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Vibrio cholerae intestinal population dynamics in the suckling mouse model of infection
M J Angelichio1, J Spector, M K Waldor
1Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
Abstract:
The suckling mouse has been used as a model to identify Vibrio cholerae intestinal colonization factors for over two decades, yet little is known about the location of recoverable organisms along the gastrointestinal (GI) tract following intragastric inoculation. In the present study, we determined the population dynamics of wild-type and avirulent mutant derivatives of both classical and El Tor biotype strains throughout the entire suckling mouse GI tract at various times after intragastric inoculation. Wild-type strains preferentially colonized the middle small bowel with a sharp demarcation between more proximal segments which had manyfold-fewer recoverable cells. Surprisingly, large and stable populations of viable cells were also recovered from the cecum and large bowel. Strains lacking toxin-coregulated pili (TCP(-)) were cleared from the small bowel; however, an El Tor TCP(-) strain colonized the cecum and large bowel almost as well as the wild-type strain. Strains lacking lipopolysaccharide O antigen (OA(-)) were efficiently cleared from the small bowel at early times but then showed net growth for the remainder of the infections. Moreover, large populations of the OA(-) strains were maintained in the large bowel. These results show that for the El Tor biotype neither TCP nor OA is required for colonization of the suckling mouse large bowel. Finally, similar percent recoveries of wild-type, TCP(-), and OA(-) strains from the small bowel at an early time after infection suggest that TCP and OA are not required for strains of either biotype to resist bactericidal mechanisms in the suckling mouse GI tract.
Insights
Vibrio cholerae colonization in suckling mice reveals that while wild-type strains prefer the small bowel, both toxin-coregulated pili (TCP) and lipopolysaccharide O antigen (OA) are not essential for large bowel colonization by the El Tor biotype.
Area of Science:
- Microbiology
- Infectious Diseases
- Gastroenterology
Background:
- The suckling mouse model is crucial for studying Vibrio cholerae intestinal colonization factors.
- Limited understanding exists regarding the distribution of V. cholerae within the gastrointestinal tract post-inoculation.
Purpose of the Study:
- To map the population dynamics of V. cholerae strains throughout the entire suckling mouse GI tract.
- To investigate the roles of toxin-coregulated pili (TCP) and lipopolysaccharide O antigen (OA) in V. cholerae colonization.
Main Methods:
- Intragastric inoculation of suckling mice with wild-type and mutant V. cholerae strains (classical and El Tor biotypes).
- Quantification of recoverable organisms across the full gastrointestinal tract at various time points.
Main Results:
- Wild-type V. cholerae predominantly colonized the middle small bowel, with fewer organisms in proximal segments.
- Significant viable populations of V. cholerae were recovered from the cecum and large bowel.
- TCP-deficient strains were cleared from the small bowel but colonized the large bowel effectively (El Tor biotype).
- OA-deficient strains showed initial clearance from the small bowel followed by growth and substantial recovery in the large bowel.
Conclusions:
- Neither TCP nor OA is required for El Tor biotype V. cholerae to colonize the suckling mouse large bowel.
- Early V. cholerae recovery suggests TCP and OA are not essential for resisting host bactericidal mechanisms in the suckling mouse GI tract.