Our laboratory is interested in understanding the cellular and molecular
mechanisms that allow microbial pathogens to survive and multiply within the
hostile host cells. We use Legionella pneumophila, the causative agent of
Legionnaires’ disease as a model organism. This bacterium is a facultative
intracellular pathogen capable of growing in a vacuole within macrophages as
well as fresh water amoebae. After uptake, the Legionella-containing vacuole
(LCV) in its early phase evades fusion with the lysosomal network and later is
transformed into a compartment with characteristics of rough endoplasmic
reticulum. Essential to the biogenesis of this replicative vacuole is the
Dot/Icm Type IV protein secretion system that injects a large number of effector
proteins into target host cells. These effectors modulates a variety of host
cellular processes, such as remodeling of phagosomal membrane, vesicular
trafficking, cell death, stress response thus allowing the establishment of the
replicative compartment that supports bacterial growth. Our current focus is to
analyze biochemical and cell biological activities conferred by these proteins
and their roles in promoting the unique trafficking of the Legionella-containing
vacuole in phagocytic cells. In particular, we are interested in identification
of host proteins whose activities are modulated by substrates of the Dot/Icm
system and the roles of such modulation in intracellular bacterial growth.
Caption for images found in the header: Translocation of effectors into host cell by L. pneumophila in early phase of infection . Host nucleus and bacterium were labeled in red and the effector SidC was labeled in green (Left image). Note the diffusion of SidC from the bacterial phagosome. B. Formation of a large replicative vacuole by L. pneumophila in late phase of infection (Right image). In both cases, note the perinuclear localization of the vacuole.