Analysis of Salmonella Typhi Pathogenesis in a Humanized Mouse Model.
Document Type
Article
Publication Date
2022
Publication Title
Methods in molecular biology (Clifton, N.J.)
Keywords
JMG, Animals, Disease Models, Animal, Mice, Mice, SCID, Salmonella typhi, Typhoid Fever, Virulence
JAX Source
Methods Mol Biol 2022; 2427:215-234
Volume
2427
First Page
215
Last Page
234
ISSN
1940-6029
PMID
35619037
DOI
https://doi.org/10.1007/978-1-0716-1971-1_18
Abstract
Efforts to understand molecular mechanisms of pathogenesis of the human-restricted pathogen Salmonella enterica serovar Typhi, the causative agent of typhoid fever, have been hampered by the lack of a tractable small animal model. This obstacle has been surmounted by a humanized mouse model in which genetically modified mice are engrafted with purified CD34+ stem cells from human umbilical cord blood, designated CD34+ Hu-NSG (formerly hu-SRC-SCID) mice. We have shown that these mice develop a lethal systemic infection with S. Typhi that is dependent on the presence of engrafted human hematopoietic cells. Immunological and pathological features of human typhoid are recapitulated in this model, which has been successfully employed for the identification of bacterial genetic determinants of S. Typhi virulence. Here we describe the methods used to infect CD34+ Hu-NSG mice with S. Typhi in humanized mice and to construct and analyze a transposon-directed insertion site sequencing S. Typhi library, and provide general considerations for the use of humanized mice for the study of a human-restricted pathogen.
Recommended Citation
Stepien T,
Libby S,
Karlinsey J,
Brehm M,
Greiner D,
Shultz LD,
Brabb T,
Fang F.
Analysis of Salmonella Typhi Pathogenesis in a Humanized Mouse Model. Methods Mol Biol 2022; 2427:215-234