Abstract

The object of the research proposed here is to gain a better understanding of both the genetic and molecular basis of the interaction of enteric microorganisms with epithelial cells. We have focused on three aspects of this interaction: entry of the bacteria (Yersinia and Salmonella) into epithelial cells; replication of the bacteria within the epithelial cell; and transcytosis of the bacteria through the epithelial cell. We will continue to characterize the invasion determinants, inv and ail, of Yersinia both genetically and biochemically. In vitro modified inv and ail genes will be returned to Yersinia to better assess the role these determinants play in the virulence of this organism. In addition, we will extend our studies with Salmonella to identify and characterize the genes (and their products) involved in invasion and intracellular replication. Our preliminary work in these areas has been most encouraging and indicates these aspects of microbial pathogenesis are amenable to experimental investigation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI026195-03
Application #
3139912
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Project Start
1988-04-01
Project End
1993-03-31
Budget Start
1990-04-01
Budget End
1991-03-31
Support Year
3
Fiscal Year
1990
Total Cost
Indirect Cost

  Institution

Name
Stanford University
Department
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305

  Publications

Blaser, Martin J; Falkow, Stanley (2009) What are the consequences of the disappearing human microbiota? Nat Rev Microbiol 7:887-94
Lawley, Trevor D; Bouley, Donna M; Hoy, Yana E et al. (2008) Host transmission of Salmonella enterica serovar Typhimurium is controlled by virulence factors and indigenous intestinal microbiota. Infect Immun 76:403-16
Lawley, Trevor D; Chan, Kaman; Thompson, Lucinda J et al. (2006) Genome-wide screen for Salmonella genes required for long-term systemic infection of the mouse. PLoS Pathog 2:e11
Chan, Kaman; Kim, Charles C; Falkow, Stanley (2005) Microarray-based detection of Salmonella enterica serovar Typhimurium transposon mutants that cannot survive in macrophages and mice. Infect Immun 73:5438-49
Darby, Creg; Ananth, Sandya L; Tan, Li et al. (2005) Identification of gmhA, a Yersinia pestis gene required for flea blockage, by using a Caenorhabditis elegans biofilm system. Infect Immun 73:7236-42
Brodsky, Igor E; Ghori, Nafisa; Falkow, Stanley et al. (2005) Mig-14 is an inner membrane-associated protein that promotes Salmonella typhimurium resistance to CRAMP, survival within activated macrophages and persistent infection. Mol Microbiol 55:954-72
De Keersmaecker, Sigrid C J; Marchal, Kathleen; Verhoeven, Tine L A et al. (2005) Microarray analysis and motif detection reveal new targets of the Salmonella enterica serovar Typhimurium HilA regulatory protein, including hilA itself. J Bacteriol 187:4381-91
Prouty, A M; Brodsky, I E; Manos, J et al. (2004) Transcriptional regulation of Salmonella enterica serovar Typhimurium genes by bile. FEMS Immunol Med Microbiol 41:177-85
Kim, Charles C; Falkow, Stanley (2004) Delineation of upstream signaling events in the salmonella pathogenicity island 2 transcriptional activation pathway. J Bacteriol 186:4694-704
Prouty, A M; Brodsky, I E; Falkow, S et al. (2004) Bile-salt-mediated induction of antimicrobial and bile resistance in Salmonella typhimurium. Microbiology 150:775-83

Showing the most recent 10 out of 79 publications