Content area
Full Text
Figure 1. Functional redundancy and host range expansion. (A) Linear schematic of the Legionella genome that depicts the seven genomic loci that contain no essential genes. The total number of genes and the number of Icm/Dot translocated substrates within each cluster is noted for the wild-type Legionella strain and for the pentuple strain, which contains simultaneous deletions in five of the identified clusters. Clusters 2, 4, 6 and 7 could not be removed completely. The number of genes that remain after genetic manipulation are indicated. (B) The wild-type Legionella strain is able to replicate in amoeba and primary murine bone marrow-derived macrophages from A/J mice. The pentuple strain, on the other hand, is not able to replicate in amoeba, indicating that one or more of the nonessential genes is specifically required for replication in amoeba.
(C) A schematic of distinct amoebal species - Dictyostelium discoideum (Dd) , Hartmannella vermiformis (Hv) and Acanthamoeba castellanii (Ac) - within the aquatic environment of a fresh water pond is shown. Legionella mutants that contain deletions of individual clusters exhibit distinct intracellular growth phenotypes in different amoebal species, suggesting that the presence/absence of these clusters define the amoeba host range.
(Figure omitted. See article PDF.)
Figure 2. Legionella Icm/Dot translocated substrates manipulate host vesicle trafficking pathways. Legionella evades fusion with endosomal compartments and generates an intracellular compartment that is reminiscent of the ER. The acquisition of ER components is mediated by IDTS that hijack host vesicle trafficking pathways to promote fusion between ER-derived vesicles and the LCV. Legionella -driven processes are highlighted using red arrows, while host-driven processes are depicted with black arrows. These translocated substrates include the guanine exchange factors RalF and DrrA/SidM, which recruit Arf1 and Rab1 to the LCV membrane. Several translocated effectors modulate the activity of Rab1. DrrA AMPylates (∼) Rab1 and works with the t-SNARE syntaxin 3 and the v-SNARE Sec22b to promote fusion between ER vesicles and the LCV. The effector LidA is thought to act as a tether that stabilizes the interaction between activated Rab1 and the LCV. SidD is a deAMPylase. AnkX modifies Rab1 by adding a PC (#) moiety, which is reversed by the activity of Lem3. LepB is a Rab1 GTPase-activating protein that inactivates Rab1 and triggers its removal...