8 results on '"Peterson, Scott"'
Search Results
2. LUD, a new protein domain associated with lactate utilization.
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Hwang, William C., Bakolitsa, Constantina, Punta, Marco, Coggill, Penelope C., Bateman, Alex, Axelrod, Herbert L., Rawlings, Neil D., Sedova, Mayya, Peterson, Scott N., Eberhardt, Ruth Y., Aravind, L., Pascual, Jaime, and Godzik, Adam
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PROTEINS ,LACTATES ,CRYSTAL structure ,DEINOCOCCUS radiodurans ,COFACTORS (Biochemistry) ,ENTEROTYPES - Abstract
Background A novel highly conserved protein domain, DUF162 [Pfam: PF02589], can be mapped to two proteins: LutB and LutC. Both proteins are encoded by a highly conserved LutABC operon, which has been implicated in lactate utilization in bacteria. Based on our analysis of its sequence, structure, and recent experimental evidence reported by other groups, we hereby redefine DUF162 as the LUD domain family. Results JCSG solved the first crystal structure [PDB:2G40] from the LUD domain family: LutC protein, encoded by ORF DR-1909, of Deinococcus radiodurans. LutC shares features with domains in the functionally diverse ISOCOT superfamily. We have observed that the LUD domain has an increased abundance in the human gut microbiome. Conclusions We propose a model for the substrate and cofactor binding and regulation in LUD domain. The significance of LUD-containing proteins in the human gut microbiome, and the implication of lactate metabolism in the radiation-resistance of Deinococcus radiodurans are discussed. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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3. The auxiliary protein complex SaePQ activates the phosphatase activity of sensor kinase SaeS in the SaeRS two-component system of Staphylococcus aureus.
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Jeong, Do-Won, Cho, Hoonsik, Jones, Marcus B., Shatzkes, Kenneth, Sun, Fei, Ji, Quanjiang, Liu, Qian, Peterson, Scott N., He, Chuan, and Bae, Taeok
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DEPHOSPHORYLATION ,STAPHYLOCOCCUS aureus ,PROTEINS ,PHOSPHATASES ,HEMOLYSIS & hemolysins ,GENE expression - Abstract
In bacterial two-component regulatory systems ( TCSs), dephosphorylation of phosphorylated response regulators is essential for resetting the activated systems to the pre-activation state. However, in the SaeRS TCS, a major virulence TCS of Staphylococcus aureus, the mechanism for dephosphorylation of the response regulator SaeR has not been identified. Here we report that two auxiliary proteins from the sae operon, SaeP and SaeQ, form a protein complex with the sensor kinase SaeS and activate the sensor kinase's phosphatase activity. Efficient activation of the phosphatase activity required the presence of both SaeP and SaeQ. When SaeP and SaeQ were ectopically expressed, the expression of coagulase, a sae target with low affinity for phosphorylated SaeR, was greatly reduced, while the expression of alpha-haemolysin, a sae target with high affinity for phosphorylated SaeR, was not, demonstrating a differential effect of SaePQ on sae target gene expression. When expression of SaePQ was abolished, most sae target genes were induced at an elevated level. Since the expression of SaeP and SaeQ is induced by the SaeRS TCS, these results suggest that the SaeRS TCS returns to the pre-activation state by a negative feedback mechanism. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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4. Characterizing the Escherichia coli O157:H7 Proteome Including Protein Associations with Higher Order Assemblies.
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Pieper, Rembert, Quanshun Zhang, Clark, David J., Shih-Ting Huang, Moo-Jin Suh, Braisted, John C., Payne, Samuel H., Fleischmann, Robert D., Peterson, Scott N., and Tzipori, Saul
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ESCHERICHIA coli ,PROTEINS ,GENETIC transformation ,MEDICAL research ,MEDICAL sciences - Abstract
Background: The recent outbreak of severe infections with Shiga toxin (Stx) producing Escherichia coli (STEC) serotype O104:H4 highlights the need to understand horizontal gene transfer among E. coli strains, identify novel virulence factors and elucidate their pathogenesis. Quantitative shotgun proteomics can contribute to such objectives, allowing insights into the part of the genome translated into proteins and the connectivity of biochemical pathways and higher order assemblies of proteins at the subcellular level. Methodology/Principal Findings: We examined protein profiles in cell lysate fractions of STEC strain 86-24 (serotype O157:H7), following growth in cell culture or bacterial isolation from intestines of infected piglets, in the context of functionally and structurally characterized biochemical pathways of E. coli. Protein solubilization in the presence of Triton X-100, EDTA and high salt was followed by size exclusion chromatography into the approximate M
r ranges greater than 280 kDa, 280-80 kDa and 80-10 kDa. Peptide mixtures resulting from these and the insoluble fraction were analyzed by quantitative 2D-LC-nESI-MS/MS. Of the 2521 proteins identified at a 1% false discovery rate, representing 47% of all predicted E. coli O157:H7 gene products, the majority of integral membrane proteins were enriched in the high Mr fraction. Hundreds of proteins were enriched in a Mr range higher than that predicted for a monomer supporting their participation in protein complexes. The insoluble STEC fraction revealed enrichment of aggregation-prone proteins, including many that are part of large structure/function entities such as the ribosome, cytoskeleton and O-antigen biosynthesis cluster. Significance: Nearly all E. coli O157:H7 proteins encoded by prophage regions were expressed at low abundance levels or not detected. Comparative quantitative analyses of proteins from distinct cell lysate fractions allowed us to associate uncharacterized proteins with membrane attachment, potential participation in stable protein complexes, and susceptibility to aggregation as part of larger structural assemblies. [ABSTRACT FROM AUTHOR]- Published
- 2011
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5. Proteomic analysis of iron acquisition, metabolic and regulatory responses of Yersinia pestis to iron starvation.
