scholarly journals Guanine Limitation Results in CodY-Dependent and -Independent Alteration ofStaphylococcus aureusPhysiology and Gene Expression

2018 ◽  
Vol 200 (14) ◽  
Author(s):  
Alyssa N. King ◽  
Samiksha A. Borkar ◽  
David J. Samuels ◽  
Zachary Batz ◽  
Logan L. Bulock ◽  
...  
Keyword(s):  
Gene Expression ◽  
Staphylococcus Aureus ◽  
De Novo ◽  
Expression Profiles ◽  
Sugar Transport ◽  
Health Care Facilities ◽  
Gene Products ◽  
Nucleotide Synthesis ◽  
Content Type ◽  
The Impact

ABSTRACTInStaphylococcus aureus, the global transcriptional regulator CodY modulates the expression of hundreds of genes in response to the availability of GTP and the branched-chain amino acids isoleucine, leucine, and valine (ILV). CodY DNA-binding activity is high when GTP and ILV are abundant. When GTP and ILV are limited, CodY's affinity for DNA drops, altering expression of CodY-regulated targets. In this work, we investigated the impact of guanine nucleotides (GNs) onS. aureusphysiology and CodY activity by constructing aguaAnull mutant (ΔguaAstrain).De novobiosynthesis of guanine monophosphate is abolished due to theguaAmutation; thus, the mutant cells require exogenous guanosine for growth. We also found that CodY activity was reduced when we knocked outguaA, activating the Agr two-component system and increasing secreted protease activity. Notably, in a rich, complex medium, we detected an increase in alternative sigma factor B activity in the ΔguaAmutant, which results in a 5-fold increase in production of the antioxidant pigment staphyloxanthin. Under biologically relevant flow conditions, ΔguaAcells failed to form robust biofilms when limited for guanine or guanosine. Transcriptome sequencing (RNA-Seq) analysis of theS. aureustranscriptome during growth in guanosine-limited chemostats revealed substantial CodY-dependent and -independent alterations of gene expression profiles. Importantly, these changes increase production of proteases and δ-toxin, suggesting thatS. aureusexhibits a more invasive lifestyle when limited for guanosine. Further, gene products upregulated under GN limitation, including those necessary for lipoic acid biosynthesis and sugar transport, may prove to be useful drug targets for treating Gram-positive infections.IMPORTANCEStaphylococcus aureusinfections impose a serious economic burden on health care facilities and patients because of the emergence of strains resistant to last-line antibiotics. Understanding the physiological processes governing fitness and virulence ofS. aureusin response to environmental cues is critical for developing efficient diagnostics and treatments.De novopurine biosynthesis is essential for both fitness and virulence inS. aureussince inhibiting production cripplesS. aureus's ability to cause infection. Here, we corroborate these findings and show that blocking guanine nucleotide synthesis severely affectsS. aureusfitness by altering metabolic and virulence gene expression. Characterizing pathways and gene products upregulated in response to guanine limitation can aid in the development of novel adjuvant strategies to combatS. aureusinfections.

scholarly journals Formation of Staphylococcus aureus Biofilm in the Presence of Sublethal Concentrations of Disinfectants Studied via a Transcriptomic Analysis Using Transcriptome Sequencing (RNA-seq)

2017 ◽  
Vol 83 (24) ◽  
Author(s):  
M. Slany ◽  
J. Oppelt ◽  
L. Cincarova
Keyword(s):  
Gene Expression ◽  
Staphylococcus Aureus ◽  
Biofilm Formation ◽  
Transcriptome Sequencing ◽  
Expression Profiles ◽  
Bacterial Species ◽  
Rna Seq ◽  
Altered Expression ◽  
Content Type ◽  
Sublethal Concentrations

