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Review
. 2012 Jun;20(6):299-306.
doi: 10.1016/j.tim.2012.03.005. Epub 2012 Apr 9.

Exploitation of evolutionarily conserved amoeba and mammalian processes by Legionella

Tasneem Al-Quadan  1 , Christopher T Price, Yousef Abu Kwaik
Affiliations
Review

Exploitation of evolutionarily conserved amoeba and mammalian processes by Legionella

Tasneem Al-Quadan et al. Trends Microbiol. 2012 Jun.

Abstract

Legionella pneumophila proliferates within various protists and metazoan cells, where a cadre of ∼300 effectors is injected into the host cell by the defect in organelle trafficking/intracellular multiplication (Dot/Icm) type IVB translocation system. Interkingdom horizontal gene transfer of genes of protists and their subsequent convergent evolution to become translocated effectors has probably enabled L. pneumophila to adapt to the intracellular life within various protists and metazoan cells through exploitation of evolutionarily eukaryotic processes, such as endoplasmic reticulum-to-Golgi vesicle traffic, phosphoinositol metabolism, AMPylation, deAMPylation, prenylation, polyubiquitination, proteasomal degradation and cytosolic amino- and oligo-peptidases. This is highlighted by the ankyrin B (AnkB) F-box effector that exploits multiple conserved eukaryotic machineries to generate high levels of free amino acids as sources of carbon and energy essential for intracellular proliferation in protists and metazoan cells and for manifestation of pulmonary disease in mammals.

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Conflict of interest statement

The authors declare no competing financial interests.

Figures

Figure 1
Figure 1
Evolutionarily conserved eukaryotic pathways exploited by Legionella in amoeba and mammals. (a) Farnesylation modification of eukaryotic proteins. Proteins that contain CaaX motif are recognized by the cytosolic farnesyl transferase (FTase), which modifies the protein by the addition of a 15-carbon farnesyl group to the conserved cysteine residue within the C-terminal CaaX motif. The farnesylated proteins are trafficked to the endoplasmic reticulum (ER) where the aaX tripeptide is cleaved by the Ras-converting enzyme-1 (RCE1) protease, followed by methylation of the farnesyl group by the isoprenyl cysteine carboxyl methyl transferase (IcmT) enzyme. The modified protein is subsequently targeted to specific membranes. (b) The eukaryotic ubiquitination pathway. Ubiquitin modification is an ATP-dependent process involving the sequential action of three enzymes (E1–E3). Ubiquitin activating enzyme (E1) activates ubiquitin (red circle) via the generation of a high energy thioester bond between ubiquitin and an E1 cysteine residue. The activated ubiquitin is then transferred to ubiquitin conjugating enzyme (E2). The final step of the ubiquitination is where substrate-specific ligase (E3) binds simultaneously to E2 and the substrate, resulting in transfer of ubiquitin monomer from the E2 enzyme to a target protein. The fate of the modified protein is determined by the lysine linkages utilized in polyubiquitination.
Figure 2
Figure 2
Ankyrin B (AnkB)-mediated generation of amino acids through promoting proteasomal degradation of amoeba and mammalian hosts. Upon translocation of AnkB by the defect in organelle trafficking/intracellular multiplication (Dot/Icm) type IV secretion system, AnkB is farnesylated by the three host enzymes farnesyl transferase (FTase), Ras-converting enzyme-1 (RCE1) and isoprenyl cysteine carboxyl methyl transferase (IcmT) that are recruited to the Legionella-containing vacuole (LCV) by the Dot/Icm system. Upon farnesylation, AnkB is anchored into the cytosolic face of the LCV membrane, where it interacts with the SCF1 E3 ubiquitin ligase complex and acts as a platform for the docking of K48-linked polyubiquitinated proteins to the LCV. The K48-linked polyubiquitinated proteins are targeted for proteasomal degradation that generates short peptides that are rapidly degraded by cytosolic oligo- and amino-peptidases. This results in generation of high levels of free amino acids that are imported to the LCV by various amino acid (AA) transporters, such as SLC1A5. The whole process is highly conserved and is essential for intracellular proliferation of Legionella in amoeba and human cells and for intrapulmonary proliferation in mice. Adapted from [53].
Figure 3
Figure 3
Exploitation of host cell lipid phosphatidylinositol (PI) derivatives to anchor Legionella pneumophila effectors. Many defects in organelle trafficking/intracellular multiplication (Dot/Icm)-translocated effectors such as SidC, SidM, LidA and LpnE are anchored to the Legionella-containing vacuole (LCV) membrane through PI(4)P or PI(3)P to interfere with signal transduction and promote host vesicle trafficking.
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References

    1. Molmeret M, et al. Amoebae as training grounds for intracellular bacterial pathogens. Appl Environ Microbiol. 2005;71:20–28. - PMC - PubMed
    1. Harb OS, et al. From protozoa to mammalian cells: a new paradigm in the life cycle of intracellular bacterial pathogens. Environ Microbiol. 2000;2:251–265. - PubMed
    1. Gao LY, et al. Utilization of similar mechanisms by Legionella pneumophila to parasitize two evolutionarily distant host cells, mammalian macrophages and protozoa. Infect Immun. 1997;65:4738–4746. - PMC - PubMed
    1. Abu Kwaik Y, et al. Invasion of protozoa by Legionella pneumophila and its role in bacterial ecology and pathogenesis. Appl Environ Microbiol. 1998;64:3127–3133. - PMC - PubMed
    1. Luo ZQ. Legionella secreted effectors and innate immune responses. Cell Microbiol. 2012;14:19–27. - PMC - PubMed

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