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Pieper, Rembert, Shih-Ting Huang, Parmar, Prashanth P., Clark, David J., Alami, Hamid, Fleischmann, Robert D., Perry, Robert D., and Peterson, Scott N.
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YERSINIA pestis ,PLAGUE ,PROTEOMICS ,SIDEROPHORES ,PYRUVATES ,PROTEINS - Abstract
Background: The Gram-negative bacterium Yersinia pestis is the causative agent of the bubonic plague. Efficient iron acquisition systems are critical to the ability of Y. pestis to infect, spread and grow in mammalian hosts, because iron is sequestered and is considered part of the innate host immune defence against invading pathogens. We used a proteomic approach to determine expression changes of iron uptake systems and intracellular consequences of iron deficiency in the Y. pestis strain KIM6+ at two physiologically relevant temperatures (26°C and 37°C). Results: Differential protein display was performed for three Y. pestis subcellular fractions. Five characterized Y. pestis iron/siderophore acquisition systems (Ybt, Yfe, Yfu, Yiu and Hmu) and a putative iron/chelate outer membrane receptor (Y0850) were increased in abundance in iron-starved cells. The iron-sulfur (Fe-S) cluster assembly system Suf, adapted to oxidative stress and iron starvation in E. coli, was also more abundant, suggesting functional activity of Suf in Y. pestis under iron-limiting conditions. Metabolic and reactive oxygen-deactivating enzymes dependent on Fe-S clusters or other iron cofactors were decreased in abundance in iron-depleted cells. This data was consistent with lower activities of aconitase and catalase in iron-starved vs. iron-rich cells. In contrast, pyruvate oxidase B which metabolizes pyruvate via electron transfer to ubiquinone-8 for direct utilization in the respiratory chain was strongly increased in abundance and activity in iron-depleted cells. Conclusions: Many protein abundance differences were indicative of the important regulatory role of the ferric uptake regulator Fur. Iron deficiency seems to result in a coordinated shift from iron-utilizing to iron-independent biochemical pathways in the cytoplasm of Y. pestis. With growth temperature as an additional variable in proteomic comparisons of the Y. pestis fractions (26°C and 37°C), there was little evidence for temperature-specific adaptation processes to iron starvation. [ABSTRACT FROM AUTHOR]
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- 2010
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6. Transcriptional Regulation of Multi-Drug Tolerance and Antibiotic-Induced Responses by the Histone-Like Protein Lsr2 in M. tuberculosis.
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Colangeli, Roberto, Helb, Danica, Vilchèze, Catherine, Hazbón, Manzour Hernando, Lee, Chee-Gun, Safi, Hassan, Sayers, Brendan, Sardone, Irene, Jones, Marcus B., Fleischmann, Robert D., Peterson, Scott N., Jacobs Jr., William R., and Alland, David
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DRUG tolerance ,ANTIBIOTICS ,PROTEINS ,MYCOBACTERIUM tuberculosis ,ANTITUBERCULAR agents ,GENES ,GENE expression - Abstract
Multi-drug tolerance is a key phenotypic property that complicates the sterilization of mammals infected with Mycobacterium tuberculosis. Previous studies have established that iniBAC, an operon that confers multi-drug tolerance to M. bovis BCG through an associated pump-like activity, is induced by the antibiotics isoniazid (INH) and ethambutol (EMB). An improved understanding of the functional role of antibiotic-induced genes and the regulation of drug tolerance may be gained by studying the factors that regulate antibiotic-mediated gene expression. An M. smegmatis strain containing a lacZ gene fused to the promoter of M. tuberculosis iniBAC (P
iniBAC ) was subjected to transposon mutagenesis. Mutants with constitutive expression and increased EMB-mediated induction of PiniBAC ::lacZ mapped to the lsr2 gene (MSMEG6065), a small basic protein of unknown function that is highly conserved among mycobacteria. These mutants had a marked change in colony morphology and generated a new polar lipid. Complementation with multi-copy M. tuberculosis lsr2 (Rv3597c) returned PiniBAC expression to baseline, reversed the observed morphological and lipid changes, and repressed PiniBAC induction by EMB to below that of the control M. smegmatis strain. Microarray analysis of an lsr2 knockout confirmed upregulation of M. smegmatis iniA and demonstrated upregulation of genes involved in cell wall and metabolic functions. Fully 121 of 584 genes induced by EMB treatment in wild-type M. smegmatis were upregulated ("hyperinduced") to even higher levels by EMB in the M. smegmatis lsr2 knockout. The most highly upregulated genes and gene clusters had adenine-thymine (AT)-rich 5-prime untranslated regions. In M. tuberculosis, overexpression of lsr2 repressed INH-mediated induction of all three iniBAC genes, as well as another annotated pump, efpA. The low molecular weight and basic properties of Lsr2 (pI 10.69) suggested