ABSTRACT Staphylococcus aureus is a common biofilm-forming pathogen. Low doses of disinfectants have previously been reported to promote biofilm formation and to increase virulence. The aim of this study was to use transcriptome sequencing (RNA-seq) analysis to investigate global transcriptional changes in S. aureus in response to sublethal concentrations of the commonly used food industry disinfectants ethanol (EtOH) and chloramine T (ChT) and their combination (EtOH_ChT) in order to better understand the effects of these agents on biofilm formation. Treatment with EtOH and EtOH_ChT resulted in more significantly altered expression profiles than treatment with ChT. Our results revealed that EtOH and EtOH_ChT treatments enhanced the expression of genes responsible for regulation of gene expression (sigB), cell surface factors (clfAB), adhesins (sdrDE), and capsular polysaccharides (cap8EFGL), resulting in more intact biofilm. In addition, in this study we were able to identify the pathways involved in the adaptation of S. aureus to the stress of ChT treatment. Further, EtOH suppressed the effect of ChT on gene expression when these agents were used together at sublethal concentrations. These data show that in the presence of sublethal concentrations of tested disinfectants, S. aureus cells trigger protective mechanisms and try to cope with them. IMPORTANCE So far, the effect of disinfectants is not satisfactorily explained. The presented data will allow a better understanding of the mode of disinfectant action with regard to biofilm formation and the ability of bacteria to survive the treatment. Such an understanding could contribute to the effort to eliminate possible sources of bacteria, making disinfectant application as efficient as possible. Biofilm formation plays significant role in the spread and pathogenesis of bacterial species.

scholarly journals Inactivation of thyA in Staphylococcus aureus Attenuates Virulence and Has a Strong Impact on Metabolism and Virulence Gene Expression

mBio ◽  
2014 ◽  
Vol 5 (4) ◽  
Author(s):  
Andre Kriegeskorte ◽  
Desiree Block ◽  
Mike Drescher ◽  
Nadine Windmüller ◽  
Alexander Mellmann ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Thymidylate Synthase ◽  
Molecular Basis ◽  
De Novo ◽  
Strong Impact ◽  
Small Colony Variants ◽  
Content Type ◽  
Long Term Treatment ◽  
Small Colony ◽  
The Impact

ABSTRACTStaphylococcus aureusthymidine-dependent small-colony variants (TD-SCVs) are frequently isolated from patients with chronicS. aureusinfections after long-term treatment with trimethoprim-sulfamethoxazole (TMP-SMX). While it has been shown that TD-SCVs were associated with mutations in thymidylate synthase (TS;thyA), the impact of such mutations on protein function is lacking. In this study, we showed that mutations inthyAwere leading to inactivity of TS proteins, and TS inactivity led to tremendous impact onS. aureusphysiology and virulence. Whole DNA microarray analysis of the constructed ΔthyAmutant identified severe alterations compared to the wild type. Important virulence regulators (agr,arlRS,sarA) and major virulence determinants (hla,hlb,sspAB, andgeh) were downregulated, while genes important for colonization (fnbA,fnbB,spa,clfB,sdrC, andsdrD) were upregulated. The expression of genes involved in pyrimidine and purine metabolism and nucleotide interconversion changed significantly. NupC was identified as a major nucleoside transporter, which supported growth of the mutant during TMP-SMX exposure by uptake of extracellular thymidine. The ΔthyAmutant was strongly attenuated in virulence models, including aCaenorhabditis eleganskilling model and an acute pneumonia mouse model. This study identified inactivation of TS as the molecular basis of clinical TD-SCV and showed thatthyAactivity has a major role forS. aureusvirulence and physiology.IMPORTANCEThymidine-dependent small-colony variants (TD-SCVs) ofStaphylococcus aureuscarry mutations in the thymidylate synthase (TS) gene (thyA) responsible forde novosynthesis of thymidylate, which is essential for DNA synthesis. TD-SCVs have been isolated from patients treated for long periods with trimethoprim-sulfamethoxazole (TMP-SMX) and are associated with chronic and recurrent infections. In the era of community-associated methicillin-resistantS. aureus, the therapeutic use of TMP-SMX is increasing. Today, the emergence of TD-SCVs is still underestimated due to misidentification in the diagnostic laboratory. This study showed for the first time that mutational inactivation of TS is the molecular basis for the TD-SCV phenotype and that TS inactivation has a strong impact onS. aureusvirulence and physiology. Our study helps to understand the clinical nature of TD-SCVs, which emerge frequently once patients are treated with TMP-SMX.

