Abstract

Vitamin B12 is an essential nutrient for humans, that is only synthesized by microbes. Little is known about its biosynthesis or its physiological importance to the microbes that produce it. The bacterium Salmonella typhimurium is capable of a complete synthesis of B12, but does so only under anaerobic conditions. Since sophisticated genetics can be done in this bacterium, we propose a genetic approach to understanding the biosynthesis of vitamin B12 in this organism. We will identify the genes involved (probably an excess of thirty) and will pursue how this pathway is regulated with special emphasis on how 02 is involved. The genetic and biochemical study of enteric bacteria has been done largely under aerobic conditions. Relatively little is known about the details of the anaerobic life-style of these organisms even though virtually all their interactions with human hosts (colonization and pathogenesis) proceed in the absence of oxygen. We suspect that production of B12 anaerobically indicates the existence of a substantial body of metabolic activity that occurs only anaerobically and is totally unknown. We propose to approach these aspects of metabolism by studying the role of B12 in the anaerobic life of Salmonella.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM034804-03
Application #
3286399
Study Section
Microbial Physiology and Genetics Subcommittee 2 (MBC)
Project Start
1985-07-01
Project End
1990-06-30
Budget Start
1987-07-01
Budget End
1988-06-30
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
University of Utah
Department
Type
Schools of Arts and Sciences
DUNS #
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112

  Publications

Anderson, Peter J; Lango, Jozsef; Carkeet, Colleen et al. (2008) One pathway can incorporate either adenine or dimethylbenzimidazole as an alpha-axial ligand of B12 cofactors in Salmonella enterica. J Bacteriol 190:1160-71
Penrod, Joseph T; Roth, John R (2006) Conserving a volatile metabolite: a role for carboxysome-like organelles in Salmonella enterica. J Bacteriol 188:2865-74
Carkeet, Colleen; Dueker, Stephen R; Lango, Jozsef et al. (2006) Human vitamin B12 absorption measurement by accelerator mass spectrometry using specifically labeled (14)C-cobalamin. Proc Natl Acad Sci U S A 103:5694-9
Price-Carter, Marian; Fazzio, Thomas G; Vallbona, Ester Ibanez et al. (2005) Polyphosphate kinase protects Salmonella enterica from weak organic acid stress. J Bacteriol 187:3088-99
Roth, John R; Andersson, Dan I (2004) Amplification-mutagenesis--how growth under selection contributes to the origin of genetic diversity and explains the phenomenon of adaptive mutation. Res Microbiol 155:342-51
Penrod, Joseph T; Mace, Christopher C; Roth, John R (2004) A pH-sensitive function and phenotype: evidence that EutH facilitates diffusion of uncharged ethanolamine in Salmonella enterica. J Bacteriol 186:6885-90
Sheppard, David E; Penrod, Joseph T; Bobik, Thomas et al. (2004) Evidence that a B12-adenosyl transferase is encoded within the ethanolamine operon of Salmonella enterica. J Bacteriol 186:7635-44
Slechta, E Susan; Bunny, Kim L; Kugelberg, Elisabeth et al. (2003) Adaptive mutation: general mutagenesis is not a programmed response to stress but results from rare coamplification of dinB with lac. Proc Natl Acad Sci U S A 100:12847-52
Bunny, Kim; Liu, Jing; Roth, John (2002) Phenotypes of lexA mutations in Salmonella enterica: evidence for a lethal lexA null phenotype due to the Fels-2 prophage. J Bacteriol 184:6235-49
Price-Carter, M; Tingey, J; Bobik, T A et al. (2001) The alternative electron acceptor tetrathionate supports B12-dependent anaerobic growth of Salmonella enterica serovar typhimurium on ethanolamine or 1,2-propanediol. J Bacteriol 183:2463-75

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