Seminar

Legionella pneumophila - A master manipulator of host cell membrane trafficking GTPases

Matthias P. Machner, PhD

Legionella pneumophila, the causative agent of Legionnaires’ pneumonia, survives and replicates within human immune cells. The bacterium bypasses the degradative endo-lysosomal compartment and establishes a camouflaged replication vacuole (LCV) by hijacking proteins and membranes from the host cytosol. The molecular processes underlying these manipulatory events are poorly understood. Dr. Matthias P. Machner will present two studies describing how vesicle transport GTPases of the Rab family are directly targeted by L. pneumophila effector proteins during infection. The first scenario describes a cascade of events that manipulates Rab1, a regulator of vesicle trafficking to the Golgi compartment. L. pneumophila recruits and activates Rab1 through GDP/GTP exchange, and subsequently modifies Rab1 through the covalent addition of adenosine monophosphate (AMP), a process known as AMPylation, thereby locking it in the active conformation. Dr. Machner will present data showing that another effector protein named SidD catalyzes removal of AMP from Rab1, a process known as de-AMPylation, thereby priming Rab1 for inactivation and removal from the LCV membrane. In a second example Dr. Machner will describe a newly discovered interaction between a Legionella effector and the host cell GTPase Rab5, the key regulator of early endosomal fusion in eukaryotes. Their studies revealed that L. pneumophila uses Rab5 to direct an effector protein with phospholipase activity to endosomes where it alters the lipid composition of the endosomal membrane, rendering them incapable of fusion. Dr. Machner will present a model explaining how manipulation of these two Rab GTPase-regulated host pathways may allow L. pneumophila to survive and replicate within the otherwise hostile environment of a macrophage.