scholarly journals Staphylococcus aureus Responds to Physiologically Relevant Temperature Changes by Altering Its Global Transcript and Protein Profile

mSphere ◽  
2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Raeven A. Bastock ◽  
Emily C. Marino ◽  
Richard E. Wiemels ◽  
Donald L. Holzschu ◽  
Rebecca A. Keogh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Staphylococcus Aureus ◽  
Environmental Conditions ◽  
Large Temperature ◽  
Small Scale ◽  
Content Type ◽  
Temperature Changes ◽  
Invasive Infections ◽  
The Impact ◽  
Definite Temperature

ABSTRACT Staphylococcus aureus is an opportunistic pathogen that colonizes the anterior nares of 30 to 50% of the population. Colonization is most often asymptomatic; however, self-inoculation can give rise to potentially fatal infections of the deeper tissues and blood. Like all bacteria, S. aureus can sense and respond to environmental cues and modify gene expression to adapt to specific environmental conditions. The transition of S. aureus from the nares to the deeper tissues and blood is accompanied by changes in environmental conditions, such as nutrient availability, pH, and temperature. In this study, we perform transcriptomics and proteomics on S. aureus cultures growing at three physiologically relevant temperatures, 34°C (nares), 37°C (body), and 40°C (pyrexia), to determine if small scale, biologically meaningful alterations in temperature impact S. aureus gene expression. Results show that small but definite temperature changes elicit a large-scale restructuring of the S. aureus transcriptome and proteome in a manner that, most often, inversely correlates with increasing temperature. We also provide evidence that a large majority of these changes are modulated at the posttranscriptional level, possibly by sRNA regulatory elements. Phenotypic analyses were also performed to demonstrate that these changes have physiological relevance. Finally, we investigate the impact of temperature-dependent alterations in gene expression on S. aureus pathogenesis and demonstrate decreased intracellular invasion of S. aureus grown at 34°C. Collectively, our results demonstrate that small but biologically meaningful alterations in temperature influence S. aureus gene expression, a process that is likely a major contributor to the transition from a commensal to pathogen. IMPORTANCE Enteric bacterial pathogens, like Escherichia coli, are known to experience large temperature differences as they are transmitted through the fecal oral route. This change in temperature has been demonstrated to influence bacterial gene expression and facilitate infection. Staphylococcus aureus is a human-associated pathogen that can live as a commensal on the skin and nares or cause invasive infections of the deeper tissues and blood. Factors influencing S. aureus nasal colonization are not fully understood; however, individuals colonized with S. aureus are at increased risk of invasive infections through self-inoculation. The transition of S. aureus from the nose (colonization) to the body (infection) is accompanied by a modest but definite temperature increase, from 34°C to 37°C. In this study, we investigate whether these host-associated small temperature changes can influence S. aureus gene expression. Results show widespread changes in the bacterial transcriptome and proteome at three physiologically relevant temperatures (34°C, 37°C, and 40°C).

The Presence of Multilineage Dysplasia (MLD) Has No Significant Impact On Biological, Clinico-Pathological, and Prognostic Features in AML with Mutated Nucleophosmin (NPM1).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2618-2618
Author(s):  
Torsten Haferlach ◽  
Katja Macijewski ◽  
Tamara Weiss ◽  
Ulrike Bacher ◽  
Susanne Schnittger ◽  
...  
Keyword(s):  
Gene Expression ◽  
De Novo ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Control Group ◽  
Microarray Gene Expression ◽  
Prognostic Features ◽  
Multilineage Dysplasia ◽  
Equity Ownership ◽  
The Impact

