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Epigenetic Effects Of Benzo(A)Pyrene In Fundulus Heteroclitus And Danio Rerio, Xiefan Fang

Electronic Theses and Dissertations

DNA methylation is one of the epigenetic mechanisms that controls gene expression and is vulnerable to early life environmental toxicant exposures. Our goal was to use two fish models, Fundulus heteroclitus and Danio rerio (zebrafish), to study the benzo(a)pyrene (BaP) effects on DNA methylation status and whether the alterations could contribute to BaP-mediated reproductive and developmental toxicities. Initially, we used Fundulus to study BaP effects on glycine N-methyltransferase (GNMT) expression throughout development. Fundulus embryos were exposed to waterborne BaP at nominally 10 or 100 μg/L and both GNMT mRNA expression and enzyme activity were measured. Quantitative PCR and whole mount …

Stable Expression Of Tuberculosis Vaccine Antigen In Lettuce Chloroplasts, Priya Saikumar Lakshmi

Electronic Theses and Dissertations

Tuberculosis (TB) is caused by Mycobacterium tuberculosis and is one of the leading reasons of death by an infectious bacterial pathogen. The development of TB vaccines has been recognized as a major public health priority by the World Health Organization. In this study, a potential candidate antigen, ESAT-6 (6 kDa early secretory antigenic target) was fused with cholera toxin B subunit (CTB). Transplastomic lettuce plants were generated expressing these fusion proteins. Site-specific transgene integration into the chloroplast genome was confirmed by polymerase chain reaction and Southern blot analysis. In transplastomic leaves, expression levels of fusion protein (CTB-ESAT6) varied depending upon …

Evolutionary Relationships Among Staphylococci And The Prevention Of Staphylococcus Aureus Nasal Colonization, Ryan Paul Lamers

Electronic Theses and Dissertations

Staphylococcus is a significant cause of human infection and mortality, worldwide. Currently, there are greater than 60 taxa within Staphylococcus, and nearly all are pathogenic. The collective potential for virulence among species of Staphylococcus heightens the overall clinical significance of this genus and argues for a thorough understanding of the evolutionary relationships among species. Within Staphylococcus, aureus is the most common cause of human infection, where nasal carriage of this bacterium is a known risk factor for autoinfection. The predisposition to infection by nasal carriers of S. aureus, and the ease with which strains are transferred between individuals, suggests that …

Synthesis, Characterization And Antibacterial Activity Of Silver Embedded Silica Nanoparticle/Nanogel Formulation, Roseline Menezes

Electronic Theses and Dissertations

The antibacterial property of silver (Ag) has been known since ancient time. It is reported in the literature that silver nanoparticles (AgNPs) exhibit improved antibacterial properties in comparison to silver ions of equivalent metallic Ag concentration. Such improvement in antibacterial activities is due to the high surface area to volume ratio of AgNPs (which facilitates interaction with the bacterial cells), increased release of silver ions and direct intra-cellular uptake of AgNPs leading to localized release of Ag ions. To date, over 300 consumer products containing AgNPs are available in the market and the inventory is rapidly expanding. The antibacterial efficacy …

Expression And Functional Evaluation Of Exendin 4 Fused To Cholera Toxin B Subunit In Tobacco Chloroplast To Treat Type 2 Diabetes, Ramya Nityanandam

Electronic Theses and Dissertations

The prevalence of type 2 diabetes has been steadily increasing around the globe. Glucagon like peptide (GLP-1), a powerful incretin increases insulin secretion in a glucose dependent manner. But GLP-1 is subjected to rapid enzymatic degradation (half-life: 2 min in circulation). The commercially available GLP-1 analog, exenatide has a longer half life with potent insulinotropic effects (about 2.4 hr) which requires cold storage and daily subcutaneous injections. In this study, exendin 4 (EX4), lizard derived GLP-1R agonist, was expressed as cholera toxin B subunit (CTB)-fusion protein in chloroplasts of tobacco to facilitate transmucosal delivery in the gut by utilizing the …

Expression Of Trichoderma Reesei Beta]-Mannanase In Tobacco Chloroplasts And Its Utilization In Lignocellulosic Woody Biomass Hydrolysis, Pankaj M. Agrawal

