Salmonellosis is one of the most common causes of acute gastroenteritis. During this infection, Salmonella enters its host preferentially through the Peyer's patches of the terminal ileum. The Peyer's patches also serve as main port of entry during typhoid fever, a disease caused Salmonella typhi in humans. The lpf operon encodes long polar fimbriae (LP fimbriae), which allow Salmonella typhimurium to adhere to murine Peyer's patches and are necessary for destruction of M cells. Fimbrial adhesins have very specific structural requirements for recognition of epithelial surface epitopes, thereby restricting bacterial binding to cell populations carrying the optimal receptor epitope. This is referred to as tropism and partly determines the niche a pathogen is able to occupy. The long term objective of this study is to understand the mechanisms which contribute to the tissue tropism of S. typhimurium for Peyer's patches. The study of binding properties of the adhesin encoded by the lpf operon and the identification of the cell type it binds in the epithelium of murine Peyer's patches are the main focus of this research.
The aims of this research are: (I) To gain insight as to how LP fimbriae bind to murine Peyer's patches, the subunit of LP fimbriae mediating adhesion will be identified and its binding properties will be studied in vitro and in vivo. (II) To increase our understanding of how S. typhimurium adheres to the surface of Peyer's patches, the cell type to which LP fimbriae bind in the follicle associated epithelium will be identified. In particular, Dr. Baumler will investigate whether the lpf fimbrial operon of S. typhimurium mediates binding to M cells or a different target in Payer's patches. S. typhimurium is both an important human pathogen and the basis for live attenuated vaccine carrier strains. This study will provide knowledge about the tropism of S. typhimurium for gut associated lymphoid tissue, which is of value for both areas of research. The investigator's results will therefore facilitate both the design of improved attenuated vaccines and the development of new strategies to prevent disease caused by this pathogen. Understanding of the tissue tropism of S. typhimurium in the intestine will in addition provide fascinating new insights into how this and other enteroinvasive pathogens cause disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29AI040124-04
Application #
6170108
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Program Officer
Hamilton, Frank A
Project Start
1997-05-01
Project End
2002-04-30
Budget Start
2000-05-01
Budget End
2001-04-30
Support Year
4
Fiscal Year
2000
Total Cost
$102,646
Indirect Cost
Name
Texas A&M University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
City
College Station
State
TX
Country
United States
Zip Code
77845
Bäumler, Andreas; Fang, Ferric C (2013) Host specificity of bacterial pathogens. Cold Spring Harb Perspect Med 3:a010041
Sterzenbach, Torsten; Nguyen, Kim T; Nuccio, Sean-Paul et al. (2013) A novel CsrA titration mechanism regulates fimbrial gene expression in Salmonella typhimurium. EMBO J 32:2872-83
Chu, Hiutung; Pazgier, Marzena; Jung, Grace et al. (2012) Human ?-defensin 6 promotes mucosal innate immunity through self-assembled peptide nanonets. Science 337:477-81
Wangdi, Tamding; Winter, Sebastian E; Baumler, Andreas J (2012) Typhoid fever: ""you can't hit what you can't see"". Gut Microbes 3:88-92
Thiennimitr, Parameth; Winter, Sebastian E; Baumler, Andreas J (2012) Salmonella, the host and its microbiota. Curr Opin Microbiol 15:108-14
Santos, R L; Almeida, A P; Xavier, M N et al. (2011) Enteric pathology and Salmonella-induced cell death in healthy and SIV-infected rhesus macaques. Vet Pathol 48:933-41
Winter, Sebastian E; Baumler, Andreas J (2011) A breathtaking feat: to compete with the gut microbiota, Salmonella drives its host to provide a respiratory electron acceptor. Gut Microbes 2:58-60
Adams, L Garry; Khare, Sangeeta; Lawhon, Sara D et al. (2011) Enhancing the role of veterinary vaccines reducing zoonotic diseases of humans: linking systems biology with vaccine development. Vaccine 29:7197-206
Keestra, A Marijke; Godinez, Ivan; Xavier, Mariana N et al. (2011) Early MyD88-dependent induction of interleukin-17A expression during Salmonella colitis. Infect Immun 79:3131-40
Keestra, A Marijke; Winter, Maria G; Klein-Douwel, Daisy et al. (2011) A Salmonella virulence factor activates the NOD1/NOD2 signaling pathway. MBio 2:

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