Abstract Abstract 2618 Poster Board II-594 AML with mutated nucleophosmin (NPM1) is a provisional entity in the WHO-2008 classification of myeloid neoplasms. A yet unresolved issue concerning NPM1-mutated AML is the biological and clinical significance of concomitant multilineage dysplasia (MLD). So far, NPM1+ AML with MLD is classified as AML with myelodysplasia-related changes in the new WHO classification. Therefore, we addressed the impact of MLD in 378 de novo AML patients with mutated/cytoplasmic NPM1 and performed comparison of cytomorphological features, cytogenetics, the FLT3 mutation status, and gene expression profiles in patients with and without MLD. MLD - as defined by dysplastic features in at least two hematopoietic lineages by cytomorphology - was present in 95/378 (25.1%) cases. Mean age (±standard deviation) was 52.1±14.0 years in the group with MLD and 54.8±14.5 in the group without MLD (p=0.11). Males comprised 50/95 (52.6%) in the group with MLD vs. 119/283 (42%) in the group without MLD (p=0.075). Morphological subtypes according to FAB/WHO were available in 365 cases (96.5%) and did not differ significantly between both groups. The median WBC was 17.1 G/l (range: 0.9–211.0 G/l) in the group with MLD and 35.6 G/l (range: 0.5–600.0 G/l) in the group without MLD (p=0.0027). Absence of CD34 expression was observed in 60/74 (81.1%) and 172/212 (81.1%) cases of the groups with and without MLD, respectively (p=1.0). Cytogenetic data was available in all 378 cases: An abnormal karyotype was present in 15/95 (15.8%) cases with MLD and in 37/283 (13.1%) cases without MLD (p=0.49). Molecular analyses detected the FLT3-ITD in 16/91 (17.6%) cases tested with MLD and in 110/276 (39.9%) cases without MLD (p<0.001). FLT3-TKD mutations were found in 7/80 (8.8%) patients within the group with MLD and in 21/221 (9.5%) patients within the group without MLD, respectively (p=1.0). Moreover, NPM1-mutated AML with or without MLD demonstrated non-discriminative microarray gene expression profiles (Affymetrix HG-U133 Plus 2.0). The gene expression profiles, however, clearly differed between NPM1-mutated AML and NPM1-wildtype cases as control group, e.g. by detectable downregulation of CD34 and upregulation of the characteristic HOX gene signature. This indicates that NPM1 mutations rather than MLD dictate the distinctive features of this AML subtype. With respect to clinical relevance, presence of MLD had no significant influence on overall survival (OS), however, it was related to a better event-free survival (EFS, median 33.3 vs. 13.9 months, p=0.0412), which is likely due to the fact that FLT3-ITD were less common in the MLD+ group (p=0.001). In addition also in our cohort the presence of an FLT3-ITD was associated with a significantly shorter EFS (median 11.2 vs. 22.3 months, p=0.0002) and a significantly shorter OS (median 12.5 months vs. not reached, p<0.0001). MLD also had no impact on outcome if analyzed within the groups with or without FLT3-ITD, respectively. Multivariate analysis revealed FLT3-ITD as the only parameter independently related to EFS (p=0.0051) and OS (p=0.0024). In conclusion, the discrimination of AML with MLD from AML without MLD in NPM1-mutated AML does not lead to distinct entities of AML since biologic features and outcome are largely similar. The FLT3-ITD mutation, however, again was confirmed to be an important biological parameter in AML with NPM1 mutations as demonstrated by a significantly worse outcome. Thus, our data underlines that NPM1+ AML is a distinct entity and further suggests that NPM1+ AML should be considered as one group irrespective of the presence or absence of MLD. Disclosures: Haferlach: MLL Munich Leukemia Laboratory: Equity Ownership. Macijewski:MLL Munich Leukemia Laboratory: Employment. Weiss:MLL Munich Leukemia Laboratory: Employment. Schnittger:MLL Munich Leukemia Laboratory: Equity Ownership. Kern:MLL Munich Leukemia Laboratory: Equity Ownership. Kohlmann:MLL Munich Leukemia Laboratory: Employment. Miesner:MLL Munich Leukemia Laboratory: Employment. Haferlach:MLL Munich Leukemia Laboratory: Equity Ownership. Falini:Xenomics: Patents & Royalties.