Electronic Theses and Dissertations

Lignocellulosic ethanol offers a promising alternative to conventional fossil fuels. One among the major limitations in the lignocellulosic biomass hydrolysis is unavailability of efficient and environmentally biomass degrading technologies. Plantbased production of these enzymes on large scale offers a cost effective solution. Cellulases, hemicellulases including mannanases and other accessory enzymes are required for conversion of lignocellulosic biomass into fermentable sugars. β- mannanase catalyzes endo-hydrolysis of the mannan backbone, a major constituent of woody biomass. In this study, man1 gene encoding β-mannanase was isolated from Trichoderma reesei and expressed via the chloroplast genome. PCR and Southern hybridization analysis confirmed the site-specific …

Short Peptides As Inhibitors Of Amyloid Aggregation, Bradley Neddenriep, Anastasia Calciano, Daniel Conti, Erin Sauve, Marissa Paterson, Edward Bruno, David A. Moffet

Chemistry and Biochemistry Faculty Works

The misfolding and aggregation of proteins into amyloid has been linked to a variety of age-related diseases. Aggregation of proteins, such as Aβ in Alzheimer's disease and Islet Amyloid Polypeptide (IAPP, amylin) in type 2 diabetes, appears to lead to the formation of toxic assemblies. These assemblies range in size from small oligomers (2-8 proteins) to large fibrils (thousands of proteins). It remains unclear how these amyloidogenic proteins misfold and form toxic species, but growing evidence suggests that inhibiting the aggregation of these proteins could slow, if not prevent altogether, the progression of these diseases. We describe the use of …

Quantifying Agonist Activity At G Protein-Coupled Receptors, Frederick J. Ehlert, Hinako Suga, Michael T. Griffin

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

When an agonist activates a population of G protein-coupled receptors (GPCRs), it elicits a signaling pathway that culminates in the response of the cell or tissue. This process can be analyzed at the level of a single receptor, a population of receptors, or a downstream response. Here we describe how to analyze the downstream response to obtain an estimate of the agonist affinity constant for the active state of single receptors.

Receptors behave as quantal switches that alternate between active and inactive states (Figure 1). The active state interacts with specific G proteins or other signaling partners. In the absence …

Bio-Functionalized Clay Nanoparticles For Wound Healing Applications, Christopher Anthony Vaiana

Browse all Theses and Dissertations

Wound healing is a complex, multi-step process that can be summarized into three stages, namely hemostasis and inflammation, proliferation, and finally tissue remodeling. Battlefield wound healing demands rapid hemostasis using clotting or cauterizing agents to immediately limit blood loss, but this occurs at the expense of proper tissue repair beyond hemostasis. Layered silicate clays such as kaolin and montmorillonite (MMT) have been previously shown to induce blood clotting due to their ability to form charged interactions with clotting factors. The charge characteristics of sodium MMT (Na-MMT) also enable functionalization with active biomolecules. Herein we first functionalize three types of alumoinosilicate …

Interrogation Of The Distal Gut Microbiota Of Healthy Adolescents And Those With Irritable Bowel Syndrome, Laura J. Rigsbee

Browse all Theses and Dissertations

The human-associated microbiota has been the focus of much current research, with the microbiota inhabiting the gastrointestinal tract of particular interest. These organisms play many roles in human health and well-being. However, shifts in the composition of the intestinal microbiota have been associated with diseases such as irritable bowel syndrome, inflammatory bowel disease, and colon cancer. Several recent studies have reported on the distal gut microbiota composition of healthy adults and those with IBS, while there is a lack of studies devoted to adolescents. This study utilized a custom-designed Affymetrix Microbiota Array capable of detecting 775 phylo-species of intestinal bacteria …

Functional Metabolomics' Enhances Assessment Of Tissue Dysfunction As Demonstrated In A Rat Model Of Sub-Acute D-Serine Exposure, Isaie Sibomana

Browse all Theses and Dissertations

We describe a methodology that combines urinary metabolomics with a tissue-specific stressor administration to enhance assessment of tissue function. Kidney function in rats was mildly compromised with a sub-acute dose of D-serine and stressed with furosemide. NMR-based metabolomics analyses showed no detectable effects due to D-serine alone; but furosemide or D-serine + furosemide groups, classified separately from each other, and from control. Furosemide alone caused a ca. 2-fold increase in glucose, lactate, choline, and a 30% decrease in TCA intermediates (p≤0.05). D-serine suppressed these effects and produced a 1.7-fold increase in a p-phenolic acid-derivative of tyrosine (PAdY) relative to control …

