Escherichia coli is the predominant facultative anaerobe in the gastrointestinal tracts of mammals. Yet the essence of how E. coli colonizes its mammalian hosts is not understood. According to the nutrient-niche hypothesis, the numerous ecological niches in the intestine are defined by nutrient availability and species coexist by competing for one or a few limiting nutrients. This hypothesis suggests that commensal E. coli strains might act as a first line of defense against enteric E. coli pathogens, but it has not been tested in that light. In this competing renewal application, we propose to extend our investigation of the nutritional basis for intestinal colonization by testing the hypothesis that mucus-derived nutrients provide nutritional niches occupied by competing E. coli commensal and pathogenic strains. The first specific aim will test the hypothesis that different E. coli commensal and pathogenic strains preferentially use different nutrients for colonization of the mouse intestine. Work described in the progress report suggests that different E. coli strains use different nutrients for colonization. For strains representing the four phylogenetic groups of E. coli, the specific nutrient requirements during the initiation and maintenance stages of colonization will be determined by using strategies developed for the currently funded project, i.e., genes induced on DNA arrays under conditions designed to mimic the mouse intestine will be knocked out and the mutants tested in competition with their wildtype parent to determine their relative fitness for colonization. The second specific aim will test the hypothesis that preferential utilization of different nutrients and/or the ability to switch to alternative nutrition is the basis for co-colonization of E. coli strains representing each of the four phylogenetic groups. The corollary hypothesis will also be tested, that direct competition for the same nutrient leads to decreased fitness for colonization of one of the strains. These studies may help explain differences in human susceptibility to infection by E. coli pathogens. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI048945-07
Application #
7071245
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Program Officer
Schmitt, Clare K
Project Start
2000-06-15
Project End
2009-05-31
Budget Start
2006-06-01
Budget End
2007-05-31
Support Year
7
Fiscal Year
2006
Total Cost
$418,855
Indirect Cost
Name
University of Oklahoma Norman
Department
Other Basic Sciences
Type
Schools of Arts and Sciences
DUNS #
848348348
City
Norman
State
OK
Country
United States
Zip Code
73019
Conway, Tyrrell; Cohen, Paul S (2015) Commensal and Pathogenic Escherichia coli Metabolism in the Gut. Microbiol Spectr 3:
Maltby, Rosalie; Leatham-Jensen, Mary P; Gibson, Terri et al. (2013) Nutritional basis for colonization resistance by human commensal Escherichia coli strains HS and Nissle 1917 against E. coli O157:H7 in the mouse intestine. PLoS One 8:e53957
Leatham-Jensen, Mary P; Frimodt-Moller, Jakob; Adediran, Jimmy et al. (2012) The streptomycin-treated mouse intestine selects Escherichia coli envZ missense mutants that interact with dense and diverse intestinal microbiota. Infect Immun 80:1716-27
Maddox, Scott M; Coburn, Phillip S; Shankar, Nathan et al. (2012) Transcriptional regulator PerA influences biofilm-associated, platelet binding, and metabolic gene expression in Enterococcus faecalis. PLoS One 7:e34398
Jones, Shari A; Gibson, Terri; Maltby, Rosalie C et al. (2011) Anaerobic respiration of Escherichia coli in the mouse intestine. Infect Immun 79:4218-26
Fabich, Andrew J; Leatham, Mary P; Grissom, Joe E et al. (2011) Genotype and phenotypes of an intestine-adapted Escherichia coli K-12 mutant selected by animal passage for superior colonization. Infect Immun 79:2430-9
Leatham, Mary P; Banerjee, Swati; Autieri, Steven M et al. (2009) Precolonized human commensal Escherichia coli strains serve as a barrier to E. coli O157:H7 growth in the streptomycin-treated mouse intestine. Infect Immun 77:2876-86
Mercado-Lubo, Regino; Leatham, Mary P; Conway, Tyrrell et al. (2009) Salmonella enterica serovar Typhimurium mutants unable to convert malate to pyruvate and oxaloacetate are avirulent and immunogenic in BALB/c mice. Infect Immun 77:1397-405
Harrington, Susan M; Sheikh, Jalaluddin; Henderson, Ian R et al. (2009) The Pic protease of enteroaggregative Escherichia coli promotes intestinal colonization and growth in the presence of mucin. Infect Immun 77:2465-73
Fabich, Andrew J; Jones, Shari A; Chowdhury, Fatema Z et al. (2008) Comparison of carbon nutrition for pathogenic and commensal Escherichia coli strains in the mouse intestine. Infect Immun 76:1143-52

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