scholarly journals The Pseudomonas aeruginosa Transcriptional Landscape Is Shaped by Environmental Heterogeneity and Genetic Variation

mBio ◽  
2015 ◽  
Vol 6 (4) ◽  
Author(s):  
Andreas Dötsch ◽  
Monika Schniederjans ◽  
Ariane Khaledi ◽  
Klaus Hornischer ◽  
Sebastian Schulz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pseudomonas Aeruginosa ◽  
Genetic Variation ◽  
Expression Profiles ◽  
Phenotypic Variability ◽  
Gene Expression Profiles ◽  
Environmental Cues ◽  
Content Type ◽  
The Impact ◽  
Transcriptional Landscape

ABSTRACTPhenotypic variability among bacteria depends on gene expression in response to different environments, and it also reflects differences in genomic structure. In this study, we analyzed transcriptome sequencing (RNA-seq) profiles of 151Pseudomonas aeruginosaclinical isolates under standard laboratory conditions and of oneP. aeruginosatype strain under 14 different environmental conditions. Our approach allowed dissection of the impact of the genetic background versus environmental cues onP. aeruginosagene expression profiles and revealed that phenotypic variation was larger in response to changing environments than between genomically different isolates. We demonstrate that mutations within the global regulator LasR affect more than one trait (pleiotropy) and that the interaction between mutations (epistasis) shapes theP. aeruginosaphenotypic plasticity landscape. Because of pleiotropic and epistatic effects, average genotype and phenotype measures appeared to be uncorrelated inP. aeruginosa.IMPORTANCEThis work links experimental data of unprecedented complexity with evolution theory and delineates the transcriptional landscape of the opportunistic pathogenPseudomonas aeruginosa. We found that gene expression profiles are most strongly influenced by environmental cues, while at the same time the transcriptional profiles were also shaped considerably by genetic variation within global regulators. The comprehensive set of transcriptomic and genomic data of more than 150 clinicalP. aeruginosaisolates will be made publically accessible to all researchers via a dedicated web interface. BothPseudomonasspecialists interested in expression and regulation of specific genes and researchers from other fields with more global interest in the phenotypic and genotypic variation of this important model species can access all information on various levels of detail.

scholarly journals Exogenous Alginate Protects Staphylococcus aureus from Killing by Pseudomonas aeruginosa

2019 ◽  
Vol 202 (8) ◽  
Author(s):  
Courtney E. Price ◽  
Dustin G. Brown ◽  
Dominique H. Limoli ◽  
Vanessa V. Phelan ◽  
George A. O’Toole
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Physical Space ◽  
Late Time ◽  
Protective Effects ◽  
Content Type ◽  
Alginate Production ◽  
The Impact

ABSTRACT Cystic fibrosis (CF) patients chronically infected with both Pseudomonas aeruginosa and Staphylococcus aureus have worse health outcomes than patients who are monoinfected with either P. aeruginosa or S. aureus. We showed previously that mucoid strains of P. aeruginosa can coexist with S. aureus in vitro due to the transcriptional downregulation of several toxic exoproducts typically produced by P. aeruginosa, including siderophores, rhamnolipids, and HQNO (2-heptyl-4-hydroxyquinoline N-oxide). Here, we demonstrate that exogenous alginate protects S. aureus from P. aeruginosa in both planktonic and biofilm coculture models under a variety of nutritional conditions. S. aureus protection in the presence of exogenous alginate is due to the transcriptional downregulation of pvdA, a gene required for the production of the iron-scavenging siderophore pyoverdine as well as the downregulation of the PQS (Pseudomonas quinolone signal) (2-heptyl-3,4-dihydroxyquinoline) quorum sensing system. The impact of exogenous alginate is independent of endogenous alginate production. We further demonstrate that coculture of mucoid P. aeruginosa with nonmucoid P. aeruginosa strains can mitigate the killing of S. aureus by the nonmucoid strain of P. aeruginosa, indicating that the mechanism that we describe here may function in vivo in the context of mixed infections. Finally, we investigated a panel of mucoid clinical isolates that retain the ability to kill S. aureus at late time points and show that each strain has a unique expression profile, indicating that mucoid isolates can overcome the S. aureus-protective effects of mucoidy in a strain-specific manner. IMPORTANCE CF patients are chronically infected by polymicrobial communities. The two dominant bacterial pathogens that infect the lungs of CF patients are P. aeruginosa and S. aureus, with ∼30% of patients coinfected by both species. Such coinfected individuals have worse outcomes than monoinfected patients, and both species persist within the same physical space. A variety of host and environmental factors have been demonstrated to promote P. aeruginosa-S. aureus coexistence, despite evidence that P. aeruginosa kills S. aureus when these organisms are cocultured in vitro. Thus, a better understanding of P. aeruginosa-S. aureus interactions, particularly mechanisms by which these microorganisms are able to coexist in proximal physical space, will lead to better-informed treatments for chronic polymicrobial infections.

