MMI 301: Listeriosis/Diphtheria

Joseph Lister

Mononuclear leukocytes that infiltrate during infection

• -Small gram-positive rod
• -Facultative anaerobic
• -Motile at 25 degree and below
• -Beta-Hemolysis/Catalase (+)
• -Grow at 4 degrees and in high salt

Minor febrile gastroenteritis, bacteremia, spontaneous abortion

meningitis, death

meningitis, sepsis, death

rarely: bacteremia, sepsis, CNS infection, minor febrile gastroenteritis

• Positive Gram Stain
• Cold enrichment
• Motility
• beta-Hemolysis

• Zoonotic fecal-oral foodborne infection
• Associated with unpasteurized cheeses, ready-to-eat meats/foods, produce
• Can replicate in fridge, survive in freezer

• Listeriolysin O (LLO)
• Actin polymerization factor ActA

• Crosses intestinal barrier to cause invasive disseminated disease
• Replicates inside of epithelial cells, hepatocytes, bactericidal macrophages
• Not effected by antibody/complement responses because intracellular

• 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

• 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

• Ampicillin/Amoxacillin and Gentamycin
• 20-30% fatality rate with treatment

• 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.

• Requires cellular mediated, humoral doesn't work.
• Infection leads to long term protective immunity
• No use for vaccine, chemotherapeutic is in making

• 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

• koryne-club
• Bacterion- little rod
• Small, Gram-positive bacilli (often irregular shape)
• Non-motile
• Facultative aerobe
• Catalase +
• Urease -

• 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

• Gram + rods in throat swab
• Black colonies on potassium tellurite agar
• methylene blue stain in Loeffler's coagulated blood agar

• 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

• 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

• 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

• 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

• DTap: Diphtheria, Tetanus, acellular Pertussis
• DT: Diphtheria, Tetanus
• Tdap: Tetanus, diptheria, acellular pertussis
• Td: Tentanus, diphtheria

• 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