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The Citrobacter rodentium Mouse Model: Studying Pathogen and Host Contributions to Infectious Colitis
Published on: February 19, 2013
Hypervirulent-host-associated Citrobacter rodentium cells have poor acid tolerance
Allen Smith1, Arvind A Bhagwat
1Diet Genomics and Immunology and Laboratory, Henry A. Wallace Beltsville Agricultural Research Center, Agricultural Research Service, USDA, 10300 Baltimore Avenue, BARC-E, Beltsville, MD 20705-2350, USA.
Abstract:
Enhanced virulence or infectivity after passage through a mammalian host has been reported for a number of enteric food-borne pathogens. Citrobacter rodentium is a mouse pathogen that mimics many aspects of enterohemorrhagic Escherichia coli infection of humans and serves as a useful model for studying virulence mechanisms. Emergence of a hyperinfectious state after passage through mouse gastrointestinal tract was reported for C. rodentium. We wanted to investigate if increased acid tolerance could explain hypervirulence status of C. rodentium. Although we were able to observe hyperinfectious state of C. rodentium upon host passage, the cells were extremely acid sensitive. Growth under mildly acidic conditions (LB-MES, pH 5.5) induced acid tolerance of C. rodentium, but did not improve the organism's ability to establish infection. Growth under anaerobic environment on fecal components also did not induce hyperinfectious state. Thus, contrary to conventional anticipation, hypervirulent C. rodentium cells were found to be acid sensitive thereby revealing limitations of the role of mouse gastric acidity by itself in elucidating the hypervirulent phenotype.
Insights
Citrobacter rodentium can become hyperinfectious after passing through mice. However, these hypervirulent cells are surprisingly acid-sensitive, challenging the role of stomach acidity in this phenomenon.
Area of Science:
- Microbiology
- Pathogen Biology
- Infectious Diseases
Background:
- Enteric food-borne pathogens can increase virulence after mammalian host passage.
- Citrobacter rodentium is a mouse model for enterohemorrhagic Escherichia coli infections, known to develop hyperinfectivity.
- The mechanisms underlying C. rodentium hypervirulence require further investigation.
Purpose of the Study:
- To investigate if increased acid tolerance explains the hypervirulent status of C. rodentium after host passage.
- To determine the effect of in vitro acid adaptation and anaerobic growth on fecal components on C. rodentium infectivity.
Main Methods:
- Passaging C. rodentium through a mouse gastrointestinal tract to induce hypervirulence.
- Culturing C. rodentium under mildly acidic conditions (pH 5.5) to assess acid tolerance.
- Evaluating the infectivity of adapted C. rodentium strains in a mouse model.
- Culturing C. rodentium anaerobically on fecal components.
Main Results:
- A hyperinfectious state of C. rodentium was observed after host passage.
- Hypervirulent C. rodentium cells exhibited extreme acid sensitivity.
- Growth in mildly acidic conditions induced acid tolerance but did not enhance infection establishment.
- Anaerobic growth on fecal components did not induce hypervirulence.
Conclusions:
- Hypervirulent C. rodentium is paradoxically acid-sensitive, not acid-tolerant.
- Mouse gastric acidity alone is insufficient to explain the hypervirulent phenotype of C. rodentium.
- Further research is needed to elucidate the factors contributing to C. rodentium hypervirulence.
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