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  • Review Article
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Actin-dependent movement of bacterial pathogens

Nature Reviews Microbiology volume 4, pages 91–101 (2006)Cite this article

Key Points

  • Bacteria of the genera Listeria, Rickettsia, Burkholderia, Shigella and Mycobacteria subvert cellular actin dynamics to facilitate their movement within the host cytosol and to infect neighbouring cells while evading host immune surveillance and promoting their intracellular survival. Attaching and effacing (AE) Escherichia coli do not enter host cells but attach intimately to the cell surface, inducing motile actin-rich pedestals, the function of which is unclear.

  • The central role of actin-based motility in bacterial virulence is reflected in the marked attenuation of non-motile mutants of Listeria monocytogenes, Shigella flexneri and Burkholderia pseudomallei. Bacterial factors that control actin assembly are often crucial determinants of virulence and attractive targets for intervention.

  • Analysis of bacterial actin-based motility has revealed novel insights into both pathogen biology and the control of actin assembly in eukaryotic cells. It provides convenient models to study the formation of lamellipodia at the leading edge of motile cells (Listeria and Shigella) and filopodia (Rickettsia).

  • Many of the bacterial factors that are necessary for intracellular motility are expressed at the pole of the bacterium from which the actin-rich tail forms (Listeria ActA, Shigella IcsA and Burkholderia BimA) and are also expressed only to high levels within the host cytosol (Shigella IcsA and Mycobacterium motility factor). In some instances, expression of the bacterial factor has also been shown to be growth-phase dependent (Shigella IcsA).

  • The strategies used by intracellular bacterial pathogens to induce polar actin polymerization, and by AE E. coli to elicit pedestal formation at the plasma membrane, converge on their ability to recruit and activate the cellular Arp2/3 complex. Pathogens that exhibit actin-based movement can be separated into two groups depending on whether they mimic a cellular nucleation-promoting factor (NPF) (Listeria ActA and Rickettsia RickA) or whether they recruit a cellular NPF to the bacterial surface to promote their Arp2/3-mediated motility (Shigella IcsA and AE E. coli Tir).

  • The availability of complete bacterial genome sequences has facilitated identification of new factors that activate actin assembly, including Rickettsia RickA and Burkholderia BimA, and families of homologues of these proteins are emerging in related species that might stimulate actin dynamics in distinct ways.

Abstract

Listeria, Rickettsia, Burkholderia, Shigella and Mycobacterium species subvert cellular actin dynamics to facilitate their movement within the host cytosol and to infect neighbouring cells while evading host immune surveillance and promoting their intracellular survival. 'Attaching and effacing' Escherichia coli do not enter host cells but attach intimately to the cell surface, inducing motile actin-rich pedestals, the function of which is currently unclear. The molecular basis of actin-based motility of these bacterial pathogens reveals novel insights about bacterial pathogenesis and fundamental host-cell pathways.

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Figure 1: Interaction of bacterial pathogens with actin.
Figure 2: Mechanisms of intracellular bacterial actin polymerization.
Figure 3: Actin-based motility of Burkholderia pseudomallei
Figure 4: Mechanisms of actin pedestal formation by enteropathogenic Escherichia coli (EPEC) O127:H6 and enterohaemorrhagic E. coli (EHEC) O157:H7.

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Acknowledgements

The authors gratefully acknowledge the support of the Biotechnology and Biological Sciences Research Council and the Department for the Environment, Food and Rural Affairs.

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Authors and Affiliations

  1. Division of Microbiology, Institute for Animal Health, Compton Laboratory, Berkshire, RG20 7NN, UK

    Joanne M. Stevens, Edouard E. Galyov & Mark P. Stevens

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  1. Joanne M. Stevens
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  2. Edouard E. Galyov
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  3. Mark P. Stevens
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Correspondence to Mark P. Stevens.

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DATABASES

Entrez Genome Project

Burkholderia pseudomallei

Citrobacter rodentium

EHEC O157:H7

Listeria innocua

Listeria monocytogenes

Mycobacterium marinum

Rickettsia conorii

Rickettsia prowazekii

Rickettsia rickettsii

Rickettsia sibirica

Rickettsia typhi

Shigella boydii

Shigella dysenteriae

Shigella flexneri

Streptococcus pneumoniae

FURTHER INFORMATION

The Institute for Animal Health

Glossary

Lamellipodia

Sheet-like protrusions of the plasma membrane associated with exploratory cell movements and cell motility. Composed of orthogonal, highly crosslinked actin arrays. The Rho GTPase Rac has a crucial role in lamellipodia formation through activation of NPFs.

Filopodia

Protrusions of the plasma membrane with finger-like morphology reaching 200 μm in length. Composed of dynamic bundles of actin filaments. Associated with rapid membrane remodelling, transient matrix adhesions and cell motility. Cdc42 has a crucial role in initiating filopodia formation.

Facultative intracellular pathogen

A pathogen that can replicate either within the host cell or as a cell-free unit.

Wiskott–Aldrich syndrome protein

(WASP). The prototypic member of a family of proteins that stimulate the low intrinsic nucleation activity of the Arp2/3 complex.

Src homology-3 (SH3) domain

A small module of ∼50 amino-acid residues found in proteins that interact with proline-rich motifs.

Focal adhesion sites

Adhesions by which cells attach to the underlying substrate. Many structural, cytoskeletal and signalling proteins are concentrated in these structures.

Stress fibres

Contractile filaments involved in the maintenance of cell shape that support the motile apparatus of the cell. At least one end is anchored by a focal adhesion site.

Central and acidic (CA) domain

Forms part of a larger domain called a WCA domain. This region of WASP-family proteins stimulates the Arp2/3 complex.

WASP homology-2 (WH2) domain

WASP homology-2 domain motifs are composed of approximately 35 amino acids and are conserved in cellular proteins that recruit actin monomers.

CAAX motif

A motif that is post-translationally modified by farnesylation at the cysteine residue and that results in localization to the inner leaflet of the plasma membrane.

Type III secretion system

A transmembrane-spanning 'needle complex' involved in the secretion of two classes of proteins, translocators and effectors.

Type V secreted protein

A protein translocated across the outer membrane of Gram-negative bacteria through a transmembrane pore formed by a self-encoded β-barrel structure.

Pleckstrin homology domain

These domains share little sequence conservation but all have a common fold involved in lipid binding and targeting of proteins to the plasma membrane.

CRIB domain

Cdc42/Rac interactive binding (CRIB) domains bind Cdc42 and other Rho-family GTPases.

WAVE

WASP-family verprolin homologous (WAVE)/Scar proteins are members of the WASP family of Arp2/3 activators that lack the domains required for Rho GTPase binding. As such, they are thought to be regulated in a different manner to other WASP-family members.

Adaptor proteins

Proteins involved in signalling cascades that lack any intrinsic enzymatic activities. They mediate protein–protein interactions to form diverse protein complexes.

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Stevens, J., Galyov, E. & Stevens, M. Actin-dependent movement of bacterial pathogens. Nat Rev Microbiol 4, 91–101 (2006). https://doi.org/10.1038/nrmicro1320

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