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.

Please contact the Joan Staats Library for information regarding this document.

Share

COinS