Publications by authors named "Tom M Conrad"

Unlabelled: : media-1vid110.1542/5849573989001PEDS-VA_2018-1565 BACKGROUND AND OBJECTIVES: (SA) is the second leading cause of late-onset sepsis among infants in the NICU. Because colonization of nasal mucosa and/or skin frequently precedes invasive infection, decolonization strategies, such as mupirocin application, have been attempted to prevent clinical infection, but data supporting this approach in infants are limited.

View Article and Find Full Text PDF

The complete genome sequences of Mandrillus leucophaeus and Papio ursinus cytomegaloviruses were determined. An isolate from a drill monkey, OCOM6-2, and an isolate from a chacma baboon, OCOM4-52, were subjected to pyrosequencing and assembled. Comparative alignment of published primate cytomegaloviruses (CMVs) showed variable sequence conservation between species.

View Article and Find Full Text PDF

Genetic interaction networks are especially useful for functional assignment of genes and gaining new insights into the systems-level organization of the cell. While studying interactions of nonessential genes can be relatively straight-forward via use of deletion mutants, different approaches must be used to reveal interactions of essential genes due to their indispensability. One method shown to be useful for revealing interactions of essential genes requires tagging the query protein.

View Article and Find Full Text PDF

The initial genome-scale reconstruction of the metabolic network of Escherichia coli K-12 MG1655 was assembled in 2000. It has been updated and periodically released since then based on new and curated genomic and biochemical knowledge. An update has now been built, named iJO1366, which accounts for 1366 genes, 2251 metabolic reactions, and 1136 unique metabolites.

View Article and Find Full Text PDF

Laboratory evolution studies provide fundamental biological insight through direct observation of the evolution process. They not only enable testing of evolutionary theory and principles, but also have applications to metabolic engineering and human health. Genome-scale tools are revolutionizing studies of laboratory evolution by providing complete determination of the genetic basis of adaptation and the changes in the organism's gene expression state.

View Article and Find Full Text PDF

Herein we measure the effect of four adaptive non-synonymous mutations to the glycerol kinase (glpK) gene on catalytic function and regulation, to identify changes that correlate to increased fitness in glycerol media. The mutations significantly reduce affinity for the allosteric inhibitor fructose-1,6-bisphosphate (FBP) and formation of the tetramer, which are structurally related, in a manner that correlates inversely with imparted fitness during growth on glycerol, which strongly suggests that these enzymatic parameters drive growth improvement. Counterintuitively, the glpK mutations also increase glycerol-induced auto-catabolite repression that reduces glpK transcription in a manner that correlates to fitness.

View Article and Find Full Text PDF

Evolution results from molecular-level changes in an organism, thereby producing novel phenotypes and, eventually novel species. However, changes in a single gene can lead to significant changes in biomolecular networks through the gain and loss of many molecular interactions. Thus, significant insights into microbial evolution have been gained through the analysis and comparison of reconstructed metabolic networks.

View Article and Find Full Text PDF

Bacterial survival requires adaptation to different environmental perturbations such as exposure to antibiotics, changes in temperature or oxygen levels, DNA damage, and alternative nutrient sources. During adaptation, bacteria often develop beneficial mutations that confer increased fitness in the new environment. Adaptation to the loss of a major non-essential gene product that cripples growth, however, has not been studied at the whole-genome level.

View Article and Find Full Text PDF

Specific small deletions within the rpoC gene encoding the β'-subunit of RNA polymerase (RNAP) are found repeatedly after adaptation of Escherichia coli K-12 MG1655 to growth in minimal media. Here we present a multiscale analysis of these mutations. At the physiological level, the mutants grow 60% faster than the parent strain and convert the carbon source 15-35% more efficiently to biomass, but grow about 30% slower than the parent strain in rich medium.

View Article and Find Full Text PDF

After hundreds of generations of adaptive evolution at exponential growth, Escherichia coli grows as predicted using flux balance analysis (FBA) on genome-scale metabolic models (GEMs). However, it is not known whether the predicted pathway usage in FBA solutions is consistent with gene and protein expression in the wild-type and evolved strains. Here, we report that >98% of active reactions from FBA optimal growth solutions are supported by transcriptomic and proteomic data.

View Article and Find Full Text PDF

Background: Genome-scale metabolic reconstructions under the Constraint Based Reconstruction and Analysis (COBRA) framework are valuable tools for analyzing the metabolic capabilities of organisms and interpreting experimental data. As the number of such reconstructions and analysis methods increases, there is a greater need for data uniformity and ease of distribution and use.

Description: We describe BiGG, a knowledgebase of Biochemically, Genetically and Genomically structured genome-scale metabolic network reconstructions.

View Article and Find Full Text PDF

Background: Short-term laboratory evolution of bacteria followed by genomic sequencing provides insight into the mechanism of adaptive evolution, such as the number of mutations needed for adaptation, genotype-phenotype relationships, and the reproducibility of adaptive outcomes.

Results: In the present study, we describe the genome sequencing of 11 endpoints of Escherichia coli that underwent 60-day laboratory adaptive evolution under growth rate selection pressure in lactate minimal media. Two to eight mutations were identified per endpoint.

View Article and Find Full Text PDF