiva as well) more damaging long term disease is IMMUNE MEDIATED = long term inflammation which gives rise to scarring and fibrosis of local tissues |
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How can Chlamydia prevent fertilization?
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causes build up of scarring that can block the fallopian tube, after salpingitis
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What happens when women are infected with Chlamydia?
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-10% develop PID (pelvic inflammatory disease)
-1% develop infertility or ectopic pregnancy PID = general term form lower abdominal pain in women that usually involves endometritis or salpingitis. Silent PID occurs more frequentyly creating greater likelihood of becoming infertile Infertility result from scarring and occlusion of fallopian tubes (ectopic pregnancy) |
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What did the genome sequencing of Chlamydia trachomatis reveal?
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Presence of type III secretion system
inclusion membrane might be type II secretion apparatuses for injection of molecules into host cell |
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Which parasite is an energy parasite:
Chlamydia or Rickettsia? |
Rickettsia is NOT
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Describe cell morph of Rickettsia-
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more typical gram negative cell wall than Chlam
LPS is present. Stain poorly w/ gram stain so best visualized by Giemsa or Wright's stain replicate freely in cytoplasm of host |
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What causes Rocky Mountain Spotted Fever?
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Ricketsia Rickettsii
transmitted by wood and dog ticks (Dermacentor andersoni and Dermacentor variabilis). the tick is the main reservoir of the pathogen through transovarian infection organism may be in rodents |
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What are the symptoms of Rocky Mountain Spotted Fever?
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After 1 week of being bitten by a tick, early symptoms = fever, headache, chills, muscle pain and nausea
Rash 2-5 days after onset of fever and may be subtle when patient is initially seen by the physician Characteristic Red, spotted rash is not seen until 6th day after initial symptoms Fatal when disease progresses to multiple organ failure (resp, CNS or renal). Organism preferentially infects endothelial cells throughout body causing widespread leakage of blood vessels. Long term sequelae = partial paralysis of lower extremities. Gangrene requires amputation of fingers toes and limbs. |
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How would one dx Rickettsia?
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NOT routinely grown in the lab
difficult to locate and stain on biopsy. Immuno staining common for autopsy Dx made on clinical presentation and detection if anti-Rickettsial Ab Ab are detected by indirect IHC which detect IgM or IgG in blood |
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Epidemic or Louse-borne Tyhpus is caused by...?
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Rickettsia prowazeki
transmitted by human body louse (Pediculus humanis) or by fleas humans = primary reservoir due to poor sanitation and crowded living. Commonly spread through armies. WWI at least 1M deaths b/c of epidemic typhus progression is similar to Rocky Mountain spotted fever but twice as high mortality rates |
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What causes Endemic or Murine Typhus?
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Rickettsia typhi
transmitted by rat or cat fleas slower onset and less mortality. Dr. Ricketts who identified R. rickettsia died of rickettsial tyhphus |
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How is rickettsia similar to Listeria monocytogenes and Shigella flexneri?
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Rickettsia rickettsii and R. typhi exhibit actin-based motility (ABM)
R. prowazekii does not do this Look at confocal to image actin |
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What percentage of US isolates of Neisseria are resistant to penicillin, tetracycline or both?
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33%
2% are resistant to ciprofloxcin (used to be drug of choice) Primary treatment = Ceftriaxone (third generation cephalosporin) |
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What is unique about Neiserria gonorrhoeae's surface molecules?
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They undergo extensive antigenic and or phase variation
-Many thousands of possible combinations -allows it to evade the host immune response -alters binding specificities, helping it bind different tissues to other hosts Net result = we don't develop protective immunity to gonococcal infections (no vaccine) |
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What is the difference between Antigenic and Phase variation?
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Antigenic = alteration of the primary sequence of a protein or the chemical composition of a carbohydrate molecule that results in antigenic differences recognized by the host
Phase Variation= presence/absence (turning on/off) of either a single or multiple virulence or antigenic determinant. A determinant that undergoes phase variation does NOT necessarily undergo antigenic variation |
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What are the different variable components of the gonococcal cell surface?
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Pili = frequency of variability is 1/10 or 1/100
LOS = 1/10^4 Opacity protein = 1/10^4 pili are most variable |
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How does the gonococcal pilin antigen variation work?
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Series of transcriptionally silent pilin gene copies
(pilS1, pilS2, pilS3?) S for silent One expressed pilin gene pilE Homologous recombination occurs between the silent and expressed regions. -transformation of gene conversion -net result is a change in the coding sequence (note that the old sequence is LOST permanently and the new copy is an antigenic variant of the pilus) |
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Tell me the story about Neisseria gonorrhoeae wrt
-Transformation -Gene conversion -Phase Switching |
-Transformation
Donor gonococci actively secretes DNA (T4SS) and DNA can be liberated by autolysis DNA is incorporated into recipient chromosome -Gene conversion Intracellular recombination process this is how components of silent locus are incorporated into the expressed locus -Phase Switching Recombination of pilE can insert a a translational stop codon Transcriptionally active but truncated non-functional protein bald/non-piliated |
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Are there strains of non-piliated Neisseria gonorrhoeae?
