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The evolution of chronic infection strategies in the α-proteobacteria

Nature Reviews Microbiology volume 2, pages 933–945 (2004)Cite this article

Key Points

The α-subdivision of the Proteobacteria is a very large and diverse group of Gram-negative microorganisms. They show great variability in metabolic capacities and inhabit diverse ecological niches. The authors discuss the different mechanisms used by these bacteria to associate with eukaryotic hosts, either as symbionts or as pathogens.

The genomes of the α-proteobacteria vary in both size (from 1 to 9 Mb) and organization (from single circular replicons to multiple replicons, both circular and linear). The genome of the common ancestor of the α-proteobacteria was estimated to contain 3,000–5,000 genes. Two major trends associated with the conversion of this ancestral gene pool into the genomes of the modern species can be recognized: intracellular bacteria associated with invertebrates, animals and humans have evolved by gene loss, whereas the soil-growing, plant-associated bacteria have evolved through genome expansion.

Despite the close phylogenetic relationships between these bacteria, there is no clear 'common mechanism' that allows these bacteria to interact with their eukaryotic hosts. Is this surprising considering the diversity of the hosts? The strategies and mechanisms used by these bacteria to infect the host, avoid host defences and then adapt to the host are described, compared and contrasted.

A recurrent feature of the interaction of α-proteobacteria with their hosts is an effect on host-cell proliferation, creating a new niche in which, or on which, the bacteria can survive. This involves inhibiting cell death and then inducing cell proliferation. Here again, each bacterium uses a different mechanism, ranging from the production of diverse molecules that affect host cell biology, often affecting growth hormones, to 'genetically manipulating' the host cell to induce tumorigenesis.

Abstract

Many of the α-proteobacteria establish long-term, often chronic, interactions with higher eukaryotes. These interactions range from pericellular colonization through facultative intracellular multiplication to obligate intracellular lifestyles. A common feature in this wide range of interactions is modulation of host-cell proliferation, which sometimes leads to the formation of tumour-like structures in which the bacteria can grow. Comparative genome analyses reveal genome reduction by gene loss in the intracellular α-proteobacterial lineages, and genome expansion by gene duplication and horizontal gene transfer in the free-living species. In this review, we discuss α-proteobacterial genome evolution and highlight strategies and mechanisms used by these bacteria to infect and multiply in eukaryotic cells.

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Figure 1: Variation in genome sizes and lifestyles in the α-proteobacteria.
Figure 2: The road to a chronic infection.
Figure 3: Root hair and nodule infection by rhizobia.
Figure 4: Schematic representation of the invasion and intracellular-survival strategies of selected α-proteobacteria.
Figure 5: Intracellular replication niches.

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Acknowledgements

We thank J. V. Cullimore and C. Boivin (LIPM) and A. Vergunst (Leiden University) for helpful discussions; D. Gage (University of Connecticut), T. Timmers (LIPM), P. Cossart (Institut Pasteur), D. Bouchon (CNRS UMR6556) and C. Dehio (Biozentrum Basel) for providing images; and C. Felix and G. Martin (CNRS UMR6556), A. Huber and C. Ronson (University of Otago) for sharing unpublished data. We regret that space limitations have not allowed us to cite all the work published in the field. Work in the authors' laboratories is supported by INRA, CNRS and the Toulouse genopole (to J.B.), the Swedish Research Council, the Swedish Foundation for Strategic Research, the Knut and Alice Wallenberg Foundation and the 5th EU-framework program 'Quality of Life' (to S.G.E.A.), and INSERM, the 5th EU-framework program, Vaincre la Mucoviscidose, Universite de Montpellier 1 (BQR), La Region Languedoc Roussilon and La ville de Nimes (to D.O'C.).

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Authors and Affiliations

  1. Laboratory of Plant Microbe Interactions (LIPM), CNRS-INRA, BP27, Castanet-Tolosan, 31326, Cedex, France

    Jacques Batut

  2. Department of Molecular Evolution, Evolutionary Biology Center, Uppsala University, Norbyvagen 18C, Uppsala, 752 36, Sweden

    Siv G. E. Andersson

  3. INSERM U431, UFR Medecine, CS83021, Avenue JF Kennedy, Nimes, 30908, Cedex 02, France

    David O'Callaghan

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  1. Jacques Batut
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Correspondence to David O'Callaghan.

