Research Article: A novel mouse model of Campylobacter jejuni enteropathy and diarrhea

Date Published: May 23, 2018

Publisher: Public Library of Science

Author(s): Natasa Giallourou, Gregory L. Medlock, David T. Bolick, Pedro HQS Medeiros, Solanka E. Ledwaba, Glynis L. Kolling, Kenneth Tung, Patricia Guerry, Jonathan R. Swann, Richard L. Guerrant, Andreas J. Baumler.


Campylobacter infections are among the leading bacterial causes of diarrhea and of ‘environmental enteropathy’ (EE) and growth failure worldwide. However, the lack of an inexpensive small animal model of enteric disease with Campylobacter has been a major limitation for understanding its pathogenesis, interventions or vaccine development. We describe a robust standard mouse model that can exhibit reproducible bloody diarrhea or growth failure, depending on the zinc or protein deficient diet and on antibiotic alteration of normal microbiota prior to infection. Zinc deficiency and the use of antibiotics create a niche for Campylobacter infection to establish by narrowing the metabolic flexibility of these mice for pathogen clearance and by promoting intestinal and systemic inflammation. Several biomarkers and intestinal pathology in this model also mimic those seen in human disease. This model provides a novel tool to test specific hypotheses regarding disease pathogenesis as well as vaccine development that is currently in progress.

Partial Text

Campylobacter jejuni is a Gram-negative helical or rod shaped bacteria that is a common cause of gastroenteritis. C. jejuni is one of the leading recognized bacterial causes of food-borne illnesses in the U.S. and worldwide [1, 2].

Given the increasingly recognized importance of Campylobacter infections (as causes of severe bloody diarrhea or growth failure in children living in developing areas) and of food and milk-borne outbreaks in developed areas, not to mention the troubling sequelae like Guillain-Barré Syndrome (GBS), the need for improved understanding of its pathogenesis and effective interventions or vaccines is paramount. A major limitation of work in this area is the lack of an inexpensive animal model that mimics human disease. Here, we demonstrate that nutritional and antimicrobial manipulations can enable us to model growth failure or overt bloody diarrhea. With manipulation of the antibiotics or diet, we may be able to model weight loss without overt diarrhea (as suggested by the transient effects of Campylobacter without antibiotic pretreatment shown in Fig 1A). This model opens tremendous opportunities to help enable vaccine development or other potential interventions.