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Cells within cells: Rickettsiales and the obligate intracellular bacterial lifestyle

Abstract

The Rickettsiales are a group of obligate intracellular vector-borne Gram-negative bacteria that include many organisms of clinical and agricultural importance, including Anaplasma spp., Ehrlichia chaffeensis, Wolbachia, Rickettsia spp. and Orientia tsutsugamushi. This Review provides an overview of the current state of knowledge of the biology of these bacteria and their interactions with host cells, with a focus on pathogenic species or those that are otherwise important for human health. This includes a description of rickettsial genomics, bacterial cell biology, the intracellular lifestyles of Rickettsiales and the mechanisms by which they induce and evade the innate immune response.

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Fig. 1: Phylogenetic tree showing relationship between selected Rickettsiales species as determined by 16S sequences.
Fig. 2: Overview of the intracellular life cycles of Rickettsiales.
Fig. 3: Attachment and invasion of Rickettsiales species into mammalian cells.
Fig. 4: Evasion of cellular innate immunity by Rickettsiales.

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Acknowledgements

The author apologizes to colleagues whose work could not be cited due to space limitations. J.S. is grateful to the reviewers for their time and effort in carefully reviewing the manuscript, and to past and current laboratory members for scientific contributions. J.S. was funded by a Dorothy Hodgkin Fellowship from the Royal Society and by National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID) grant 1R21AI144385-01A1.

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Glossary

Chlamydiales

An order of obligate intracellular bacteria that live in animals, insects and protozoa and includes species that are pathogenic to humans.

Endosymbiont

An organism that lives within another organism, either intracellularly or extracellularly, usually but not always in a mutually beneficial symbiosis.

Eschar

A small mark on the skin that resembles a cigarette burn and that forms at the site of infection by Orientia tsutsugamushi and some spotted fever group rickettsiae.

Pseudogenization

An evolutionary process in which a gene loses its function through mutation or disruption of the coding sequence.

Peptidoglycan

A highly cross-linked polymer composed of a polysaccharide backbone and short peptide sidechains that encases bacterial cells and confers osmotic protection and rigidity.

Lipopolysaccharide

(LPS). A large, negatively charged, lipid-anchored polysaccharide that comprises the outer leaflet of the outer membrane of most Gram-negative bacteria.

RecF-mediated gene conversion

A pathway of homologous recombination that repairs double-stranded breaks in bacteria.

Autotransporter family proteins

A family of outer membrane proteins that are widespread in pathogenic bacteria and are composed of a transmembrane β-barrel domain and a soluble extracellular passenger domain, which is sometimes cleaved and secreted into the extracellular space.

PDZ domains

Common structural domains of 80–90 amino acids found in proteins in both prokaryotes and eukaryotes.

Two-component systems

Signalling systems common in bacteria, typically comprising a histidine kinase sensor protein and a corresponding response regulator.

Endocytosis

A process by which eukaryotic cells internalize extracellular material that includes phagocytosis, pinocytosis and receptor-mediated endocytosis.

Filopodia

Thin, actin-rich membrane protrusions that extend from the edge of eukaryotic cells and play a role in sensing the environment, cell migration and cell–cell interactions.

Ankyrin repeat-containing proteins

(Ank proteins). A large family of mostly eukaryotic proteins that contain 1–34 copies of an Ankyrin repeat of ~33 amino acids, present in pathogenic bacteria and viruses.

Tetratricopeptide repeat proteins

(TPR). A family of proteins containing a repeat of 34 amino acids arrayed in a tandem of 3–16 motifs, present in both prokaryotic and eukaryotic organisms.

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Salje, J. Cells within cells: Rickettsiales and the obligate intracellular bacterial lifestyle. Nat Rev Microbiol 19, 375–390 (2021). https://doi.org/10.1038/s41579-020-00507-2

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