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DATABASES

Entrez

Agrobacterium rhizogenes

Agrobacterium tumefaciens

Anaplasma (Ehrlichia) phagocytophilia

Bartonella henselae

Bartonella quintana

Bordetella pertussis

Bradyrhizobium japonicum

Brucella melitensis

Brucella suis

Caulobacter crescentus

Ehrlichia chaffensis

Escherichia coli

Mesorhizobium loti

Mycobacterium tuberculosis

Neisseria meningitidis

Pseudomonas aeruginosa

Rhizobium sp. NGR234

Rhizobium leguminosarum

Rickettsia conorii

Rickettsia prowazekii

Sinorhizobium meliloti

Treponema pallidum

Xanthomonas campestris

FURTHER INFORMATION

Jacques Batut's laboratory

Siv G. E. Andersson's laboratory

Glossary

CHEMOORGANOTROPHY

The derivation of energy by metabolizing organic molecules.

PHOTOTROPHY

A process that involves the gaining of energy from light.

CHEMOLITHOTROPHY

The use of CO, CO2 or carbonates as the sole source of carbon for cell biosynthesis, and the derivation of energy from the oxidation of reduced inorganic or organic compounds.

PERICELLULAR

Bound to the cell surface.

NODULE PRIMORDIUM

A cluster of undifferentiated and actively dividing cells in the root cortex that is formed in response to Nod factors from which the nodule meristem will form.

NOD FACTORS

Substituted lipo-chitooligosaccharides synthesized by rhizobia in response to flavenoids and related compounds in plant exudates. They induce changes in plant cell biology that are required for infection and nodulation.

PHRAGMOSOME

A cytoplasmic structure anchoring the nucleus and the mitotic apparatus to the future division plane in pre-mitotic plant cells.

BACTEROID

Symbiotic form of rhizobia that have left the infection thread. Fully differentiated bacteroids are non-dividing and nitrogen-fixing. Bacteroids are separated from the plant cell cytoplasm by a peribacteroid membrane and a peribacteroid space.

TYPE IV PILI

Found on many bacteria, these mediate bacterial adhesion, biofilm formation and horizontal gene transfer. They are dynamic polymers that elongate and retract resulting in 'twitching motility'.

PLACENTAL TROPHOBLASTS

A specialized cell type covering the mammalian blastocyte.

ZIPPER MECHANISM

Bacterial pathogens invade mammalian cells with two distinct phenotypes. The 'zipper' phenotype, as seen with invasin-mediated entry of Yersinia or internalin-mediated entry of Listeria, is morphologically characterized by 'zippering' of a closely apposed host membrane around the bacterial surface. This is in contrast to the 'trigger' phenotype, which is seen with the entry of Salmonella and Shigella, whereby large membrane projections or ruffles are formed.

LIPID RAFTS

Localized regions with high cholesterol and glycosphingolipid content within cell membranes. These microdomains are focal points for proteins and have roles in a wide range of biological processes. Many bacteria, viruses and parasites use lipid rafts to enter mammalian cells. Vesicles that are derived from raft domains seem to traffic independently of other pathways and do not fuse with endosomes and lysosomes. This allows the pathogens to remain in a safe, non-hostile environment.

CRAFT ASSAY

(Cre Reporter Assay for Translocation). Allows the detection of translocation of bacterial virulence factors directly into host or recipient cells as translational fusions to the Cre site-specific recombinase. The Cre fusions mediate recombination at specifically designed lox-target sites in the recipient cell genome, activating the expression of a reporter gene allowing visualization or stable selection.

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Batut, J., Andersson, S. & O'Callaghan, D. The evolution of chronic infection strategies in the α-proteobacteria. Nat Rev Microbiol 2, 933–945 (2004). https://doi.org/10.1038/nrmicro1044

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