scholarly journals Immunization with Pneumococcal Polysaccharide Serotype 3 and Lipopolysaccharide Modulates Lung and Liver Inflammation during a Virulent Streptococcus pneumoniae Infection in Mice

2013 ◽  
Vol 20 (5) ◽  
pp. 639-650 ◽  
Author(s):  
Katherine H. Restori ◽  
Mary J. Kennett ◽  
A. Catharine Ross
Keyword(s):  
Gene Expression ◽  
Streptococcus Pneumoniae ◽  
Acute Phase ◽  
Acute Phase Proteins ◽  
Expression Profiles ◽  
Cytokine Gene Expression ◽  
Dependent Manner ◽  
Pneumonia Severity ◽  
Content Type ◽  
Amyloid A

ABSTRACTVaccination reduces morbidity and mortality from pneumonia, but its effect on the tissue-level response to infection is still poorly understood. We evaluated pneumonia disease progression, acute-phase response, and lung gene expression profiles in mice inoculated intranasally with virulent Gram-positiveStreptococcus pneumoniaeserotype 3 (ST 3) with and without prior immunization with pneumococcal polysaccharide ST 3 (PPS3) or after coimmunization with PPS3 and a low dose of lipopolysaccharide (PPS3+LPS). Pneumonia severity was assessed in the acute phase at 5, 12, 24 and 48 h postinoculation (p.i.) and in the resolution phase at 7 days p.i. Primary PPS3-specific antibody production was upregulated, and IgM binding to pneumococci increased in PPS3-immunized mice. Immunizations with PPS3 or PPS3+LPS decreased bacterial recovery in the lung and blood at 24 and 48 h and increased survival. Microarray analysis of whole-lung RNA revealed significant changes in the acute-phase protein serum amyloid A (SAA) levels between noninfected and infected mice, and these changes were attenuated by immunization. SAA transcripts were higher in the liver and lungs of infected controls, and SAA protein was elevated in serum but decreased in PPS3-immunized mice. Thus, during a virulent pneumonia infection, prior immunization with PPS3 in an IgM-dependent manner as well as immunization with PPS3+LPS attenuated pneumonia severity and promoted resolution of infection, concomitant with significant regulation of cytokine gene expression levels in the lungs and acute-phase proteins in the lungs, liver, and serum.

scholarly journals Draft Genome Sequence of the Community-Associated Staphylococcus aureus Sequence Type 88 Strain LVP-7, Isolated from an Ocular Infection

2021 ◽  
Vol 10 (7) ◽  
Author(s):  
Savitha Nadig ◽  
Sneha Murthy ◽  
Muralidharan Vandanashree ◽  
Hosahalli S. Subramanya ◽  
Balasubramanian Gopal ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Genome Sequence ◽  
De Novo ◽  
Draft Genome ◽  
Sequence Type ◽  
Draft Genome Sequence ◽  
Ocular Infection ◽  
Content Type ◽  
Type V ◽  
Panton Valentine Leukocidin

ABSTRACT We report a de novo-assembled draft genome sequence of the Indian Staphylococcus aureus sequence type 88 (ST88) strain LVP-7, isolated from an ocular infection. The genome harbors a Panton-Valentine leukocidin phage, a type V staphylococcal cassette chromosome mec element, the delta-hemolysin-converting Newman phage ΦNM3, and the pathogenicity island SaPI3, encoding the superantigen enterotoxin B.

