Molecular Mechanisms of Legionella pneumophila Pathogenesis

Amoeba

• single-celled eukaryotic microorganisms

• 200-700 microns in length

• eat using pseudopodia

  • only eat bacteria, algae, or fungal cells

Legionella pneumophila

• proliferates within amoebae

• gram-negative rod shape

• fresh water and soil

• facultative intracellular bacterium

Legionnaires disease

• number 1 bacterial cause of waterborone disease

• inorder to kill, water needs to be heated to >60 C or 140 F

The Philly Killer

• legionnaires disease at American Legion Convention at the Bellevue Stratford Hotel

• caused 221 infections and 34 deaths

• caused by hotels abandoned nuclear bomb shelter, spread by air-conditioned system through the hotel

Who was responsible for identifying the Philly Killer

• Joseph McDade

  • identified rod-shaped bacterium

Legionnaires disease

• >50 years aged, immunocompromised, smokers

• incubation period: 2-14 days

• fatal in 10-15% of cases

Pontiac Fever

• healthy people, as well as those with underlying disease

• incubation period: hours-3 days

• 95% of people exposed develop symptoms

• flu like illness, no pneumonia

What was used to treat Legionnaires disease

• Macrolides

  • inhibit 50S subunit ribosome

  • Azithromycin

• Fluoroquinolones

  • inhibits DNA gyrase

  • Moxifloxacin

Where does Legionella pneumophila proliferate

• macrophages

• replicates inside amoebae and human macrophages

  • bothe are professional phagocytes

Legionella pneumophila

• effector proteins are substates of Dot/Icm secretion system

• gnome comprises 3000 genes

• over 300 genes encode effector proteins

• translocated into host cytosol by the Dot/Icm type IV secretion system

summary of Legionella pneumophila

• fresh water bacteria that infects amoeba

• virulent and motile when they reach stationary growth phase

• causes severe pneumonia

• infects alveolar macrophages and resista degradation

• injects effector proteins into host cytosol through T4SS

• hijacks host cell pathway without disrupting host survival

How do we model infection in the lab

• Amoeba

  • Acanthamoeba castellani

  • Dictyostelium discoideum

• Non-phagocytic cell lines

  • HeLa cells

• Macrophages

  • U937

  • THP-1