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A complex microworld in the gut: Harnessing pathogen-commensal relations

Nature Medicine volume 18, pages 1190–1191 (2012)Cite this article

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Human infection by diarrheagenic Escherichia coli strains, including enterohemorrhagic (EPEC), enteropathogenic (EHEC), enteroaggregative (EAEC), enteroinvasive (EIEC) and enterotoxigenic (ETEC) E. coli, cause substantial morbidity and mortality worldwide each year1. The most effective way to protect from infection is through primary prevention by improving sanitation and personal hygiene to limit the transmission of bacteria through fecal contamination of food and water supplies. Other measures include eradication of sources of pathogenic bacteria, such as infected cattle, a major source of infection in the developing world. Unfortunately, effective therapies to thwart these water- and food-borne intestinal diseases are lacking. A major factor hampering the development of curative therapies is the poor understanding of how microbial and host factors regulate the colonization and eradication of these deadly bacterial pathogens.

Unlike the harmless commensal E. coli that reside in the human intestine, pathogenic E. coli produces virulence factors and toxins that are crucial for its ability to divide and induce disease. For example, strains of EHEC and EAEC can produce Shiga toxin that contributes to the development of hemolytic uremic syndrome, which is characterized by the triad of acute renal failure, hemolytic anemia and thrombocytopenia. Likewise, ETEC, the most common cause of traveler's diarrhea, produces one or more enterotoxins and fimbriae necessary for attachment to the host intestinal epithelium1. In contrast to EAEC and ETEC, the genomes of EPEC and EHEC harbor the locus of enterocyte effacement (LEE), which is crucial for pathogen colonization and disease pathology2,3. This locus contains a cluster of virulence genes that are crucial for pathogen colonization and include those encoding the type III secretion system (T3SS), a molecular needle-like structure that allows injection of bacterial effector proteins into the host cell cytosol, effector proteins injected via the T3SS, and regulators of epithelial attachment, such as Tir and intimin3.

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Figure 1: Potential therapeutic strategies to treat pathogenic E. coli infection that target pathogen virulence factors and the gut microbiota.

Katie Vicari

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Authors and Affiliations

  1. Nobuhiko Kamada and Gabriel Núñez are in the Department of Pathology, Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan, USA.,

    Nobuhiko Kamada & Gabriel Núñez

  2. Grace Chen is in the Division of Hematology/Oncology, Department of Internal Medicine, Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan, USA.,

    Grace Chen

Authors
  1. Nobuhiko Kamada
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  2. Grace Chen
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Correspondence to Gabriel Núñez.

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Kamada, N., Chen, G. & Núñez, G. A complex microworld in the gut: Harnessing pathogen-commensal relations. Nat Med 18, 1190–1191 (2012). https://doi.org/10.1038/nm.2900

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