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Yes, but they are NEVER isolated from infections
Pili = virulence only exception is from women during menses Certain circumstances during pathogenesis, the bald state may help reduce opsonization by the host anti-pilin antibodies |
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Which pathogen uses phase variation by slipped-strand misparing during DNA replication?
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opa in N. gonorrhoeae
opc in N. meningitidis opa and opc genes contain multpile copies of sequence CTCTT if a repeat is lost or gained, this results in a frame shift and the full protein is not made b/c a stop codon |
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Why do people get repeat infections of GC?
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antigenic variation means repeat infections are common
James Boswell, a Scottish writer, got gonorrhea 17 times in 30 years "Boswell's Clap" |
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Where can gonococci adhere to cause gonococcal disease?
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epithelial cells in the urethra, cervix, uterus, fallopian tubes, rectum, nasopharynx, conjunctiva
Virulence factors assist this adherence and survival at mucosal sites. |
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What are the protein exotoxins of Neisseria gonorrhoeae? Virulence factors?
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NO exotoxins!
Virulence factors: -Pilin (pilE) used with phase/antigenic variation Use: initial binding to epithelial cells -PII (Opa) outer membrane protein, phase/antigenic variation Intimate attachment contributes to invasion of host cell, involved in microcolony formation -LOS outer membrane lipooligosaccharide Mediates bacterium-bacterium attachment (microcolony formation) Elicits inflammatory response: triggers TNF-alpha release that causes scarring of Fallopian Tubes -IgA protease outer membrane protein Evades immune response by cleaving secretory IgA (sIgA) "Gonorrhea Produces Outstanding Lesions In People" |
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What causes the sloughing of fallopian tube cells in gonorrhea induced-PID
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Release of toxic molecules LOS and peptidoglycan-derived cytoxin
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Where is the type IV secretion system encoded in Neisseria gonorrhoeae?
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Gonococcal Genetic Island (GGI)
18 genes for type IV secretion 7 genes encode putative DNA processing 32 genes with not matches in the database The island is in 80% of gonoccal strains and NOT in N. mmeningitidis |
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What type of secretion system does Neisseria gonorrhoeae use?
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Type IV !!!
secretes proteins, DNA, cytotoxin |
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What is the significance for the DNA secretion of Neisseria gonorrhoeae?
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Before this was found, people thought that free DNA was taken up by gonococci from lysed cells
this secreted DNA can contribute to the spread of antibiotic resistance genes and antigenic variation |
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|
What are the two spirochetes covered?
|
Borrelia and Treponema
|
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|
So, tell me a bit about the Borrelia Cell structure:
|
-structurally gram Negative (but stains poorly.
must use Giemsa or Wright stain MOTILE due to endoflagellar structure in periplasm. Use Bright Field microscop to look at! (cannot do this with treponema) No LOS/LPS |
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|
How would you grow Borrelia?
|
In clinical specimens
Borrelia recurrentis is found in the blood Borrelia burgdorferi is rarely visualized in clinical specimens Can grow them in the lab -slow grow -use complex media -microaerophilic conditions -30C optimal growth temp |
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|
How does Borrelia move?
|
periplasm flagella
moves in a helical wave |
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|
What causes Borrelia Relapsing Fever?
|
Requires Arthropod vector
Borrelia recurrentis -epidemic -louse borne Borrelia hermsii -endemic -tick borne Bacteremia 1 wk after bit fever, headache 3-7 days long |
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|
What happens in Relapsing Fever
|
Caused by Borrelia
recurrentis and hermsii 1. # of bacteria decrease over the week along with symptoms 2. another period of bacteremia 3. increase anti-borrelia Ab causes decrease 4. relapse comes from antigenic variation in Variable Major Protein (VMP) |
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Which form of Relapsing Fever is more severe?
|
-Epidemic form
Borrelia recurrentis causes deathin in up to 40% of people humans are the only reservoir the Endemic form is less severe with many animal reservoirs |
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|
What causes Lyme Disease?
|
Borreial burgdorferi
Endemic in WI One of the most common arthropod diseases (transmitted from hard shelled ticks) |
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|
Who transmits Borrelia burgdorferi?
|
Only ticks
-Ixodes scapularis in WI this tick feeds on white-footed mouse and the white-tailed deer -immature nymph and young adults are responsible for disease in humans very small, and has painless bite |
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|
What is the 2 year life cyle of the Deer tick (Ixodes scuplaris)
|
eggs hatch to larvae, feed on white-footed mouse, and turns into nymph. this can eat humans or more mice.
