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  • Review Article
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The Legionella pneumophila replication vacuole: making a cosy niche inside host cells

Key Points

  • Legionella pneumophila is a Gram-negative intracellular pathogen of both amoebae and humans that grows in lung macrophages. The intracellular replication strategy of this bacterium, which involves growth in a membrane-bound compartment called a vacuole, seems to be similar in all cell types in which it grows.

  • A protein translocation apparatus that encodes more than 20 proteins, called Dot/Icm, is required for formation of the replication vacuole and intracellular growth. Proteins move through the apparatus across membranes in contact with the bacterium, and are thought to manipulate host cell proteins that are involved in host cell secretory traffic.

  • Eighty five translocated protein substrates of Dot/Icm have been identified, but there are probably many more. The targets of several have been identified, and they include proteins that modulate the activation state of Arf1 and Rab1 and are involved in vesicle trafficking in host cells, as well as proteins that antagonize host cell death pathways.

  • Mutations in single translocated substrates rarely result in strong defects in intracellular growth. This has led to the model that there is considerable functional redundancy among the substrates.

  • A model is provided to attempt to explain how L. pneumophila acquired such a diverse set of translocated substrates.

Abstract

The pathogenesis of Legionella pneumophila is derived from its growth within lung macrophages after aerosols are inhaled from contaminated water sources. Interest in this bacterium stems from its ability to manipulate host cell vesicular-trafficking pathways and establish a membrane-bound replication vacuole, making it a model for intravacuolar pathogens. Establishment of the replication compartment requires a specialized translocation system that transports a large cadre of protein substrates across the vacuolar membrane. These substrates regulate vesicle traffic and survival pathways in the host cell. This Review focuses on the strategies that L. pneumophila uses to establish intracellular growth and evaluates why this microorganism has accumulated an unprecedented number of translocated substrates that are targeted at host cells.

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Figure 1: Legionella pneumophila modulates the trafficking of its vacuole to establish a replicative niche.
Figure 2: The Legionella-containing vacuole.
Figure 3: The Dot/Icm translocation apparatus.
Figure 4: Legionella pneumophila manipulates host cell death and survival pathways.

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Acknowledgements

We thank M. Machner, V. Auerbuch Stone and E. Creasey for their review of the manuscript. M.H. was supported by a postdoctoral fellowship from the National Institute of Allergy and Infectious Diseases and R.R.I. is an investigator at the Howard Hughes Medical Institute.

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Correspondence to Ralph R. Isberg.

Supplementary information

41579_2009_BFnrmicro1967_MOESM1_ESM.pdf

Supplementary information S1 (table): Dot/Icm translocated substrates A: Substrates based on similarity to eukaryotic proteins (PDF 247 kb)

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DATABASES

Entrez Genome Project

Dictyostelium discoideum

Drosophila melanogaster

Escherichia coli

Legionella longbeachae

Legionella pneumophila

Pseudomonas syringae

Saccharomyces cerevisiae

Entrez Protein

CpxR

DotC

DotD

DotF

DotG

DotH

DotL

DotM

DotN

DrrA

IcmS

IcmW

LvgA

PmrA

RalF

RpoS

FURTHER INFORMATION

Ralph R. Isberg's homepage

Glossary

Functional redundancy

Two proteins that perform a similar or related function; for example, when the activity of one protein can compensate for the absence of the other.

Phagolysosome

A membrane-bound organelle that is formed through the fusion of a phagosome with a lysosome.

COPI (Coatomer protein complex I)

A protein complex that coats the outer surface of vesicles that travel between the endoplasmic reticulum (ER)-to-Golgi intermediate compartment or are recycled from the Golgi complex to the ER.

Dominant negative

A mutation which leads to a phenotype that persists in the presence of the wild-type allele.

Retrograde

The trafficking of vesicles in a direction that starts from the host cell surface and ends in the endoplasmic reticulum (ER); for example, traffic from the Golgi complex to the ER.

Autophagy

The process by which a cell degrades its own cytoplasmic constituents by packaging them into a membrane-bound compartment and fusing the resulting vacuole with the lysosome.

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Isberg, R., O'Connor, T. & Heidtman, M. The Legionella pneumophila replication vacuole: making a cosy niche inside host cells. Nat Rev Microbiol 7, 13–24 (2009). https://doi.org/10.1038/nrmicro1967

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