Matthias P. Machner, Ph.D.
Head, Unit on Microbial Pathogenesis
Cell Biology and Metabolism Program (CBMP)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
18 Library Drive
Building 18, Room 101
Bethesda, MD 20892
Our main research goal is to obtain a detailed understanding of the molecular mechanisms by which the pathogenic bacterium Legionella pneumophila can manipulate host cells during infection.
L. pneumophila is a Gram-negative bacterium that is commonly found within freshwater reservoirs as a natural parasite of amoeba. When inhaled by humans L. pneumophila can cause a potentially fatal pneumonia known as Legionnaires' disease. The pathogen establishes a replication vacuole within infected cells that avoids lysosomal fusion. The organism hijacks cargo vesicles of the infected host cell and transforms its phagosome into specialized membrane compartment that resembles host cell rough endoplasmic reticulum. Within this protective niche L. pneumophila can replicate to high numbers, eventually lyse the spent host cell and infect neighboring cells.
L. pneumophila delivers a large number of proteins, so called effectors, into the host cell via the Dot/Icm type IV secretion system (T4SS). Little is known about the molecular function of these translocated substrates. However, bacterial mutants with a defective Dot/Icm system are avirulent, underscoring the importance of the effector proteins for L. pneumophila pathogenesis. Our research is aimed at characterizing the molecular function of these effector proteins and to determine their role during host cell infection. For more information, click here.