scholarly journals Transcriptomic Modification in the Cerebral Cortex following Noninvasive Brain Stimulation: RNA-Sequencing Approach

2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
Ben Holmes ◽  
Seung Ho Jung ◽  
Jing Lu ◽  
Jessica A. Wagner ◽  
Liudmilla Rubbi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cerebral Cortex ◽  
Rna Sequencing ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Current Intensity ◽  
Beneficial Effects ◽  
Group A ◽  
The Impact

Transcranial direct current stimulation (tDCS) has been shown to modulate neuroplasticity. Beneficial effects are observed in patients with psychiatric disorders and enhancement of brain performance in healthy individuals has been observed following tDCS. However, few studies have attempted to elucidate the underlying molecular mechanisms of tDCS in the brain. This study was conducted to assess the impact of tDCS on gene expression within the rat cerebral cortex. Anodal tDCS was applied at 3 different intensities followed by RNA-sequencing and analysis. In each current intensity, approximately 1,000 genes demonstrated statistically significant differences compared to the sham group. A variety of functional pathways, biological processes, and molecular categories were found to be modified by tDCS. The impact of tDCS on gene expression was dependent on current intensity. Results show that inflammatory pathways, antidepressant-related pathways (GTP signaling, calcium ion binding, and transmembrane/signal peptide pathways), and receptor signaling pathways (serotonergic, adrenergic, GABAergic, dopaminergic, and glutamate) were most affected. Of the gene expression profiles induced by tDCS, some changes were observed across multiple current intensities while other changes were unique to a single stimulation intensity. This study demonstrates that tDCS can modify the expression profile of various genes in the cerebral cortex and that these tDCS-induced alterations are dependent on the current intensity applied.

scholarly journals Impact of Vitamin B12on Formation of the Tetrachloroethene Reductive Dehalogenase in Desulfitobacterium hafniense Strain Y51

2012 ◽  
Vol 78 (22) ◽  
pp. 8025-8032 ◽  
Author(s):  
Anika Reinhold ◽  
Martin Westermann ◽  
Jana Seifert ◽  
Martin von Bergen ◽  
Torsten Schubert ◽  
...  
Keyword(s):  
Gene Cluster ◽  
De Novo ◽  
Anaerobic Bacteria ◽  
Vitamin B ◽  
Content Type ◽  
Reductive Dehalogenase ◽  
Gene Level ◽  
Desulfitobacterium Hafniense ◽  
Pce Dehalogenase ◽  
The Impact

ABSTRACTCorrinoids are essential cofactors of reductive dehalogenases in anaerobic bacteria. Microorganisms mediating reductive dechlorination as part of their energy metabolism are either capable ofde novocorrinoid biosynthesis (e.g.,Desulfitobacteriumspp.) or dependent on exogenous vitamin B12(e.g.,Dehalococcoidesspp.). In this study, the impact of exogenous vitamin B12(cyanocobalamin) and of tetrachloroethene (PCE) on the synthesis and the subcellular localization of the reductive PCE dehalogenase was investigated in the Gram-positiveDesulfitobacterium hafniensestrain Y51, a bacterium able to synthesize corrinoidsde novo. PCE-depleted cells grown for several subcultivation steps on fumarate as an alternative electron acceptor lost the tetrachloroethene-reductive dehalogenase (PceA) activity by the transposition of thepcegene cluster. In the absence of vitamin B12, a gradual decrease of the PceA activity and protein amount was observed; after 5 subcultivation steps with 10% inoculum, more than 90% of the enzyme activity and of the PceA protein was lost. In the presence of vitamin B12, a significant delay in the decrease of the PceA activity with an ∼90% loss after 20 subcultivation steps was observed. This corresponded to the decrease in thepceAgene level, indicating that exogenous vitamin B12hampered the transposition of thepcegene cluster. In the absence or presence of exogenous vitamin B12, the intracellular corrinoid level decreased in fumarate-grown cells and the PceA precursor formed catalytically inactive, corrinoid-free multiprotein aggregates. The data indicate that exogenous vitamin B12is not incorporated into the PceA precursor, even though it affects the transposition of thepcegene cluster.

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