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 Comparative Transcriptomic Profiling ofYersinia enterocoliticaO:3 and O:8 Reveals Major Expression Differences of Fitness- and Virulence-Relevant Genes Indicating Ecological Separation

mSystems ◽  
2019 ◽  
Vol 4 (2) ◽  
Author(s):  
Carina Schmühl ◽  
Michael Beckstette ◽  
Ann Kathrin Heroven ◽  
Boyke Bunk ◽  
Cathrin Spröer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Yersinia Enterocolitica ◽  
Dna Sequences ◽  
Expression Profiles ◽  
Bacterial Species ◽  
Comparative Transcriptomics ◽  
Gastrointestinal Infections ◽  
Content Type ◽  
Serotype O ◽  
Ecological Separation

ABSTRACTYersinia enterocoliticais a zoonotic pathogen and an important cause of bacterial gastrointestinal infections in humans. Large-scale population genomic analyses revealed genetic and phenotypic diversity of this bacterial species, but little is known about the differences in the transcriptome organization, small RNA (sRNA) repertoire, and transcriptional output. Here, we present the first comparative high-resolution transcriptome analysis ofY. enterocoliticastrains representing highly pathogenic phylogroup 2 (serotype O:8) and moderately pathogenic phylogroup 3 (serotype O:3) grown under four infection-relevant conditions. Our transcriptome sequencing (RNA-seq) approach revealed 1,299 and 1,076 transcriptional start sites and identified strain-specific sRNAs that could contribute to differential regulation among the phylogroups. Comparative transcriptomics further uncovered major gene expression differences, in particular, in the temperature-responsive regulon. Multiple virulence-relevant genes are differentially regulated between the two strains, supporting an ecological separation of phylogroups with certain niche-adapted properties. Strong upregulation of theystAenterotoxin gene in combination with constitutive high expression of cell invasion factor InvA further showed that the toxicity of recent outbreak O:3 strains has increased. Overall, our report provides new insights into the specific transcriptome organization of phylogroups 2 and 3 and reveals gene expression differences contributing to the substantial phenotypic differences that exist between the lineages.IMPORTANCEYersinia enterocoliticais a major diarrheal pathogen and is associated with a large range of gut-associated diseases. Members of this species have evolved into different phylogroups with genotypic variations. We performed the first characterization of theY. enterocoliticatranscriptional landscape and tracked the consequences of the genomic variations between two different pathogenic phylogroups by comparing their RNA repertoire, promoter usage, and expression profiles under four different virulence-relevant conditions. Our analysis revealed major differences in the transcriptional outputs of the closely related strains, pointing to an ecological separation in which one is more adapted to an environmental lifestyle and the other to a mostly mammal-associated lifestyle. Moreover, a variety of pathoadaptive alterations, including alterations in acid resistance genes, colonization factors, and toxins, were identified which affect virulence and host specificity. This illustrates that comparative transcriptomics is an excellent approach to discover differences in the functional output from closely related genomes affecting niche adaptation and virulence, which cannot be directly inferred from DNA sequences.

scholarly journals Analysis of theIn VivoTranscriptome ofBordetella pertussisduring Infection of Mice

mSphere ◽  
2019 ◽  
Vol 4 (2) ◽  
Author(s):  
Ting Y. Wong ◽  
Jesse M. Hall ◽  
Evan S. Nowak ◽  
Dylan T. Boehm ◽  
Laura A. Gonyar ◽  
...  
Keyword(s):  
Gene Expression ◽  
Iron Acquisition ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Growth Conditions ◽  
Rna Seq ◽  
Content Type ◽  
Murine Lung

ABSTRACTBordetella pertussiscauses the disease whooping cough through coordinated control of virulence factors by theBordetellavirulence gene system. Microarrays and, more recently, RNA sequencing (RNA-seq) have been used to describein vitrogene expression profiles ofB. pertussisand other pathogens. In previous studies, we have analyzed thein vitrogene expression profiles ofB. pertussis, and we hypothesize that the infection transcriptome profilein vivois significantly different from that under laboratory growth conditions. To study the infection transcriptome ofB. pertussis, we developed a simple filtration technique for isolation of bacteria from infected lungs. The work flow involves filtering the bacteria out of the lung homogenate using a 5-μm-pore-size syringe filter. The captured bacteria are then lysed to isolate RNA for Illumina library preparation and RNA-seq analysis. Upon comparing thein vitroandin vivogene expression profiles, we identified 351 and 255 genes as activated and repressed, respectively, during murine lung infection. As expected, numerous genes associated with virulent-phase growth were activated in the murine host, including pertussis toxin (PT), the PT secretion apparatus, and the type III secretion system. A significant number of genes encoding iron acquisition and heme uptake proteins were highly expressed during infection, supporting iron acquisition as critical forB. pertussissurvivalin vivo. Numerous metabolic genes were repressed during infection. Overall, these data shed light on the gene expression profile ofB. pertussisduring infection, and this method will facilitate efforts to understand how this pathogen causes infection.IMPORTANCEIn vitrogrowth conditions for bacteria do not fully recapitulate the host environment. RNA sequencing transcriptome analysis allows for the characterization of the infection gene expression profiles of pathogens in complex environments. Isolation of the pathogen from infected tissues is critical because of the large amounts of host RNA present in crude lysates of infected organs. A filtration method was developed that enabled enrichment of the pathogen RNA for RNA-seq analysis. The resulting data describe the “infection transcriptome” ofB. pertussisin the murine lung. This strategy can be utilized for pathogens in other hosts and, thus, expand our knowledge of what bacteria express during infection.

