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  • Review Article
  • Published:

Salmonellae interactions with host processes

Nature Reviews Microbiology volume 13, pages 191–205 (2015)Cite this article

Subjects

Key Points

  • Salmonella spp. deliver effector proteins into host cells to promote replication and survival.

  • Effector proteins that are translocated by the Salmonella pathogenicity island 1 (SPI-1) type III secretion system (T3SS) are important for bacterial invasion into non-phagocytic cells.

  • Effector proteins that are delivered by the SPI-2 T3SS modify the Salmonella-containing vacuole, associated endosomal membranes and associated proteins, all of which promote intracellular replication.

  • Induction of inflammation enhances extracellular growth of salmonellae and enables them to outcompete the gut microbiota.

  • Interplay between the host response pathways of autophagy and pyroptosis is involved in the detection of intracellular Salmonella spp.

  • Distinct functions for many of the Salmonella effector proteins are not fully understood, and it is likely that many of their functions will only be elucidated when their activities are studied in the context of other effectors and are considered in a spatiotemporal context within the host.

Abstract

Salmonellae invasion and intracellular replication within host cells result in a range of diseases, including gastroenteritis, bacteraemia, enteric fever and focal infections. In recent years, considerable progress has been made in our understanding of the molecular mechanisms that salmonellae use to alter host cell physiology; through the delivery of effector proteins with specific activities and through the modulation of defence and stress response pathways. In this Review, we summarize our current knowledge of the complex interplay between bacterial and host factors that leads to inflammation, disease and, in most cases, control of the infection by its animal hosts, with a particular focus on Salmonella enterica subsp. enterica serovar Typhimurium. We also highlight gaps in our knowledge of the contributions of salmonellae and the host to disease pathogenesis, and we suggest future avenues for further study.

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Figure 1: Host pathways manipulated by Salmonella spp. during epithelial cell invasion.
Figure 2: Salmonella-induced inflammation promotes pathogen transmission.
Figure 3: Salmonella spp. manipulation of host membranes.
Figure 4: Activation of autophagy and the inflammasome in response to infection with Salmonella spp.

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Acknowledgements

This work was supported by US National Institutes of Health (NIH) grants RO1 AI030479, RO1 AI048683 and U19 AI090882 to S.I.M.

Author information

Authors and Affiliations

  1. Department of Microbiology, University of Washington, Seattle, 98195, Washington, USA

    Doris L. LaRock, Anu Chaudhary & Samuel I. Miller

  2. Department of Genome Sciences, University of Washington, Seattle, 98195, Washington, USA

    Samuel I. Miller

  3. Department of Immunology, University of Washington, Seattle, 98195, Washington, USA

    Samuel I. Miller

  4. Department of Medicine, University of Washington, Seattle, 98195, Washington, USA

    Samuel I. Miller

Authors
  1. Doris L. LaRock
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  2. Anu Chaudhary
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  3. Samuel I. Miller
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Correspondence to Samuel I. Miller.

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Supplementary information

Supplementary information S1 (table)

Effectors of the Salmonella spp. T3SSs. (PDF 269 kb)

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Glossary

Microfold cells

(M cells). Specialized epithelial cells that phagocytose molecules in the intestinal lumen for transepithelial transport to enable immunological sampling of antigens.

Peyer's patches

Organized lymphoid regions of the small intestine monolayer that function in immune surveillance and the generation of a localized immune response.

Type III secretion systems

(T3SSs). Needle-like apparatuses that are assembled by pathogenic bacteria for the delivery of bacterial effectors directly into host cells.

Pathogenicity island

A large horizontally acquired region of genomic DNA that often encodes virulence factors.

Macropinocytosis

A non-selective form of endocytosis that involves membrane ruffling.

Autophagy

A catabolic cellular process in which cytoplasmic contents, such as damaged organelles and proteins, are targeted for lysosomal degradation.

RHO GTPases

A family of GTPases that are important molecular switches for regulating actin dynamics.

Tight junctions

The adhesive contacts comprising protein complexes that function to limit the movement of molecules and ions through the space between cells in a monolayer.

Toll-like receptors

(TLRs). Membrane-bound receptors of the innate immune system that recognize specific pathogen-associated molecular patterns.

Caspase

A family of cysteine proteases that have an essential role in cell death pathways.

Stromal cells

Connective tissue cells that include enterocytes, tissue fibroblasts and vascular endothelial cells.

Endocytosis

The process by which extracellular particles are engulfed by eukaryotic cells and enclosed in a vesicle.

Siderophore

A small molecule that has a high affinity for iron and is secreted by bacteria to scavenge this element.

Reactive oxygen species

(ROS). Chemically reactive species that contain oxygen. They are produced as a by-product of aerobic respiration and function in combating microbial infections.

Microtubular network

The dynamic network of tubulin polymers that constitute an important component of the cell cytoskeleton. This network is used for intracellular transport, including movement of secretory vesicles and organelles such as the Salmonella-containing vacuole.

Sorting nexin

A family of proteins characterized by the presence of a phox-homology domain that functions by binding to phosphatidylinositol-3- monophosphate. Sorting nexins associate with the endocytic network and are involved in endocytosis, endosomal sorting and endosomal signalling.

Periphery-directed transport vesicles

Vesicles, such as those from the Salmonella-containing vacuole, that move towards the periphery of cells along microtubules.

Prenylation

The attachment of farnesyl or geranyl–geranyl groups to carboxy-terminal cysteine residues that are present in specific prenylation motifs of proteins, which promotes membrane association or protein–protein interactions.

S-palmitoylated

The reversible covalent post-translational attachment of lipids (usually palmitate) to cysteine residues of proteins.

Peroxisomes

Organelles that degrade long-chain fatty acids in eukaryotes.

Pattern recognition receptors

(PRRs). Proteins of the innate immune system that recognize pathogen-associated molecular patterns and initiate an innate immune response that facilitates pathogen clearance by triggering cytokine and chemokine expression.

NOD-like receptors

(NLRs). Intracellular receptors of the innate immune system that recognize pathogen- associated molecular patterns.

Pyroptosis

An inflammatory, programmed cell death pathway that is triggered by the activation of caspase 1 and caspase 11 in mice, and by caspase 4, caspase 5 and caspase 11 in humans.

Endotoxic shock

A severe inflammatory reaction that is induced by high levels of endotoxin (lipopolysaccharide) in the bloodstream.

Mitophagy

The process of targeting mitochondria for autophagic degradation.

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LaRock, D., Chaudhary, A. & Miller, S. Salmonellae interactions with host processes. Nat Rev Microbiol 13, 191–205 (2015). https://doi.org/10.1038/nrmicro3420

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