Pretreatment of mice with streptomycin provides a Salmonella enterica serovar Typhimurium colitis model that allows analysis of both pathogen and host

Infect Immun. 2003 May;71(5):2839-58. doi: 10.1128/IAI.71.5.2839-2858.2003.


Salmonella enterica subspecies 1 serovar Typhimurium is a principal cause of human enterocolitis. For unknown reasons, in mice serovar Typhimurium does not provoke intestinal inflammation but rather targets the gut-associated lymphatic tissues and causes a systemic typhoid-like infection. The lack of a suitable murine model has limited the analysis of the pathogenetic mechanisms of intestinal salmonellosis. We describe here how streptomycin-pretreated mice provide a mouse model for serovar Typhimurium colitis. Serovar Typhimurium colitis in streptomycin-pretreated mice resembles many aspects of the human infection, including epithelial ulceration, edema, induction of intercellular adhesion molecule 1, and massive infiltration of PMN/CD18(+) cells. This pathology is strongly dependent on protein translocation via the serovar Typhimurium SPI1 type III secretion system. Using a lymphotoxin beta-receptor knockout mouse strain that lacks all lymph nodes and organized gut-associated lymphatic tissues, we demonstrate that Peyer's patches and mesenteric lymph nodes are dispensable for the initiation of murine serovar Typhimurium colitis. Our results demonstrate that streptomycin-pretreated mice offer a unique infection model that allows for the first time to use mutants of both the pathogen and the host to study the molecular mechanisms of enteric salmonellosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / metabolism
  • Colitis / etiology*
  • Colitis / pathology
  • Disease Models, Animal*
  • Female
  • Intestines / immunology
  • Intestines / microbiology
  • Intestines / pathology
  • Lactobacillus / pathogenicity
  • Lymphoid Tissue / immunology
  • Lymphotoxin beta Receptor
  • Mice
  • Mice, Inbred C57BL
  • Peyer's Patches / physiology
  • Receptors, Tumor Necrosis Factor / physiology
  • Salmonella Infections, Animal / etiology*
  • Salmonella Infections, Animal / pathology
  • Salmonella typhimurium / pathogenicity*
  • Streptomycin / pharmacology*


  • Bacterial Proteins
  • LTBR protein, human
  • Ltbr protein, mouse
  • Lymphotoxin beta Receptor
  • Receptors, Tumor Necrosis Factor
  • Streptomycin