hatch into young adults, bite humans, mouse, deer, then lays eggs |
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Who is wider, Borrelia or Treponema?
|
Borrelia! so this means it can be visualized in bright field microscopy using Wright or Giemsa stain
(but B. burgdorferi is rarely seen in direct clinical specimens) |
|
|
what kind of chromosme does Borrelia have?
|
Linear chromosome and plasmids
Major outer surface protein (Osps) encoded on linear plasmids High rate of recombination producing antigenic variation Osps variation has no impact on pathogenesis |
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|
Which pathogen has Osp's that we worry about?
|
Osp = Outer Surface Protein
Borrelia has these on the outer membrane It is similar to other gram negative except -No LPS in outer membrane -produces large number of lipoproteins (many Osp's) -have endo-periplasmic flagella (EF) |
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How in the world does Borrelia generate Antigenic variation??
|
It has linear plasmids remember.
These encode vlsE. Portions of partial copies are moved in and out of expressed region to make unique recombinants. (silent regions go to expressed regions) Antigenic variation of vlsE allows B. burgdorferi to evade host immune responses |
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|
What are the stages of Lyme Disease?
|
Stage 1:
-Erythema migrans (expanding skin lesion 3-30 days) -fever, headach, malaise, chills, muscle pain, stiff neck Stage 2: -Only occurs in 10-20% of individuals -Secondary lesions, arthritis, Bell's palsy, neurological and cardiac symptoms Stage 3: -Neurological symptoms and arthritis -Arthritis resolves in 60% of cases -10% have severe destructive arthritis (antibiotic resistant) -Bacteria NOT recovered at this stage, symptoms due to reactive immune response |
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|
How can you Dx Lyme disease?
|
-Early dx with Erythema Migrans and can recall being bitten
-Not usually recovered in blood or tissues -use symptoms, history and serology (anti IgG Borrelia Ab are more reliable than IgM) |
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|
How should you remove a tick?
|
use tweezers to grasp tick near the mouth parts as close to the skin
pull steadily upward do NOT use kerosine, matches or petroleum jelly |
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|
Is there a lyme disease vaccine?
|
yes, but it failed
-contained OspA (outer surface lipoprotein) -ospA only found in Borrelia infected ticks but prevented infection -claims that it caused arthritis |
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|
What is the cause of Syphilis?
|
Treponema pallidum
transmitted in utero from mother to fetus |
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|
What is the cellular structure of Treponema pallidum ?
|
thin, long, helical structure
periplasmic flagella like Borrelia Gram Negative in nature |
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|
Can you grow Treponema pallidum in culture?
|
-very hard
will NOT grow in tissue culture or complex media animal modesl only produce aspects of disease we don't really know that the virulence factors are... |
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|
What are the three stages of syphilis?
|
Primary Stage:
-Chancre -Lesions at site of infection where Treponema is replicating -Painless site of neutrophil and macrophage infiltration Secondary: Disseminated Stage -2-12 weeks after primary -organism spreads throughout body -general body rash -lesions as local sites of replication Tertiary: -can occur years after secondary -chronic inflammatory disease (granulomatous lesions in bones, brain, heart, skin) -Neurosyphilis (chronic inflammation of the CNS, can cause paralysis, demential and sensory loss there are latency periods in between each |
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|
What is Congenital Syphilis?
|
transplacental transmission from mother to fetus
-can result in deformed / stillborn fetus -if child is delivered, it can enter a secondary stage which can progress to tertiary |
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|
How can you get Syphilis?
|
STI
-any contact with primary or secondary lesions can cause infection -humans are the ONLY reservoir -bacterium sensitive to low temperatures and drying (can't get this from a toilet seat) -THIRD most common STD |
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|
So how would you try to Dx Syphilis?
|
-Clinical presentation
-DARK field microscopy on material from the lesions (look for helical organisms0 -use Immunofluorescene with anti-treponemal antibodies cannot be cultured in the lab (not biochemical or antibiotic assays) |
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|
What are the non-treponemal tests for Dx of Syphilis?
|
1. Test for Ab to cardiolipin
-Ab produced by humans to compounds released from damaged cells in response to Treponema can aggregate w/ cardiolipin 2. VDRL (Venereal Diseae Research Laboratory) -use patient sera to cause cardiolipin to flocculate (generate Ag-Ab complex visualize) -subject positive/negative problem -many false positives |
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|
What are the treponema tests for Dx of Syphilis?
|
Fluorescent Treponemal Ab Absorption (FAT-Abs)
-measure presence of specific anti-Treponema pallidum Ab in serum Immunoblotting - T. pallidum antigen separated by electrophoresis - Use patient serum and measure reactivity of Ab to Ag |
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|
What is significant about the Tuskegee Experiments?
|
African American men given Syphilis until 70's
no treatment used heavy metal poisoning penicillin shown to be effective treatment |
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|
What causes Whooping Cough?