Novel Role Of Mecp2 In Developing Oligodendrocytes And Myelination, Daniel Moore

Theses and Dissertations

Methyl-CpG-binding protein 2 (MeCP2 is) is an epigenetic regulator that binds to methylated DNA. Initially identified as transcriptional repressor, MeCP2 also binds to different proteins functioning as gene activator. Importantly, MecCP2 gene mutations and changes in MeCP2 levels are associated to several forms of mental retardation and autism-related disorders; including Rett, a neurodevelopmental disorder affecting primarily girls. While brain MeCP2 was considered to be exclusively neuronal, this regulator is also present in glia. We found that oligodendrocytes, the myelinating cells of the central nervous system (CNS), express particularly high MeCP2 levels at a developmental stage that precedes their final maturation. …

Structural And Functional Alteration Of Full Length Pparα And Lxrα By Fatty Acids And Their Thioesters, Madhumitha Balanarasimha

Browse all Theses and Dissertations

Peroxisome proliferator-activated receptors (PPAR) and liver X receptors (LXR) are known to play important roles in fatty acid metabolism, interact with each other, and function as heterodimeric partners. Although previous studies indicate that PPARα is activated by long chain fatty acyl-CoA thioesters (LCFA-CoA) and polyunsaturated fatty acids, little is known about the effects of these ligands on the function or interaction of PPARα and LXRα. In this study, hPPARα and hLXRα were shown to directly interact by circular dichroism, fluorescent binding assays, and co-immunoprecipitation. Further experiments suggested that although fatty acids resulted in small structural changes, they significantly altered binding …

Carbenoxolone Blocks The Light-Evoked Rise In Intracellular Calcium In Isolated Melanopsin Ganglion Cell Photoreceptors, Jayne R. Bramley, Erin M. Wiles, Patricia J. Sollars, Gary E. Pickard

School of Veterinary and Biomedical Sciences: Faculty Publications

Background: Retinal ganglion cells expressing the photopigment melanopsin are intrinsically photosensitive (ipRGCs). These ganglion cell photoreceptors send axons to several central targets involved in a variety of functions. Within the retina ipRGCs provide excitatory drive to dopaminergic amacrine cells via glutamatergic signals and ipRGCs are coupled to widefield GABAergic amacrine cells via gap junctions. However, the extent to which ipRGCs are coupled to other retinal neurons in the ganglion cell layer via gap junctions is unclear. Carbenoxolone, a widely employed gap junction inhibitor, greatly reduces the number of retinal neurons exhibiting non-rod, non-cone mediated light-evoked Ca²⁺ signals suggesting extensive …

Y-Like Retinal Ganglion Cells Innervate The Dorsal Raphe Nucleus In The Mongolian Gerbil (Meriones Unguiculatus), Liju Luan, Chaoran Ren, Benson Wui-Man Lau, Jian Yang, Gary E. Pickard, Kwok-Fai So, Mingliang Pu

School of Veterinary and Biomedical Sciences: Faculty Publications

Background: The dorsal raphe nucleus (DRN) of the mesencephalon is a complex multi-functional and multi-transmitter nucleus involved in a wide range of behavioral and physiological processes. The DRN receives a direct input from the retina. However little is known regarding the type of retinal ganglion cell (RGC) that innervates the DRN. We examined morphological characteristics and physiological properties of these DRN projecting ganglion cells.

Methodology/Principal Findings: The Mongolian gerbils are highly visual rodents with a diurnal/crepuscular activity rhythm. It has been widely used as experimental animals of various studies including seasonal affective disorders and depression. Young adult gerbils were used …

Challenges And Opportunities For Toxicology In Mexico, Rodrigo Franco, Balam Muñoz

School of Veterinary and Biomedical Sciences: Faculty Publications

We have developed this Special Issue titled “Challenges and Opportunities for Toxicology in Mexico” with the aim to highlight not only the challenges toxicology research faces in Mexico, but also the efforts and drive towards cutting edge research to address them. Altogether, this special issue should be a valuable source of information for all readers with an interest in toxicology and human health.

