Eat, kill or die: when amoeba meets bacteria

doi:10.1016/j.mib.2008.05.005

Current Opinion in Microbiology

Volume 11, Issue 3, June 2008, Pages 271-276

https://doi.org/10.1016/j.mib.2008.05.005 Get rights and content

The core function of the innate immune response, phagocytosis, did not evolve first in metazoans but rather in primitive unicellular eukaryotes. Thus, though amoebae separated from the tree leading to metazoan shortly after the divergence of plants, they share many specific functions with mammalian phagocytic cells. Dictyostelium discoideum is by far the most studied amoeba, and it is proving useful to analyze phagocytosis and intracellular killing of bacteria. Since the basic mechanisms involved appear extremely conserved, Dictyostelium provides novel insights into the function of many new gene products. Bacterial pathogenicity was certainly largely developed to resist predatory amoebae in the environment, and this accounts for the fact that a large number of bacterial virulence traits can be studied using Dictyostelium as a host. This provides a particularly powerful system to analyze the complex interactions between pathogenic bacteria and host cells, where both the Dictyostelium host and the bacteria can be manipulated genetically with relative ease.

Section snippets

Born to kill: the professional phagocyte

It is classical in metazoan organisms to distinguish professional from occasional, nonprofessional phagocytes, but both pale in front of amoebae, which throughout their life ingest, kill, and digest microorganisms at a rate of at least one per minute. Initial studies of phagocytosis focused on the dynamics of the actin cytoskeleton, a crucial parameter during cell locomotion and phagocytic engulfment. Acanthamoeaba and Dictyostelium played a pioneering role in establishing the function of the

Phagocytosis and adhesion: integrins in amoebae?

Adhesion to a particle is the first step of the phagocytic process. At least three membrane proteins (Phg1, SadA, and SibA) [9, 10, 11] are essential for cell adhesion and phagocytosis, and SibA is probably the main adhesion receptor [11]. Interestingly, SibA presents features of integrin β chains, notably an extracellular VWA domain and a conserved cytoplasmic domain. On the cytoplasmic side, like integrins, SibA binds to a complex between talin and the FERM-containing myosin VII, both of

A well-orchestrated maturation program

The endocytic and phagocytic pathways of Dictyostelium exhibit marked similarities with mammalian cells [16], and have been extensively studied [17, 18]. A number of studies have defined the exact composition of phagosomes at each step. During the formation of phagosomes some membrane proteins are selectively excluded [19], while others are delivered in the first minutes following phagosome closure [20^••]. This is then followed by successive maturation steps involving sequential delivery and

Killing: Dictyostelium likes it raw

For amoebae as well as for mammalian phagocytes, phagocytosis is a prelude to intracellular killing, a still largely mysterious phenomenon. Lysosomal hydrolases are delivered to the bacteria-containing phago-lysosomes and were therefore initially believed to play a key role in killing. Cathepsin G and elastase are involved in the intracellular killing of S. aureus and C. albicans, respectively [23], and secreted β-hexosaminidase has been implicated in the killing of mycobacteria [24]. The study

And then things turned ugly…

Imagine a planet populated with the ancestors of present-day bacteria, fungi, and plants, all shyly hidden within a rigid cell wall. Imagine amoebae irrupting in this rather peaceful world, capable of engulfing and killing virtually any other cell. What a feast it must have been for the predators, and what a terrible fate for cells ill-equipped to deal with such a situation. All microorganisms must have been under strong selective pressure to develop the traits needed to survive an encounter

A long list of pathogens

Not surprisingly, many pathogens have turned out to use similar virulence mechanisms to fight Dictyostelium and mammalian hosts (reviewed recently in [28, 29]). These include extracellular pathogens (e.g. Pseudomonas aeruginosa), or bacteria capable of intracellular replication like Legionella. In several cases, Dictyostelium has been instrumental in analyzing bacterial virulence, allowing for example the discovery of the role of the type VI secretion system of Vibrio cholera pathogenesis [30,

Surviving infection: resistance genes

Phagocytic cells are confronted frequently with bacteria, and the result of this encounter largely determines the pathogenic potential of any given bacteria. Little is known today about cell-intrinsic resistance mechanisms: only a few potential resistance genes are identified, and their exact function often remains unclear. One of the best studied examples is N-Ramp1, a metal transporter present in the phagosomal membrane in mammalian cells, whose loss leads to enhanced replication of some

Conclusion

How many ways are there for a phagocyte to kill bacteria? How many ways for pathogenic bacteria to escape killing? What determines phagocyte resistance to pathogens? In Dictyostelium, the answer to each of these questions will be a long list of gene products. As these lists start growing, we will begin to discern how many different strategies phagocytes have evolved to survive in the great game of evolution.

References and recommended reading

Papers of particular interest, published within the annual period of review, have been highlighted as:

• of special interest
•• of outstanding interest

Acknowledgements

We would like to thank members of our research groups for helpful discussions, and Bianca Habermann (Bioinformatics, Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany) for her help with protein homology searches. This work was supported by grants from the Fonds National Suisse pour la Recherche Scientifique (to PC and TS). Both of our laboratories participate in the NEMO network, supported by the 3R Foundation.

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View full text

Eat, kill or die: when amoeba meets bacteria

Section snippets

Born to kill: the professional phagocyte

Phagocytosis and adhesion: integrins in amoebae?

A well-orchestrated maturation program

Killing: Dictyostelium likes it raw

And then things turned ugly…

A long list of pathogens

Surviving infection: resistance genes

Conclusion

References and recommended reading

Acknowledgements

Cell

J Biol Chem

J Biol Chem

Curr Biol

Nature

Proc Natl Acad Sci U S A

PLoS Pathog

Traffic

Sur la lutte des cellules de l’organisme contre l’invasion des microbes

Annales de l’Institut Pasteur

The genome of the social amoeba Dictyostelium discoideum

Nature

The actin cytoskeleton of Dictyostelium: a story told by mutants

J Cell Sci

Evolutionarily conserved modules in actin nucleation: lessons from Dictyostelium discoideum and plants. Review article

Protoplasma

Unconventional myosins, actin dynamics and endocytosis: a menage a trois?

Traffic

Coronin, an actin binding protein of Dictyostelium discoideum localized to cell surface projections, has sequence similarities to G protein beta subunits

EMBO J

Definition of family of coronin-related proteins conserved between humans and mice: close genetic linkage between coronin-2 and CD45-associated protein

DNA Cell Biol

SadA, a novel adhesion receptor in Dictyostelium

J Cell Biol

An adhesion molecule in free-living Dictyostelium amoebae with integrin beta features

EMBO Rep

Talin-null cells of Dictyostelium are strongly defective in adhesion to particle and substrate surfaces and slightly impaired in cytokinesis

J Cell Biol

Rap1 controls cell adhesion and cell motility through the regulation of myosin II

J Cell Biol

Fusion and fission events in the endocytic pathway of Dictyostelium

Traffic

Involvement of the AP-1 adaptor complex in early steps of phagocytosis and macropinocytosis

Mol Biol Cell

Morphology and dynamics of the endocytic pathway in Dictyostelium discoideum

Mol Biol Cell