Affiliation:
1. Michael Smith Laboratories and Department of Microbiology and Immunology
2. Department of Anatomical Pathology, Vancouver General Hospital, Vancouver, Canada
3. BC Research Institute, BC Children's and Women's Hospital, Vancouver, Canada
4. Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, Canada
Abstract
ABSTRACT
Salmonella
species cause a wide range of disease in multiple hosts.
Salmonella enterica
serovar Typhimurium causes self-limited intestinal disease in humans and systemic typhoid-like illness in susceptible mice. The prevailing dogma in murine
S. enterica
serovar Typhimurium pathogenesis is that distinct virulence mechanisms—
Salmonella
pathogenicity islands 1 and 2 (SPI1 and SPI2)—perform distinct roles in pathogenesis, the former being important for invasion and intestinal disease and the latter important for intracellular survival and systemic persistence and disease. Although evidence from bovine infections has suggested that SPI2 has a role in ileal disease, there is no evidence that SPI2 is important for inflammation in a disease that more closely recapitulates human colitis. Using
S. enterica
serovar Typhimurium strains that lack functional type III secretion systems, we demonstrate that SPI2 is essential for complete virulence in murine infectious enterocolitis. Using a recently characterized murine model (M. Barthel,S. Hapfelmeier, L. Quintanilla-Martinez, M. Kremer, M. Rohde, M. Hogardt, K. Pfeffer, H. Russmann, and W. D. Hardt, Infect. Immun.
71:
2839-2858, 2003), we demonstrate that SPI1 mutants are unable to cause intestinal disease 48 h after infection and that SPI2-deficient bacteria also cause significantly attenuated typhlitis. We show that at the peak of inflammation in the cecum, SPI2 mutants induce diminished intercellular adhesion molecule 1 expression and neutrophil recruitment but that wild-type and mutant
Salmonella
are similarly distributed in the lumen of the infected organ. Finally, we demonstrate that attenuation of intestinal inflammation is accompanied by resolution of typhlitis in the mutant, but not wild-type, infections. Collectively, these results indicate that SPI2 is needed for enterocolitis, as well as for systemic disease.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
169 articles.
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