Our main research goal is to obtain mechanistic insight into the virulence strategies of microbial pathogens. As a model organism we use the bacterium Legionella pneumophila, the causative agent of a potentially fatal respiratory infection known as Legionnaires' disease. Contrary to what its name may imply, Legionnaires’ disease occurs in individuals of all ages, including children who receive respiratory therapy, newborns who recently underwent surgery or under-water birth, and children who are immune-compromised. We are committed to the in-depth analysis of mechanisms that allow L. pneumophila to exploit the human host and cause disease. Insights gained from these studies will ultimately improve our ability to better diagnose, prevent, and fight Legionnaires’ disease and related illnesses, thereby contributing to the success of NICHD’s mission.
Upon inhalation of contaminated water droplets, L. pneumophila enters the lung and is phagocytosed (taken up) by alveolar macrophages, specialized immune cells. Instead of being degraded by these cells, the pathogen establishes a protective membrane compartment, the Legionella-containing vacuole (LCV). Within this intravacuolar niche, L. pneumophila can replicate to high numbers before it kills the host cell and infects neighboring cells.
Intracellular survival of L. pneumophila depends on the activity of more than 300 proteins, or effectors, that are injected into the host cell, where they create conditions favorable for infection. L. pneumophila mutants that are defective in effector protein delivery fail to escape endolysosomal degradation, underscoring the key role of microbial effectors for bacterial virulence. Our goal is to obtain a detailed mechanistic insight into the regulation and function of L. pneumophila effectors by investigating host-pathogen interactions at a molecular, cellular, and structural level. Deciphering the virulence program of this dangerous pathogen will set the stage for the development of novel therapeutics aimed at treating or preventing Legionnaires' disease and related illnesses.