|
Bortdetella pertussis
|
|
|
How did they finally get success with the whooping cough vaccine?
|
Bortdetella pertussis
They identified the appropriate "subcellular" element which caused no side effects while providing protective immunity |
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|
Who is credited in the discovery of Antibody-mediated lytic activity in sera (complement)?
|
Jule Bordet
cultivated Bortdetella pertussis for the first time and helped establish it as the cause of whooping cough |
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|
Tell me about the bacteriology of Bortdetella pertussis:
|
Small, Gram Negative, bacillii that are AEROBIC
-does not grow on common media. must use Bordet-Genou medium -grows slowly with colonies appearing after 3 days Bortdetella pertussis is a strict human parasite (adults may the the reservoir) |
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|
Who found the Adjuvant Effect?
|
Pearl Kendrick
included Aluminum adjuvant as wll as diphtheria and tetanus toxoids into one DTP vaccine |
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|
Which pathogen (Haemophilus influenzae or Bortdetella pertussis) is capable of systemic spread from respiratory tract into the brain, bloodstream and joins?
|
Haemolphilus influenze disseminates
Bortdetella pertussis colonizes a limited site (tracheobronchial epithelium) and the disease occurs b/c there is systemic spread of exotoins secreted by the organism from the site of infection Death in children w/ whooping cough is most often due to pneumonias caused by secondary invaders such as Strep pneumo So Haemophilus spreads and Bordetella spreads its exotoxins |
|
|
How might one acquire a whooping cough?
|
infection is initiated by inhalation of aerosol droplets produced by sneezing, infected individuals. this is HIGHLY contagious
|
|
|
What are the stages of whooping cough (caused by Bortdetella pertussis)?
|
1. Catarrhal
-runny nose, sneezing, fever, malaise - 1-2 weeks - organism CAN be isolated from patient 2. Paroxysmal coughing -multiple coughs followed by inspiratory gasp, then whoop -last 2-4 weeks -vomiting -organism is difficult to recover 3. Convalescence - symptoms fade but this is when secondary infections occur |
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|
What are the virulence factors for Bordetella pertussis?
|
1. Pertussis Toxin (Ptx):
- A-B type toxin - ADP-ribosylation of host G-protein - modifies signal transdxn - net effect is to block the function of different immune effector cells in host (macro, neutro) 2. Filamentous hemagglutiinin (FHA): - cell surface attachment factor that is believed to promote adherence to B. pertussis to the tracheal ciliated cells 3. Adenylate cyclase toxin - bifunctional toxin First, it can interalize into host cell and cause toxin-mediated derailment of sig transdxn by enzymatically increase [cAMP] Second, at higher [], it possesses a cytolytic activity (hemolysin) 4. Tracheal cytoxin -after attachment to cilia tips of tracheal cells, it destroys ability of those cells to move materials upward, including bacterial cells -toxin consists of basic subunit of peptidoglycan |
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|
In what unique way does Bordetella pertussis reuse peptidoglycan subunits?
|
-Peptidoglycan subunits are normally reused (recycled) but B. pertussis subunits are secreted extracellularly rather than imported back into the cell for new rounds of synthesis
this is vital for its Tracheal cytotoxin |
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|
How might one treat and prevent Bordetella pertussis?
|
Treatment
- Antibiotics do not ameliorate the cause of the disease -treatment is purely supportive in terms of trying to relieve the symptoms of the disease and prevents 2ndary infections Hope for subcellular vaccine which will give better compliance |
|
|
DTP vaccine stands for...
|
Diphtheria (toxoid)
Pertussis = crude envelope fraction, adverse reactions occur with 1/100k Tetanus = toxoid |
|
|
What are the three genera within the family Pasteurellaceae?
|
-Haemophilus
-Actinobacillus -Pasteurella Family is small gram (negative) bacilli often coccal-bacilli shape Facultative anaerobes that are nutritionally fastidious they are NOT free living. They are all obligate parasites of mucosal membranes |
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|
Tell me about the Haemophilus cellular structure:
|
typical gram negative cell envelope
endotoxin differs from enteric LPS in that it is LOS = lipooligosccharide this lacks repeating O-antigen carbohydrates Many, but not all Haemophilus influenzae isolates are encapulsated with polysaccharides |
|
|
What is the different in Haemophilus influenzae strains?
|
based on capsule type
six types a-f b isolates are historically most serious systemic disease Nonencapsulated strains commonly referred to as non-typeable strains are are associated with otitis and sinusitis |
|
|
How would you grow Haemophilus influenzae in culture?
|
Haemophilus influenzae requires encriched media with different blood components.
