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From bench to bedside: stealth of enteroinvasive pathogens

Nature Reviews Microbiology volume 6, pages 883–892 (2008)Cite this article

Key Points

  • This article discusses recent advances in our understanding of the molecular basis of host–pathogen interactions that help explain the clinical presentation and pathology of the enteric fever syndrome.

  • Approaches to the integration of molecular bacterial pathogenesis research and the clinical presentation of infectious diseases are illustrated by discussing the pathogenesis of typhoid fever, brucellosis and yersiniosis.

  • The article focuses on virulence strategies that are shared by pathogens which cause enteric fever and how these strategies could help explain similarities in host responses and the disease outcome.

  • Recent research indicates that bacteria associated with enteric fever alter their 'bar code' to conceal their identity from the host, resulting in a clinical presentation that is difficult to distinguish from viral or parasitic infections.

Abstract

Bacterial enteric infections are often associated with diarrhoea or vomiting, which are clinical presentations commonly referred to as gastroenteritis. However, some enteric pathogens, including typhoidal Salmonella serotypes, Brucella species and enteropathogenic Yersinia species are associated with a clinical syndrome that is characterized by abdominal pain and/or fever and is distinct from acute gastroenteritis. Recent insights into molecular mechanisms of the host–pathogen interaction show that these enteric pathogens share important characteristics that explain why the initial host responses associated with these agents more closely resemble host responses to viral or parasitic infections. Host responses contribute to the clinical presentation of disease and improved understanding of these responses in the laboratory is beginning to bridge the gap between bench and bedside.

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Figure 1: Major syndromes of enteric infection.
Figure 2: Comparison of host responses elicited in patients with bacteraemia.
Figure 3: Function of the viaB locus in Vi-capsule biosynthesis and evasion of detection by TLR4 and TLR5.
Figure 4: Lipid A structures of Salmonella serovars, Brucella species and Yersinia species.

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Acknowledgements

This work was supported by Public Health Service grants AI050553 (to R.M.T.), AI067676 (to G.M.Y.), AI042081 (to J.V.S.), and AI040124, AI044170 and AI079173 (to A.J.B.).

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  1. Department of Food Science and Technology, College of Agricultural & Environmental Sciences, University of California at Davis, One Shields Avenue, Davis, 9561 6 California, USA.

Authors and Affiliations

  1. Department of Medical Microbiology and Immunology, School of Medicine,

    Renée M. Tsolis, Glenn M. Young, Jay V. Solnick & Andreas J. Bäumler

Authors
  1. Renée M. Tsolis
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  2. Glenn M. Young
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  3. Jay V. Solnick
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  4. Andreas J. Bäumler
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Correspondence to Andreas J. Bäumler.

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DATABASES

Entrez Genome Project

Brucella abortus

Corynebacterium diphteriae

Escherichia coli

S. Enteritidis

S. Typhi

S. Typhimurium

Vibrio cholerae

Yersinia enterocolitica

Yersinia pestis

Yersinia pseudotuberculosis

Entrez Protein

IFN

IL-1β

IL-6

TLR1

TLR2

TLR3

TLR4

TLR5

TLR6

TLR7

TLR8

TNF-α

FURTHER INFORMATION

Andreas J. Bäumler's homepage

Glossary

Lamina propria

Connective tissue that underlies the epithelium of mucosal surfaces.

Pattern-recognition receptor

A receptor of the innate immune-surveillance system that recognizes and responds to conserved microorganism-associated molecular patterns.

Reactive microscopic pattern

Microscopic pathological changes in tissue.

Exudative inflammation

Reactive microscopic pattern characterized by acutely increased vascular permeability, neutrophil recruitment and the formation of tissue exudates above surfaces or within spaces.

Pyogenic bacteria

Pus-forming bacteria that are associated with exudative inflammation and neutrophil recruitment.

Pyrogenic cytokine

A fever-inducing cytokine, including interleukin-1 (IL-1), IL-6, tumour necrosis factor-α and interferon.

Interstitial inflammation

Reactive microscopic pattern characterized by inflammatory infiltrates that are dominated by macrophages, dendritic cells and/or lymphocytes.

Atypical bacteria

Bacteria that differ from pyogenic bacteria, in that they do not elicit neutrophil recruitment during infection.

Neutrophilia

Increased counts of neutrophils in the blood.

Intravascular coagulopathy

Formation of blood clots in blood vessels owing to activation of the clotting cascade.

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Tsolis, R., Young, G., Solnick, J. et al. From bench to bedside: stealth of enteroinvasive pathogens. Nat Rev Microbiol 6, 883–892 (2008). https://doi.org/10.1038/nrmicro2012

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