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  • Review Article
  • Published:

Anaplasma phagocytophilum and Ehrlichia chaffeensis: subversive manipulators of host cells

Nature Reviews Microbiology volume 8, pages 328–339 (2010)Cite this article

Subjects

Key Points

  • Anaplasma spp. and Ehrlichia spp. cause several emerging human infectious diseases. They are obligate intracellular bacteria that reside in cells of haematopoietic origin in mammals and also in tick cells. This Review focuses on recent A. phagocytophilum and E. chaffeensis studies related to their pathogenesis, observed primarily from the bacterial perspective.

  • A. phagocytophilum and E. chaffeensis lack genes for the biosynthesis of the lipopolysaccharide and peptidoglycan that activate host leukocytes. Instead, they acquire host cholesterol from the low-density-lipoprotein uptake pathway.

  • Caveolae-mediated endocytosis directs A. phagocytophilum and E. chaffeensis to an intracellular compartment, or inclusion, that does not acquire components of NADPH oxidase nor show similarity to late endosomes or lysosomes. E. chaffeensis inclusions retain early-endosome characteristics, whereas A. phagocytophilum inclusions acquire early-autophagosome characteristics.

  • A. phagocytophilum and E. chaffeensis both have small genomes (approximately 1.2–1.5 Mb) with a low coding capacity for proteins involved in central intermediary metabolism and amino acid synthesis. However, both retained genes for aerobic respiration and for the biosynthesis of all of the necessary nucleotides and most vitamins and cofactors.

  • In A. phagocytophilum there is an expansion of the OMP1–P44 superfamily encoding outer-membrane proteins that are unique to the family Anaplasmataceae. Some of these proteins have been shown to be porins.

  • In cell culture A. phagocytophilum and E. chaffeensis undergo developmental stages known as dense-cored cells and reticulate cells. The ApxR and EcxR transcription factors are unique to the family Anaplasmataceae, and three two-component systems are involved in regulating the intracellular development of the species in this family.

  • Expression of the type IV secretion system is developmentally regulated, and two secreted effectors have been shown to regulate protein tyrosine kinases and cellular apoptosis.

Abstract

Anaplasma spp. and Ehrlichia spp. cause several emerging human infectious diseases. Anaplasma phagocytophilum and Ehrlichia chaffeensis are transmitted between mammals by blood-sucking ticks and replicate inside mammalian white blood cells and tick salivary-gland and midgut cells. Adaptation to a life in eukaryotic cells and transmission between hosts has been assisted by the deletion of many genes that are present in the genomes of free-living bacteria (including genes required for the biosynthesis of lipopolysaccharide and peptidoglycan), by the acquisition of a cholesterol uptake pathway and by the expansion of the repertoire of genes encoding the outer-membrane porins and type IV secretion system. Here, I review the specialized properties and other adaptations of these intracellular bacteria.

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Figure 1: A phylogram of the family Anaplasmataceae, based on 16S ribosomal RNA gene sequences.
Figure 2: The Anaplasma phagocytophilum and Ehrlichia chaffeensis infection cycles.
Figure 3: The intracellular niches of Anaplasma phagocytophilum and Ehrlichia chaffeensis in human cells.
Figure 4: The p44 and omp1–p28 loci.
Figure 5: Proposed intracellular development cycle of Ehrlichia chaffeensis.

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Acknowledgements

I thank all former and current members of my laboratory for their scientific contributions, T. Vojt for preparing the figures, V. L. Popov for the electron micrographs and K. Hayes-Ozello for editorial assistance. I also acknowledge grants from the US National Institutes of Health.

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  1. Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, 1925 Coffey Road, Columbus, 43210, Ohio, USA

    Yasuko Rikihisa

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Supplementary information

41579_2010_BFnrmicro2318_MOESM1_ESM.pdf

Supplementary information S1 | Selected surface proteins from Anaplasma phagocytophilum and Ehrlichia chaffeensis (PDF 267 kb)

Glossary

Caveola

A specialized lipid raft region of the plasma membrane that contains the protein caveolin and forms flask-shaped, cholesterol-rich invaginations of the membrane.

Autophagosome

An intracytoplasmic, membrane-bound vacuole containing elements of a cell's own cytoplasm and membrane proteins that are distinct from phagosomes or other intracellular vesicles. It usually fuses with a lysosome.

Type IV secretion system

A multiprotein complex that mediates the translocation of macromolecules (that is, proteins, DNA or DNA–protein complexes) across the bacterial cell envelope into the extracellular medium or directly into recipient cells.

Himar transposase system

A DNA insertion system using Himar1, which belongs to the mariner family of transposable elements. Himar1 requires no host-specific factors for transposition and has been frequently used as a prokaryotic genetic tool.

Alternative σ-factor

A σ-factor that is produced under specific conditions, allowing the RNA polymerase to transcribe a different set of genes than the housekeeping σ factor, σ70, allows.

Alu elements

Short interspersed DNA elements that are abundant in the human genome.

Apoptosis

Programmed cell death. In contrast to necrosis, which is a form of traumatic cell death that results from acute cellular injury, apoptosis usually confers advantages during an organism's life cycle.

Autophagy

A catabolic process involving the degradation of a cell's own components through the lysosomal machinery. It is a tightly regulated process that plays a normal part in cell growth, development and homeostasis, helping to maintain a balance between the synthesis, degradation and subsequent recycling of cellular products.

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Rikihisa, Y. Anaplasma phagocytophilum and Ehrlichia chaffeensis: subversive manipulators of host cells. Nat Rev Microbiol 8, 328–339 (2010). https://doi.org/10.1038/nrmicro2318

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