1. Hematin = "X-factor" 2. nicotinamide adenine dinucleotide (NAD) = "V-factor" need for X and V factors are used to identify Haemolphilus species in the lab Haemophilus influenzae is grown in a nutrient agar called Chocolate agar. this releases X and V factors from RBC's |
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|
What organism demonstrates satelliting in plate culture?
|
Haemophilus influenzae
seen in throat culture plates as small colonies surrounding the colony of an organism like Staph that secreted growth factors from erythrocytes |
|
|
What is the reservoir for Haemophilus influenzae?
|
they are obligate mucosal parasites
perhaps endogenous infections, but not necessarily. But outbreaks of disease are due to the importation and exposure to new epidemic strains |
|
|
What happened to children before the Haemophilus influenzae vaccine?
|
1/200 children got the invasive disease before the age of 5
Meningitis was most common causing brain damage and even mental retardation |
|
|
What can Haemophilus influenzae cause?
|
invasive, systemic disease is caused by isolates that are encapsulated, especially the b capsular type
responsible for 90% of systemic disease such as: -meningtitis -bacteremia -cellulitis -epiglottis HIB vaccine reduced Hib disease greatly (Haemophilus influenzae type b) |
|
|
who is most susceptible to Haemophilus influenzae?
|
Children under age of 5 (mostly 4-18 months)
but kills by meningitis and pneumonia In developing countris, Hib is a problem |
|
|
Which pathogen causes Acute epiglottiitis?
|
Haemophilus influenzae
sudden onset of inflammation and swelling of the top of the throat leads to extreme breathing difficulties leads to suffocation where emergency tracheotomy is required MASH episode with Radar and Father Mulcahy perform a trach on the road directed by Hawkeye using the barrel of a pen as the airway (bic pen trach) |
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|
What do the nontypeable Haemophilus influenzae isolates cause?
|
Otitis media
Bronchitis Sinusitis (bacteremia is rare) Pneumonia can be caused by both encap and nonencap isolates. Esp when the nonencap causes bronchitis first increased risk of pneumonia |
|
|
What Haemophilus causes conjunctivitis?
|
Haemophilus influenzae biotype aegyptius
easily spread among young children, esp Pink Eye outbreaks Adenoviruses are another cause of this type of disease |
|
|
What STI is associated with Haemophilus?
|
Haemophilus ducreyi
STI is infrequent in US but common in Africa Nearly a week after exposure, a small lesion appears that develops into a painful ulcer and there can be subsequent inguinal lymphadenopathy due to spread of bacteria individuals with genital lesions are thought to be at greater risk of contraction HIV |
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|
What are the virulence factors for Haemophilus?
|
1. Capsule
-for typeable isolates (esp Hib) -acts at anti-phagocytic factor -needed for passing through epithelial layes -invasion of meninges 2. IgA Protease -like mucosal pathogens (neisseria) produces extracellular protease which has unique ability to degrade IgA -facilitates colonization of mucosal surface by destroying Ab that would block attachment 3. Pili -nontypeable isolates are piliated and this is though to enhance their ability to colonize the host -surface proteins (HMW's = High Molecular Weight proteins) which appear to be homologous to the adhesions used by Bordetella pertussis no known exotoxins Has exoproteins instead (bind host Fe-binding protein hemepexin) LOS = endotoxin associated with toxicity of respiratory cilia that would facilitate colonization in respiratory tract LOS undergoes phase/antigenic shift "Hemophilus Can Induce Penis Envy" |
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|
What can the endotoxin of Haemophilus influenzae do? (it's endotoxin-mediated toxicity)
|
-fever
-leukopenia followed by leukocytosis -activation of complement -thrombocytopenia -disseminated intravascular coagulation -decreased peripheral circulation and perfusion to major organs -shock -death |
|
|
How can you treat Haemophilus influenzae?
|
sensitive to antibiotics a
|
|
|
What are the vaccine components for:
-diphtheria -tetanus -petussis -Haemophilus influenzae -Neisseria meningitisis -Bacillus anthrasis -yersinia pestis -M. TB |
-diphtheria= toxoid
-tetanus= toxoid -petussis = killed cell / crude cell envelop fraction -Haemophilus influenzae = capsule polysaccharide, protein conjugate -Neisseria meningitisis = capsule polysaccharide -Bacillus anthrasis = killed cell -yersinia pestis = killed cell -M. TB = live attenuated bacille (Calmette-Guerin) for M. bovis |
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|
What is the prototype or classic example of an opportunistic pathogen?
|
Pseudomonas aeruginosa
gram negative rod, aerobe |
|
|
Chemical side bonds that are formed when the sulfur atoms in two adjacent protein chains are joined together and can only be broken by chemicals not broken by heat or water.
|
Disulfide bonds
|
|
|
Pseudomonas is motile
T/F |
TRUE!
polar flagella :)) |
|
|
Pseudomonas aeruginosa is nonfermentative
T/F |
TRUE!