Mexico is an important economy worldwide and is a major exporter of several supplies and commodities. Because of this, its industry is a source of occupational exposure to several chemical derivatives (Nieusma 2011). The situation of occupational …

Intrinsically Photosensitive Retinal Ganglion Cells, Gary E. Pickard, Patricia J. Sollars

School of Veterinary and Biomedical Sciences: Faculty Publications

Intrinsically photosensitive retinal ganglion cells (ipRGCs) respond to light in the absence of all rod and cone photoreceptor input. The existence of these ganglion cell photoreceptors, although predicted from observations scattered over many decades, was not established until it was shown that a novel photopigment, melanopsin, was expressed in retinal ganglion cells of rodents and primates. Phototransduction in mammalian ipRGCs more closely resembles that of invertebrate than vertebrate photoreceptors and appears to be mediated by transient receptor potential channels. In the retina, ipRGCs provide excitatory drive to dopaminergic amacrine cells and ipRGCs are coupled to GABAergic amacrine cells via gap …

Long-Term Clinicopathological Characteristics Of Alpacas Naturally Infected With Bovine Viral Diarrhea Virus Type Ib, D. Bedenice, Edward J. Dubovi, Clayton Kelling, Jamie N Henningson, Christina L. Topliff, N. Parry

School of Veterinary and Biomedical Sciences: Faculty Publications

Background: Substantial bovine viral diarrhea virus (BVDV)-related production losses in North American alpaca herds have been associated with BVDV type Ib infection.

Objectives: To classify and differentiate the long-term clinicopathological characteristics of BVDV type Ib infection of al- paca crias, after natural virus exposure. We hypothesized that persistently infected (PI) alpacas specifically demonstrate growth retardation, clinicopathological evidence of opportunistic infections, and early mortality.

Animals: Thirty-five crias naturally exposed to BVDV (18 acute, 3 chronic, 14 PIs), and 19 healthy cohort controls of 5 northeastern alpaca farms were prospectively evaluated over 2 years (September 2005–September 2008).

Methods: Observational cohort-control study.

Results: …

Gender Differences In Cns Autoimmunity Induced By Mimicry Epitope For Plp 139–151 In Sjl Mice, Chandirasegara Massilamany, Sivasubramani Thulasingam, David Steffen, Jay Reddy

Jay Reddy Publications

Development of multiple sclerosis (MS) is more prevalent in females than in males, but the underlying mechanisms are not clear. Microbial infections have been suspected as triggers of MS and it is not known whether gender differences in reactivity to environmental antigens contribute to the disease pathogenesis. We demonstrated that ACA 83–95, a mimicry epitope from Acanthamoeba castellanii for proteolipid protein (PLP) 139–151, induces clinical signs of encephalomyelitis in both male and female SJL mice. Conversely ACA 83–95-induced effector cells from males fail to induce disease in female mice. Although we found no gender differences in the frequencies of antigen-specific …

Rnai Screening Reveals Requirement For Host Cell Secretory Pathway In Infection By Diverse Families Of Negative-Strand Rna Viruses, Debasis Panda, Anshuman Das, Phat X. Dinh, Sakthivel Subramaniam, Debasis Nayak, Nicholas J. Barrows, James L. Pearson, Jesse Thompson, David L. Kelly, Istvan Ladunga, Asit K. Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

Negative-strand (NS) RNA viruses comprise many pathogens that cause serious diseases in humans and animals. Despite their clinical importance, little is known about the host factors required for their infection. Using vesicular stomatitis virus (VSV), a prototypic NS RNA virus in the family Rhabdoviridae, we conducted a human genomewide siRNA screen and identified 72 host genes required for viral infection. Many of these identified genes were also required for infection by two other NS RNA viruses, the lymphocytic choriomeningitis virus of the Arenaviridae family and human parainfluenza virus type 3 of the Paramyxoviridae family. Genes affecting different stages of …

Consensus-Based Reporting Standards For Diagnostic Test Accuracy Studies For Paratuberculosis In Ruminants, Ian A. Gardner, Søren S. Nielsen, Richard J. Wittington, Michael T. Collins, Douwe Bakker, Beth Harris, Srinand Sreevatsan, Jason E. Lombard, Raymond Sweeney, David R. Smith, Jerrie Gavalchin, Shigetoshi Eda

School of Veterinary and Biomedical Sciences: Faculty Publications

The Standards for Reporting of Diagnostic Accuracy (STARD) statement was developed to encourage complete and transparent reporting of key elements of test accuracy studies in human medicine. The statement was motivated by widespread evidence of bias in test accuracy studies and the finding that incomplete or absent reporting of items in the STARD checklist was associated with overly optimistic estimates of test performance characteristics. Although STARD principles apply broadly, specific guidelines do not exist to account for unique considerations in livestock studies such as herd tests, potential use of experimental challenge studies, a more diverse group of testing purposes and …

