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Pathogenic trickery: deception of host cell processes

Nature Reviews Molecular Cell Biology volume 2, pages 578–588 (2001)Cite this article

Key Points

  • Microbial pathogens have developed numerous sophisticated mechanisms to either block or subvert normal host cellular processes, thereby inadvertently contributing to pathogenesis and disease outcome.

  • Many pathogenic bacteria have evolved mechanisms to engage host cell surface proteins or receptors to initially adhere to, and subsequently invade, host cells. They often achieve this by mimicking host cell ligands. Examples include Listeria spp. and Yersinia spp. invasion of non-phagocytic cells.

  • Bacterial pathogens can also invade cells through lipid rafts, by targeting receptors that are concentrated in these signalling platforms.

  • Some pathogens, including Salmonella spp. and Shigella spp., inject their own proteins into host cells to target the cytoskeleton and signal-transduction pathways. Manipulation of host cell components such as Rho GTPases and the cytoskeleton induces membrane ruffling and allows bacterial invasion.

  • Other pathogens can prevent their own uptake by phagocytic cells. For example, Yersinia spp. and Pseudomonas spp. mediate antiphagocytosis by injecting bacterial proteins into the host cell to disrupt Rho GTPase signalling and the cytoskeleton.

  • Pathogens that remain within a vacuole after bacterial invasion can manipulate host cell vesicular transport and endocytosis. It is likely that this can also be attributed to the actions of translocated bacterial proteins.

  • The study of pathogen–host interactions is contributing to our knowledge of both pathogenic mechanisms and host cell biology.

Abstract

Microbial pathogens cause a spectrum of diseases in humans. Although the disease mechanisms vary considerably, most pathogens have developed virulence factors that interact with host molecules, often usurping normal cellular processes, including cytoskeletal dynamics and vesicle targeting. These virulence factors often mimic host molecules, and mediate events as diverse as bacterial invasion, antiphagocytosis, and intracellular parastism.

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Figure 1: Mechanisms through which bacterial pathogens inhibit phagocytosis.
Figure 2: A common requirement for the Rho subfamily of GTPases in Salmonella-, Shigella- and growth factor-induced membrane ruffling.

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Acknowledgements

We thank members of the Finlay lab for their encouragement. Work in our laboratory is supported by grants from the Canadian Institutes of Health Research (CIHR) and Howard Hughes International Research Scholar Awards to B.B.F.. B.B.F. is a Distinguished Investigator of the CIHR.

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Authors and Affiliations

  1. Biotechnology Laboratory, Room 237-6174 University Boulevard, University of British Columbia, Vancouver, V6T 1Z3, British Columbia, Canada

    Leigh A. Knodler, Jean Celli & B. Brett Finlay

  2. B. Brett Finlay

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  1. Leigh A. Knodler
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Related links

Related links

DATABASE LINKS

Internalin

E-cadherin

InlB

Met tyrosine kinase

C1q

HGF

PI3K

invasin

α3β1

α4β1

α5β1

α6β1

αvβ1

fibronectin

talin

α-actinin

FAK

CAS

Rac1

fimH

CD48

Fcγ-R

CR1

Cdc42

RhoA

YopH

Fyb

SKAP-HOM

Crk

YopE

ExoS

ExoT

Src

IpaA

IpaB

IpaC

IpaD

IpgD

CD44

ezrin

vinculin

cortactin

paxillin

SipA

SopB

SigD

SptP

SifA

Rab7

SpiC

FURTHER INFORMATION

Finlay lab

Salmonella.org

Pathogenic E. coli infection mechanism

Intracellular infection by Salmonella

Theriot lab movie collection

Glossary

PHAGOCYTOSIS

Actin-dependent process, by which cells engulf external particulate material by extension and fusion of pseudopods.

GRAM-POSITIVE BACTERIA

Bacteria with cell walls that retain a basic blue dye during the Gram-stain procedure. These cell walls are relatively thick, consisting of a network of peptidoglycan and lipoteichoic acids.

E-CADHERIN

Calcium-dependent adhesion molecule that mediates homophilic adhesions between epithelial cells.

M CELL

'Membranous' or 'microfold' cell. Specialized cell of follicle-associated epithelium (FAE) in the gut that internalizes macromolecules and microorganisms and delivers them to the underlying lymphoid tissue.

INTEGRINS

A large family of heterodimeric transmembrane proteins that act as receptors for cell-adhesion molecules.

LIPID RAFTS

Dynamic assemblies of cholesterol and sphingolipids in the plasma membrane.

OPSONIZED

Covered with blood-serum proteins — complement, or immunoglobulin-G antibodies — that enhance uptake by phagocytosis.

GPI ANCHOR

A post-translational modification that anchors proteins to membranes, possibly to domains therein. The anchor is made of one molecule of phosphatidylinositol to which a carbohydrate chain is linked through the C-6 hydroxyl of the inositol, and it is linked to the protein through an ethanolamine phosphate moiety.

CAVEOLA

Flask-shaped, cholesterol-rich invagination of the plasma membrane that might mediate the uptake of some extracellular materials, and is probably involved in cell signalling.

GRAM-NEGATIVE BACTERIA

Bacteria with cell walls that do not retain a basic blue dye during the Gram-stain procedure. These cell walls are composed of two membranes, separated by a thin layer of peptidoglycan. The outer membrane anchors surface lipopolysaccharides.

ANTIPHAGOCYTOSIS

Ability of bacteria to inhibit the cytoskeletal rearrangements at the plasma membrane that would lead to their phagocytosis.

DEGRADATIVE ENDOCYTIC PATHWAY

Macromolecules endocytosed at the plasma membrane first arrive in early endosomes, from where they are transported to late endosomes, and finally lysosomes where they are degraded by hydrolases.

GTPASE-ACTIVATING PROTEIN

(GAP). Protein that inactivates small GTP-binding proteins by increasing their rate of GTP hydrolysis.

MACROPINOCYTOSIS

Actin-dependent process by which cells engulf large volumes of fluids.

GUANINE NUCLEOTIDE EXCHANGE FACTOR

(GEF). A protein that facilitates the exchange of GDP (guanine diphosphate) for GTP (guanine triphosphate) in the nucleotide-binding pocket of a GTP-binding protein.

COILING PHAGOCYTOSIS

Internalization of a particle through enclosure by a single finger-like projection that coils around it.

PROMASTIGOTE

Flagellated form of Leishmania carried by an insect vector and injected into the bloodstream of the host.

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Knodler, L., Celli, J. & Finlay, B. Pathogenic trickery: deception of host cell processes. Nat Rev Mol Cell Biol 2, 578–588 (2001). https://doi.org/10.1038/35085062

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