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Analysis of Salmonella Typhi Pathogenesis in a Humanized Mouse Model.
Stepien, Taylor A; Libby, Stephen J; Karlinsey, Joyce E; Brehm, Michael A; Greiner, Dale L; Shultz, Leonard D; Brabb, Thea; Fang, Ferric C.
Afiliação
  • Stepien TA; Department of Global Health, University of Washington, Seattle, WA, USA.
  • Libby SJ; Department of Laboratory Medicine & Pathology, University of Washington, Seattle, WA, USA.
  • Karlinsey JE; Department of Microbiology, University of Washington, Seattle, WA, USA.
  • Brehm MA; Department of Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
  • Greiner DL; Department of Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
  • Shultz LD; The Jackson Laboratory, Bar Harbor, ME, USA.
  • Brabb T; Department of Comparative Medicine, University of Washington, Seattle, WA, USA.
  • Fang FC; Department of Global Health, University of Washington, Seattle, WA, USA. fcfang@uw.edu.
Methods Mol Biol ; 2427: 215-234, 2022.
Article em En | MEDLINE | ID: mdl-35619037
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.
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Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 3_ND Base de dados: MEDLINE Assunto principal: Salmonella typhi / Febre Tifoide Tipo de estudo: Etiology_studies Limite: Animals Idioma: En Revista: Methods Mol Biol Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 3_ND Base de dados: MEDLINE Assunto principal: Salmonella typhi / Febre Tifoide Tipo de estudo: Etiology_studies Limite: Animals Idioma: En Revista: Methods Mol Biol Ano de publicação: 2022 Tipo de documento: Article