Genome-Wide Ribosome Profiling Reveals Complex Translational Regulation In Response To Oxidative Stress, Maxim V. Gerashchenko, Alexei V. Lobanov, Vadim N. Gladyshev

Department of Biochemistry: Faculty Publications

Information on unique and coordinated regulation of transcription and translation in response to stress is central to the understanding of cellular homeostasis. Here we used ribosome profiling coupled with next-generation sequencing to examine the interplay between transcription and translation under conditions of hydrogen peroxide treatment in Saccharomyces cerevisiae. Hydrogen peroxide treatment led to a massive and rapid increase in ribosome occupancy of short upstream ORFs, including those with non-AUG translational starts, and of the N-terminal regions of ORFs that preceded the transcriptional response. In addition, this treatment induced the synthesis of N-terminally extended proteins and elevated stop codon read-through …

Reduced Utilization Of Selenium By Naked Mole Rats Due To A Specific Defect In Gpx1 Expression, Marina V. Kasaikina, Alexei V. Lobanov, Mikalai I. Malinouski, Byung Cheon Lee, Javier Seravalli, Dmitri E. Fomenko, Anton A. Turanov, Lydia Finney, Stefan Vogt, Thomas J. Park, Richard A. Miller, Dolph L. Hatfield, Vadim N. Gladyshev

Department of Biochemistry: Faculty Publications

Naked mole rat (MR) Heterocephalus glaber is a rodent model of delayed aging because of its unusually long life span (>28 years). It is also not known to develop cancer. In the current work, tissue imaging by x-ray fluorescence microscopy and direct analyses of trace elements revealed low levels of selenium in the MR liver and kidney, whereas MR and mouse brains had similar selenium levels. This effect was not explained by uniform selenium deficiency because methionine sulfoxide reductase activities were similar in mice and MR. However, glutathione peroxidase activity was an order of magnitude lower inMRliver and kidney …

A 4-Selenocysteine, 2-Selenocysteine Insertion Sequence (Secis) Element Methionine Sulfoxide Reductase From Metridium Senile Reveals A Non-Catalytic Function Of Selenocysteines, Byung Cheon Lee, Alexey V. Lobanov, Stefano M. Marino, Alaattin Kaya, Javier Seravalli, Dolph L. Hatfield, Vadim N. Gladyshev

Department of Biochemistry: Faculty Publications

Selenocysteine (Sec) residues occur in thiol oxidoreductase families, and functionally characterized selenoenzymes typically have a single Sec residue used directly for redox catalysis. However, how new Sec residues evolve and whether non-catalytic Sec residues exist in proteins is not known. Here, we computationally identified several genes with multiple Sec insertion sequence (SECIS) elements, one of which was a methionine-Rsulfoxide reductase (MsrB) homolog from Metridium senile that has four in-frame UGA codons and two nearly identical SECIS elements. One of the UGA codons corresponded to the conserved catalytic Sec or Cys in MsrBs, whereas the three other UGA codons evolved recently …

Escherichia Coli Thioredoxin-Like Protein Ybbn Contains An Atypical Tetratricopeptide Repeat Motif And Is A Negative Regulator Of Groel, Jiusheng Lin, Mark A. Wilson

Department of Biochemistry: Faculty Publications

Many proteins contain a thioredoxin (Trx)-like domain fused with one or more partner domains that diversify protein function by the modular construction of new molecules. The Escherichia coli protein YbbN is a Trx-like protein that contains a C-terminal domain with low homology to tetratricopeptide repeat motifs. YbbN has been proposed to act as a chaperone or co-chaperone that aids in heat stress response andDNAsynthesis. We report the crystal structure of YbbN, which is an elongated molecule with a mobile Trx domain and four atypical tetratricopeptide repeat motifs. The Trx domain lacks a canonical CXXC active site architecture and is not …

Defining A Relationship Between Dietary Fatty Acids And The Cytochrome P450 System In A Mouse Model Of Fatty Liver Disease, Monika Gonzalez, Whitney Sealls, Elliot D. Jesch, M. Julia Brosnan, Istvan Ladunga, Xinxin Ding, Paul N. Black, Concetta C. Dirusso