nonfermentative aerobes gets energy from oxidative degradation of sugars capable of growing in the absence of O2 but its energy is not gained by fermentation ! readily grows on lab media |
|
|
what can Pseudomonas aeruginosa use as a carbon source?
|
a WIDE RANGE of organic compounds
grow at wide temperature range 4-40C |
|
|
What organism produces green halos surrounding the colonies due to release of blue (pyocyanin) and yellow (fluorescein) pigments?
|
Pseudomonas aeruginosa
pigments fluoresce and with a long wave lenght UV lanp this means wounds infected may glow in the dark |
|
|
What are the culture characteristics of Pseudomonas aeruginosa?
|
Pseudomonas aeruginosa when grown in the lab produces a fruity grape-like smell that can be detected on the breath of patients
wide range of nutritional sources and wide temp range make this ubiquitous and free living these grow in sinks, flower vases, shower heads, even in hospital disinfectants The first patent awarded for a genetically engineered microorganism was for a pseudomonas that was isolated to clean up oil spills |
|
|
What organism is notorious for biofilms?
|
Pseudomonas aeruginosa
1. Planktonic cells 2. Motility, adhesins, and environmental signals 3. acyl HSL signal 4. mature biofilm Acyl-homoserine lactone serves as a quorum signal where its secretion and accumulation within an increasing population of cells leads to regulation of genes needed for biofilm production |
|
|
why is Pseudomonas aeruginosa particularly bad in Cystic Fibrosis patients?
|
these strains are often prodigious producers of extracellular polysaccharide material made of alginate
this gives the colonies a mucoid appearance hard to treat w/ antibiotics |
|
|
What are the virulence factors for Pseudomonas aeruginosa?
|
-this organism is enigmatic b/c it has many different virulence factors but is again relatively benign (unless there is an underlying disease or break in innate defense)
-adhesive pili -tip of flagellum has a cap protein that binds mucin -produces multiple toxins: exotoxin A -produces elastases (LasA and LasB) which proteolytically degrade different tissue proteins leading to tissue destruction -two different cytolysins -pyocanin pigment catalyzes superoxide and peroxide prodution and oxidative damage to tissues ACTECP All Creepy Fat Truckers Enjoy Corny Porn |
|
|
What is the fxn of Pseudomonas aeruginosa Exotoxin A
|
ADP-ribosylation
IDENTICAL TO DIPHTHERIA TOXIN inhibit protein synthesis by taking nicotinamide adenine dinucleotide (NAD) splitting it and covalently attaching adenosine diphosphate ribose (ADP-ribose) to the elongation factor 2 protein (EF-2) necessary for translocation of nascent proteins on the ribosome blocks protein synthesis single molecule an kill a cell |
|
|
which organism has a toxin that is identical to diphtheria toxin?
|
Pseudomonas aeruginosa
blocks protein synthesis ADP-ribosylation of elongation factor 2 (EF-2) using NAD |
|
|
what are the most common clinical situations of a Pesudomonas aeruginosa infection?
|
1. cystic fibrosis
2. burns > septicemia 3. osteomyelitis following trauma 4. infections of patients with indwelling catheters (IV lines and bladder) biofilms! 5. rapid destruction of the eye (contact lenses) 6. folliculitis (skin infections) 7. bed sores 8. diabetics at risk of rapidly progressing wound and ear infections 9. intravenous drug users get rapidly fatal endocarditis and septic osteomyelitis 10. patients who become neutropenic at risk of septicemia, pneumonia and wound infections 11. urinary tract infection / urosepsis / septic shock |
|
|
What is significant about a Brazilian model?
|
her feet and hands were amputated following a drug resistant infection and died.
Pseudomonas aeruginosa infection initially dx with kidney stones, UTI spread |
|
|
What organism gives decubitus?
|
Pseudomonas aeruginosa
massive skin lesions. |
|
|
what is the prognosis of patients with drug resistant Pseudomonas aeruginosa infections?
|
patients are neutropenic and so cannot clear bacterial cells well. prognosis is not good
in CF patients, organism is NOT really growing in intimate association w/ patient cells, they are caught up in the capsular material and mucus control of these infections is very difficutl due to pervasive nature of Pa |
|
|
How are Campylobacter and Helicobacter related?
|
-gram negative
-spiral shape -low guanosine and cytosine content (low GC) in DNA -inability to ferment or oxidize carbohydrates -microaerophilic growth |
|
|
which two Camplylobacter species are responsible for gastroenteritis?
|
Campylobacter jejuni
-most important cause of gastroenteritis Campylobacter coli -less common but prominent in Africa and Asia |
|
|
What Campylobacter specie causes systemic infections
|
Campylobacter setus ssp. fetus
bacteremia meningtitis septic abortions (even in sheep and cattle) |
|
|
what group of patients is most susceptible to Campylobacter infections?