that it was a histone-like protein, although it did not exhibit sequence homology with other proteins in this class. Consistent with other histone-like proteins, Lsr2 bound DNA with a preference for circular DNA, forming large oligomers, inhibited DNase I activity, and introduced a modest degree of supercoiling into relaxed plasmids. Lsr2 also inhibited in vitro transcription and topoisomerase I activity. Lsr2 represents a novel class of histone-like proteins that inhibit a wide variety of DNA-interacting enzymes. Lsr2 appears to regulate several important pathways in mycobacteria by preferentially binding to AT-rich sequences, including genes induced by antibiotics and those associated with inducible multi-drug tolerance. An improved understanding of the role of lsr2 may provide important insights into the mechanisms of action of antibiotics and the way that mycobacteria adapt to stresses such as antibiotic treatment. [ABSTRACT FROM AUTHOR]- Published
- 2007
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7. Phase variable desialylation of host proteins that bind toStreptococcus pneumoniae in vivoand protect the airway.
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King, Samantha J., Hippe, Karen R., Gould, Jane M., Bae, Deborah, Peterson, Scott, Cline, Robin T., Fasching, Claudine, Janoff, Edward N., and Weiser, Jeffrey N.
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STREPTOCOCCUS pneumoniae ,PROTEINS ,GENOTYPE-environment interaction ,GENE expression ,STREPTOCOCCAL diseases ,BIOCHEMISTRY - Abstract
Most clinical isolates ofStreptococcus pneumoniaeconsist of heterogeneous populations of at least two colony phenotypes, opaque and transparent, selected for in the bloodstream and nasopharynx, respectively. Microarray analysis revealed 24orfsthat demonstrated differences in expression greater than twofold between variants of independent strains. Twenty-one of these showed increased expression in the transparent variants, including 11 predicted to be involved in sugar metabolism. A single genomic region contains seven of these loci including the gene that encodes the neuraminidase, NanA. In contrast to previous studies, there was no contribution of NanA to adherence ofS. pneumoniaeto epithelial cells or colonization in an animal model. However, we observed NanA-dependent desialylation of human airway components that bind to the organism and may mediate bacterial clearance. Targets of desialylation included human lactoferrin, secretory component, and IgA2 that were shown to be present on the surface of the pneumococcusin vivoduring pneumococcal pneumonia. The efficiency of desialylation was increased in the transparent variants and enhanced for host proteins binding to the surface ofS. pneumoniae. Because deglycosylation affects the function of many host proteins, NanA may contribute to a protease-independent mechanism to modify bound targets and facilitate enhanced survival of the bacterium. [ABSTRACT FROM AUTHOR]
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- 2004
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8. Analysis of Deinococcus radiodurans's Transcriptional Response to Ionizing Radiation and Desiccation Reveals Novel Proteins That Contribute to Extreme Radioresistance.
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Tanaka, Masashi, Earl, Ashlee M., Howell, Heather A., Mie-Jung Park, Eisen, Jonathan A., Peterson, Scott N., and Battista, John R.
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IONIZING radiation , *RADIATION , *GENES , *PROTEINS , *MICROBIAL genomics , *EPISTASIS (Genetics) , *GENETICS - Abstract
During the first hour after a sublethal dose of ionizing radiation, 72 genes were upregulated threefold or higher in D. radiodurans R1. Thirty-three of these loci were also among a set of 73 genes expressed ill R1 cultures recovering from desiccation. The five transcripts most highly induced in response to each stress are the same and encode proteins of unknown function. The genes (ddrA, ddrB, ddrC, ddrD, and pprA) corresponding to these transcripts were deleted, both alone and in all possible two-way combinations. Characterization of the mutant strains defines three epistasis groups that reflect different cellular responses to ionizing radiation-induced damage. The ddrA and ddrB gene products have complementary activities and inactivating both loci generates a strain that is more sensitive to ionizing radiation than strains in which either single gene has been deleted. These proteins appear to mediate efficient RecA-independent processes connected to ionizing radiation resistance. The pprA gene product is not necessary for homologous recombination during natural transformation, but nevertheless may participate in a RecA-dependent process during recovery from radiation damage. These characterizations clearly demonstrate that novel mechanisms significantly contribute to the ionizing radiation resistance in D. radiodurans. [ABSTRACT FROM AUTHOR]
- Published
- 2004
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