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Listeria's Namesake
Joseph Lister
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Monocyte
Mononuclear leukocytes that infiltrate during infection
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Listeria Morphology
- -Small gram-positive rod
- -Facultative anaerobic
- -Motile at 25 degree and below
- -Beta-Hemolysis/Catalase (+)
- -Grow at 4 degrees and in high salt
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Listerial Diseases in Pregnant Women:
Minor febrile gastroenteritis, bacteremia, spontaneous abortion
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Listerial Diseases in Neonates/fetus:
meningitis, death
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Listerial diseases in the Immunosuppressed
meningitis, sepsis, death
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Listerial diseases in healthy adults
rarely: bacteremia, sepsis, CNS infection, minor febrile gastroenteritis
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Diagnosing Listeria
- Positive Gram Stain
- Cold enrichment
- Motility
- beta-Hemolysis
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Sources of Listerial Infection
- Zoonotic fecal-oral foodborne infection
- Associated with unpasteurized cheeses, ready-to-eat meats/foods, produce
- Can replicate in fridge, survive in freezer
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Listeria Virulence Factors
- Listeriolysin O (LLO)
- Actin polymerization factor ActA
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Listeria monocytogenes Infection/Pathogenesis
- Crosses intestinal barrier to cause invasive disseminated disease
- Replicates inside of epithelial cells, hepatocytes, bactericidal macrophages
- Not effected by antibody/complement responses because intracellular
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Listeriolysin O
- Essential for Virulence
- Binds to cholesterol containing membranes
- Attaches pores through which cytoplasm can escape
- Lyses phagosome
- Most active at 5.5 pH
- -This means it is best at lysing phagosomes, not host cell membranes, keeping their environment intact
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ActA
- Essential Virulence Factor for bacteria
- Facilitates cell to cell spread
- Uses hosts cytoskeleton
- Similar to other intracellulars: Shigella, Ricketsia, Burkholderia
- Used to understand host cells
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Listeria treatment
- Ampicillin/Amoxacillin and Gentamycin
- 20-30% fatality rate with treatment
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Listeria Outbreaks
- 2011 (Jensen Farms Cantalope): 147 infected, 33 dead, 1 miscarriage, 60 day incubation time
- 2012 (Frescolina Marte Brand Ricotta Salata Cheese): 20 infected, 4 dead.
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Listeria monocytogenes Immunity
- Requires cellular mediated, humoral doesn't work.
- Infection leads to long term protective immunity
- No use for vaccine, chemotherapeutic is in making
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L. monocytogenes Immunotherapy
- Immunotherapy: Utilizes body's natural immune system to fight infection
- Use attenuated strains (deltaActA/inlB or deltaprfA+hly) to safely immunize
- Engineer L. mono to express tumor antigens (HPV-E7/mesothelin)
- Stimulate antigen specific T-cell response
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Corynebacterium diphtheriae Morphology
- koryne-club
- Bacterion- little rod
- Small, Gram-positive bacilli (often irregular shape)
- Non-motile
- Facultative aerobe
- Catalase +
- Urease -
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Symptoms of Diphtheria
- Respiratory:
- Mostly in children
- Fever/Sore throat
- Pseudomembrane/pharynx
- -composed of fibrin, leukocytes, necrotic epithelial cells, and diphtheria
- Cutaneous:
- Minor lesions to non-healing ulcers
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Diphtheria Diagnosis
- Gram + rods in throat swab
- Black colonies on potassium tellurite agar
- methylene blue stain in Loeffler's coagulated blood agar
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Diphtheria Toxin (DT)
- Encoded by temperate beta-phage
- Expression induced upon iron starvation
- Is AB toxin
- -three subunits B/T/A: Binding, Translocation, Active
- -Transloction needs phagosome acidification
- Receptor discovered through cDNA library cloning
- -HB-EGF heparin-binding epidermal growth factor
- DT enters cells and ADP-ribosylates EF-2
- -EF-2 required for protein synthesis
- -Uniquely modified histidine in EF-2 called diphthamide is target of DT
- -Inhibition causes cell death
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Diphtheria History
- Killed 80% of children under ten in early colonies
- In 1920s, 200,000 cases/13-15,000 deaths
- Worldwide Today: 30,000 cases/3,000 dead
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Diphtheria Treatment
- Antitoxin: Neutralizes toxin (antibodies)
- Penicillin/Erythromycin: eliminate colonizing bacteria, prevent additional secretion
- DPT Vaccine: ensure long term protective immunity, infection does not always cause immunity
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Diphtheria Vaccine History
- 1890-antitoxin treatment by Emil von Behring (horse/guinea pig)(first nobel prize in med.)
- 1894-Early use of antitoxin (horse) in US
- 1914: William Park shows combo antitoxin/toxin can confer immunity
- 1923: Gaston Ramon/Alexander Glenny develop DT toxoid using heat/formalin.
- 1964: Adjuvant added to the DTP vaccine
- 2003: last documented case of Diphtheria in US
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Current Diphtheria Vaccines in US
- DTap: Diphtheria, Tetanus, acellular Pertussis
- DT: Diphtheria, Tetanus
- Tdap: Tetanus, diptheria, acellular pertussis
- Td: Tentanus, diphtheria
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Important Factoids
- Listeria monocytogenes is an important foodborne pathogen that primarily affects pregnant women and still causes outbreaks in
- the US
- L. monocytogenes requires Listeriolysin O and ActA to cause disease
L. monocytogenes is being developed as an immunotherapeutic tool
- Corynebacterium diphtheriae causes
- the disease Diphtheria through the activation of cell death by circulating Diphtheria toxin
Diphtheria Toxin works by inhibiting protein synthesis in host cells through the ADP ribosylation of EF-2
Inactivated Diphtheria Toxin is a highly effective vaccine that has eradicated Diphtheria in the US since 2003
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