|
20-29 year olds
|
|
|
Describe Campylobacter:
|
gram negative
curved rod polar flagella if cells combine, they form a "seagull" appearance difficult to see in gram stain b/c so thin. Can pass through .45um filter |
|
|
What should you keep in mind when you grow Campylobacter?
|
-nutritionally fastidious
-require microaerophilic conditions (reduced oxygen tension) but not considered anaerobes They also grow better at 42C than 37C hmmm, interesting |
|
|
what is one of the few pathogens where the flagella plays a role in pathogenesis?
|
Campylobacter jejuni
|
|
|
What is a main virulence factor of Campylobacter jejuni?
|
Flagella
-undergoes BOTH phase and antigenic variation Disease is brought about by destruction of mucosal surfaces of lower small intestine and colon Diarrhea stools appear to be due to malabsorption of fluids in contrast to a cholera disease where there is a net loss of H2O from intestines S |
|
|
What do Campylobacter jejuni infection stools look like?
|
stools contain leukocytes and blood in dysentery phase
organism invades sub-epithelial layers (lamina propria) of intestine but never bactermia |
|
|
What are the different components of the Campylobacter jejuni cell surface?
|
1. Capsule
-highly variable polysaccharide -important for: viurlence, epithelial cell adherence and cell invasion 2. LOS -lipooligosaccharide -highly variable -role in serum resistance, epithelial cell adherence and cell invasion -display molecular mimicry of neuronal gangliosides (linked to Guillain-Barre syndrome) 3. Flagellum -required for colonization -virulence and epithelial invasion -acts as secretion apparatus for invasion antigens -flagellin is modified by O-linked glycosylation -modification required for assembly N-linked glycosylation system modifies some periplasm and outer membrane proteins N-linked glycan is important for colonization and epithelial cell adherence and invasion |
|
|
Where would you find a reservoir for Campylobacter?
|
Normal flora in intestine of animals
fecal contamination of food and water leads to dissemination to humans Dogs (puppies) significant reservoirs Poultry unpasteurized milk |
|
|
what is the infective dose for Camplylobacter jejuni and coli?
|
relatively low about 1000 organisms
|
|
|
What pathogen is Guillain-Barre Syndrom associated with?
|
Campylobacter
|
|
|
What is the cause of Guillan Barre syndrom and what are the symptoms?
|
Campylobacter LOS!
-thought to be immune-related sequelae of bacterial infection -myelin sheath of multiple peripheral nerves are damaged resulting in paralysis -LOS is similar to neuronal gangliosides and immune reactivity results in paralysis -recovery can take 6 months -most common cause of rapidly acquired paralysis |
|
|
what organism is the cause of chronic gastric inflammation (gastritis) ?
|
Helicobacter pylori
gram negative, helical once thought to be a species of Campylobacter |
|
|
What is the reservoir for Helicobacter pylori?
|
probably not animals
more like person to person |
|
|
Who made the association between Helicobacter pylori infections with gastritis, peptic ulcers and gastric cancer?
|
Dr. Barry Marshall and Robin Warren
Marshall swallowed a culture and began to get gastritis 2005 nobel prize winners |
|
|
Well what does Helicobacer look like, and how do we see it?
|
Gram negative
very thin and tiny so hard to see under light microscopy use electron microscopy |
|
|
how can you grow Helicobacter pylori?
|
requires enriched media for growth
microaerophilic grows best at 37 but not 42 (in contrast to Campylobacter) slow grower 4-7 days for a colony highly mobile due to polar flagella (unusual b/c sheathed in a membrane covering) |
|
|
What is the primary virulence factor of Helicobacter pylori?
|
-urease production (clinical dx)
ammonia produced by breakdown of urea protects in stomach acidity pH=2 Large amounts of ammonia and CO2 produced are toxic to host cells leads to persistent gastric infection urease produced by H. pylori is most active urease known among bacteria |
|
|
does Helicobacter pylori have a secretion system?
|
yes. type IV
Pathogenic strains have additional virulence factors encoded on the chromosome designated as the cag pathogencity island |
|
|
What genes are encoded on the cag pathogencity island of Helicobacter pylori?
|
-Type IV secretion system (related to conjugal transfer)
-CagA virulence factor and some other proteins -Vacuolating toxin (VacA) |
|
|
what is the importance of CagA in Helicobacter pylori?
|
CagA is an effector molecule that is translocated into a host cell then is phosphorylated on tyorosine residues by members of Src-kinase
induces signaling pathways that lead to dramatic morphological changes in host cell |
|
|
what does a type IV secretion system do?
which organisms have it? |
Type IV secretes protein or DNA and protein
-Helicobacter pylori (releases CagA) -Bordetella pertussis (Ptx) -Neisseria gonorrhoeae -Agrobacterium -Legionella pneumophilia Four Hookers Bake Noodles Lustfully Altogether |
|
|
What are the virulence factors of H. pylori?
