To colonize an animal host, bacteria must acquire nutrients for growth. However, despite extensive research, next to nothing is known about the nutrients and metabolic pathways used in situ by the 400-500 species which inhabit the mammalian large intestine. The proposed research uses functional genomics technology to investigate the acquisition of nutrients by enteric bacteria during the colonization process. Specifically, we will test the hypothesis that induction of the pathways used for catabolism of mucus-derived sugars is essential for colonization of E. coli. Global transcription assays will be used to identify regulons induced for growth on the complex mixture of nutrients present in intestinal mucus. Probes prepared from cells grown on minimal media containing cecal mucus will be hybridized to DNA arrays of all E. coli genes. Pathways induced in situ for growth on mucus will be identified by analyzing global transcription patterns of E. coli cells in the ceca of experimentally colonized germ-free mice. Pathways which contribute to the ability of E. coli to successfully compete with the 400-500 other species in the large intestine will be examined. Mutant strains selectively blocked in specific catabolic pathways will be tested for their ability to colonize mice and green fluorescent protein reporter fusions will be used to determine the temporal and spatial expression of these regulons in individual bacterial cells during colonization. These experiments will identify the distinct physiological roles of individual mucosal sugars in colonization of the large intestine by E. coli, providing knowledge important for addressing the more general question of whether or not metabolic diversity allows pathogenic E. coli strains to colonize in the presence of precolonized strains, thus leading to their ability to cause disease. Knowing precisely which nutrients are essential for colonization should lead to improved strategies for combating infection.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI048945-03
Application #
6511424
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Program Officer
Schmitt, Clare K
Project Start
2000-06-15
Project End
2004-05-31
Budget Start
2002-06-01
Budget End
2003-05-31
Support Year
3
Fiscal Year
2002
Total Cost
$337,335
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
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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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