Department of Biochemistry: Faculty Publications

Liver-specific ablation of cytochrome P450 reductase in mice (LCN) results in hepatic steatosis that can progress to steatohepatitis characterized by inflammation and fibrosis. The specific cause of the fatty liver phenotype is poorly understood but is hypothesized to result from elevated expression of genes encoding fatty acid synthetic genes. Since expression of these genes is known to be suppressed by polyunsaturated fatty acids, we performed physiological and genomics studies to evaluate the effects of dietary linoleic and linolenic fatty acids (PUFA) or arachidonic and decosahexaenoic acids (HUFA) on the hepatic phenotypes of control and LCN mice by comparison with a …

Functional Diversification Of Thylakoidal Processing Peptidases In Arabidopsis Thaliana, Shih-Chi Hsu, Joshua K. Endow, Nicholas J. Ruppel, Rebecca Roston, Amy J. Baldwin, Kentaro Inoue

Department of Biochemistry: Faculty Publications

Thylakoidal processing peptidase (TPP) is responsible for removing amino-terminal thylakoid-transfer signals from several proteins in the thylakoid lumen. Three TPP isoforms are encoded by the nuclear genome of Arabidopsis thaliana. Previous studies showed that one of them termed plastidic type I signal peptidase 1 (Plsp1) was necessary for processing three thylakoidal proteins and one protein in the chloroplast envelope in vivo. The lack of Plsp1 resulted in seedling lethality, apparently due to disruption of proper thylakoid development. The physiological roles of the other two TPP homologs remain unknown. Here we show that the three A. thaliana TPP isoforms …

Enzymatic Defects Underlying Hereditary Glutamate Cysteine Ligase Deficiency Are Mitigated By Association Of The Catalytic And Regulatory Subunits, Melanie Neely Willis, Yilin Liu, Ekaterina I. Biterova, Melanie A. Simpson, Heejeong Kim, Jaekwon Lee, Joseph J. Barycki

Department of Biochemistry: Faculty Publications

Glutamate cysteine ligase (GCL) deficiency is a rare autosomal recessive trait that compromises

production of glutathione, a critical redox buffer and enzymatic cofactor. Patients have markedly

reduced levels of erythrocyte glutathione, leading to hemolytic anemia and in some cases,

impaired neurological function. Human glutamate cysteine ligase is a heterodimer comprised of a

catalytic (GCLC) and a regulatory subunit (GCLM), which catalyzes the initial rate limiting step

in glutathione production. Four clinical missense mutations have been identified within GCLC:

Arg127Cys, Pro158Leu, His370Leu, and Pro414Leu. Here, we have evaluated the impacts of

these mutations on enzymatic function in vivo and in vitro …

The Lyr Protein Mzm1 Functions In The Insertion Of The Rieske Fe/S Protein In Yeast Mitochondria, Aaron Atkinson, Pamela Smith, Jennifer L. Fox, Tie-Shong Cui, Oleh Khalimonchuk, Dennis R. Winge

Department of Biochemistry: Faculty Publications

The assembly of the cytochrome bc1 complex in Saccharomyces cerevisiae is shown to be conditionally dependent on a novel factor, Mzm1. Cells lacking Mzm1 exhibit a modest bc₁ defect at 30°C, but the defect is exacerbated at elevated temperatures. Formation of bc₁ is stalled in mzm1 Δ cells at a late assembly intermediate lacking the Rieske iron-sulfur protein Rip1. Rip1 levels are markedly attenuated in mzm1 Δ cells at elevated temperatures. Respiratory growth can be restored in the mutant cells by the overexpression of the Rip1 subunit. Elevated levels of Mzm1 enhance the stabilization of Rip1 through …

Rpir Homologues May Link Staphylococcus Aureus Rnaiii Synthesis And Pentose Phosphate Pathway Regulation, Yefei Zhu, Nandakumar Madayiputhiya, Marat R. Sadykov, Nandakumar Madayiputhiya, Thanh T. Luong, Rosmarie Gaupp, Chia Y. Lee, Greg Somerville

Department of Biochemistry: Faculty Publications

Staphylococcus aureus is a medically important pathogen that synthesizes a wide range of virulence determinants. The synthesis of many staphylococcal virulence determinants is regulated in part by stress-induced changes in the activity of the tricarboxylic acid (TCA) cycle. One metabolic change associated with TCA cycle stress is an increased concentration of ribose, leading us to hypothesize that a pentose phosphate pathway (PPP)-responsive regulator mediates some of the TCA cycle-dependent regulatory effects. Using bioinformatics, we identified three potential ribose-responsive regulators that belong to the RpiR family of transcriptional regulators. To determine whether these RpiR homologues affect PPP activity and virulence determinant …