|
1. VacA = vacuolating cytotoxin
causes production of large vacuoles throughout cytoplasm 2. Flagella 3. CagA 4. Nitrogen/Urease 5. LPS Listen, Vaginal-Cock Fun Not Allowed LPS, VacA, CagA, Flagella, Nitrogen Metabolism Enzymes |
|
|
What month is Campylobacter jejuni disease highest? at what age?
|
summer months June-Aug
20-29 y/o |
|
|
Which bacteria have LOS in their cell wall?
|
Lost Cat Needs Home
LOS: -Campylobacter -Neisseria -Haemophilus |
|
|
What are the virulence factors for Helicobacter pylori?
|
Currently, Vaginal Fun Love Not Allowed
-CagA -VacA -LPS -Flagella -Nitrogen metabolism / urease -Adherent factor |
|
|
What are the virulence factors of Campylobacter?
|
Campylobacter Loves Fisting Nuns
-Capsule -LOS -Flagellum -N-linked glycosylation |
|
|
What are the virulence factors of Bordetella pertussis?
|
Pertussis Fucks Asian Trannies
-Pertussis toxin -Filamentous Hemagglutinin (FHA) -Adenylate cyclase toxin -Tracheal toxin |
|
|
What are the virulence factors of Pseudomonas virulence?
|
All Creepy Fat Truckers Enjoy Corny Porn
-Adhesive Pili -Cap on Flagella -Toxin = ExotoxinA -Elastase -Cytolysin -Pyocyanin pigment |
|
|
What are the virulence factors of Neisseria gonorrhoeae?
|
Gonorrhea Produces Outstanding Lesions In People
-Pilin (PilE) -Opa (Outer membrane protein) -LOS (endotoxin) -IgA Protease |
|
|
What are the virulence factors for Haemophilus influenzae?
|
Haemophilus Can Induce Penis Envy
-Capsule -IgA protease -Hemapexin -Pili (nontypeable) -Endotoxin = LOS |
|
|
Copperheads
|
Those who were totally against the war, and denounced president Lincoln. The most famous of the copperheads was Clement L. Valandigham, who harshly denounced the war but was imprisoned, then banished to the South.
|
|
|
Describe the toxin from Clostridium tetani?
|
Tetanospasmin = Tenanus Neurotoxin
This is A-B type toxin Causes spastic paralysis = Lock Jaw Amino end = zinc metalloproease C term = bind neuronal cell |
|
|
Which gram(-) bacteria has a general cell structure but no LPS or LOS?
|
Borrelia recurrentis
has Osp's, periplasmic flagella, and vlsE instead. (Can't have it all) |
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How would you visualize Borrelia vs. Treponema?
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Borrelia = bright field (Giemsa or Wright stain)
Treponema = darkfield w/ anti-treponemal antibodies |
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Which organism has actin-based motility?
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Rickettsia rickettsii
Rick must act now! |
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Why does Relapsing Fever relapse??
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Epidemic = louse borne Borrelia recurrentis
Endemic = tick borne Borrelia hermsii Due to Variable Major Protein |
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which organism has linear chromosomes?
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Borrelia burgdorferi
Osp's have high variability (but they do not contribute to pathogenesis so the disease does not relapse) vlsE is highly variable and causes pathogenesis |
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What protein on Borrelia burgdorferi undergoes antigenic variation and is responsible for immune system evasion??
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Osp's have no role in pathogenesis!
vlsE is the main one here! |
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Which bacteria has a type III secretion system?
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Chlamydia trachomatis
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Which Bordetella pertussis toxin kills the tracheal cells?
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Tracheal Cytoxin!
Remember... Pertussis Fucks Asian Trannies -Pertussis Toxin A-B type toxin ADP-ribosylation of G-protein blocks function of different immune effector cells in the host (macrophages and neutrophils) -FHA (Filamentous Hemagglutinin) Cell surface attachment factor adheres to tracheal ciliated cells -Adenylate cyclase toxin bi-functional internalized and derails sig trans, increasing intra cAMP also, possesses cytolytic activity (hemolysin) -Tracheal cytoxin attaches to tracheal epithelial cells, destroys ability of these cels to move material upward. this is the basic subunit of peptidoglycan |
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What pathogen uses subunits of peptidoglycan as a toxin?
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Bordetella pertussis
Tracheal cytoxin |
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What two molecules contribute to ciliated cell death on N. gonorrhoeae infections?
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LOS and peptidoglycan
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what do the different subtype of Chlamydia trachomatis cause?
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A, B, Ba, C = Trachoma
D-K = dysuria, cervititis, etc L 1-3 = Lymphogranuloma venereum |
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for one pathogen, we have a vaccine, but it can't cover all serotypes b/c of Polysialic acid, an antigen found in humans. What pathogen?
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Neisseria meningiditis
type B this causes most of the cases in the US Vaccine works for A C Y W135 |
