Abstract

The object of our proposed research is to gain a better understanding of the genetic and molecular basis of bacterial-host cell interactions. We focus on three aspects of this association: the entry of bacteria (Yersinia and Salmonella) into cultured epithelial cells and macrophages; the analysis of the intercellular and transcytotic pathways followed by these invasive bacteria in well-defined cell culture models; and the interactions of these bacteria in the M cells and Peyer's patches of susceptible and resistant animals. We continue to investigate the genetic and molecular determinants of pathogenicity that permit these microbes to enter cells or to prevent their destruction by cellular and humoral host factors. Our preliminary work in these areas has been most encouraging and suggests that these aspects of microbial pathogenesis are amenable to fruitful experimental investigation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI026195-07
Application #
2063278
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Project Start
1988-04-01
Project End
1998-03-31
Budget Start
1994-04-01
Budget End
1995-03-31
Support Year
7
Fiscal Year
1994
Total Cost
Indirect Cost

  Institution

Name
Stanford University
Department
Microbiology/Immun/Virology
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