scholarly journals Identification of BvgA-Dependent and BvgA-Independent Small RNAs (sRNAs) in Bordetella pertussis Using the Prokaryotic sRNA Prediction Toolkit ANNOgesic

2021 ◽  
Author(s):  
Kyung Moon ◽  
Minji Sim ◽  
Chin-Hsien Tai ◽  
Kyungyoon Yoo ◽  
Charlotte Merzbacher ◽  
...  
Keyword(s):  
Gene Expression ◽  
Small Rnas ◽  
Posttranscriptional Regulation ◽  
Transcriptome Sequencing ◽  
Regulation Of Gene Expression ◽  
Bacterial Virulence ◽  
Human Pathogen ◽  
Rna Seq ◽  
Content Type ◽  
Search Program

Noncoding small RNAs (sRNAs) are crucial for posttranscriptional regulation of gene expression in all organisms and are known to be involved in the regulation of bacterial virulence. We have investigated the presence of sRNAs in the obligate human pathogen B. pertussis , using transcriptome sequencing (RNA-seq) and the recently developed prokaryotic sRNA search program ANNOgesic.

scholarly journals Host and Parasite Transcriptomic Changes upon Successive Plasmodium falciparum Infections in Early Childhood

mSystems ◽  
2020 ◽  
Vol 5 (4) ◽  
Author(s):  
Katie R. Bradwell ◽  
Drissa Coulibaly ◽  
Abdoulaye K. Koné ◽  
Matthew B. Laurens ◽  
Ahmadou Dembélé ◽  
...  
Keyword(s):  
Gene Expression ◽  
Plasmodium Falciparum ◽  
Expression Profiles ◽  
Severe Disease ◽  
Cell Subset ◽  
Gene Expression Profiles ◽  
Rna Seq ◽  
Blood Samples ◽  
Content Type ◽  
Host Parasite

ABSTRACT Children are highly susceptible to clinical malaria, and in regions where malaria is endemic, their immune systems must face successive encounters with Plasmodium falciparum parasites before they develop immunity, first against severe disease and later against uncomplicated malaria. Understanding cellular and molecular interactions between host and parasites during an infection could provide insights into the processes underlying this gradual acquisition of immunity, as well as to how parasites adapt to infect hosts that are successively more malaria experienced. Here, we describe methods to analyze the host and parasite gene expression profiles generated simultaneously from blood samples collected from five consecutive symptomatic P. falciparum infections in three Malian children. We show that the data generated enable statistical assessment of the proportions of (i) each white blood cell subset and (ii) the parasite developmental stages, as well as investigations of host-parasite gene coexpression. We also use the sequences generated to analyze allelic variations in transcribed regions and determine the complexity of each infection. While limited by the modest sample size, our analyses suggest that host gene expression profiles primarily clustered by individual, while the parasite gene expression profiles seemed to differentiate early from late infections. Overall, this study provides a solid framework to examine the mechanisms underlying acquisition of immunity to malaria infections using whole-blood transcriptome sequencing (RNA-seq). IMPORTANCE We show that dual RNA-seq from patient blood samples allows characterization of host/parasite interactions during malaria infections and can provide a solid framework to study the acquisition of antimalarial immunity, as well as the adaptations of P. falciparum to malaria-experienced hosts.

scholarly journals Reversible Antibiotic Tolerance Induced in Staphylococcus aureus by Concurrent Drug Exposure

mBio ◽  
2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Jakob Haaber ◽  
Cathrine Friberg ◽  
Mark McCreary ◽  
Richard Lin ◽  
Stanley N. Cohen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Staphylococcus Aureus ◽  
Treatment Failure ◽  
Drug Exposure ◽  
Bacterial Species ◽  
Sensitivity Testing ◽  
Genetic Changes ◽  
Clinical Prognosis ◽  
Gram Negative ◽  
Content Type

ABSTRACT  Resistance ofStaphylococcus aureusto beta-lactam antibiotics has led to increasing use of the glycopeptide antibiotic vancomycin as a life-saving treatment for major S. aureus infections. Coinfection by an unrelated bacterial species may necessitate concurrent treatment with a second antibiotic that targets the coinfecting pathogen. While investigating factors that affect bacterial antibiotic sensitivity, we discovered that susceptibility of S. aureus to vancomycin is reduced by concurrent exposure to colistin, a cationic peptide antimicrobial employed to treat infections by Gram-negative pathogens. We show that colistin-induced vancomycin tolerance persists only as long as the inducer is present and is accompanied by gene expression changes similar to those resulting from mutations that produce stably inherited reduction of vancomycin sensitivity (vancomycin-intermediate S. aureus [VISA] strains). As colistin-induced vancomycin tolerance is reversible, it may not be detected by routine sensitivity testing and may be responsible for treatment failure at vancomycin doses expected to be clinically effective based on such routine testing.IMPORTANCE   Commonly, antibiotic resistance is associated with permanent genetic changes, such as point mutations or acquisition of resistance genes. We show that phenotypic resistance can arise where changes in gene expression result in tolerance to an antibiotic without any accompanying genetic changes. Specifically, methicillin-resistantStaphylococcus aureus(MRSA) behaves like vancomycin-intermediate S. aureus (VISA) upon exposure to colistin, which is currently used against infections by Gram-negative bacteria. Vancomycin is a last-resort drug for treatment of serious S. aureus infections, and VISA is associated with poor clinical prognosis. Phenotypic and reversible resistance will not be revealed by standard susceptibility testing and may underlie treatment failure.

scholarly journals Genome-Scale Mapping Reveals Complex Regulatory Activities of RpoN in Yersinia pseudotuberculosis

mSystems ◽  
2020 ◽  
Vol 5 (6) ◽  
Author(s):  
A. K. M. Firoj Mahmud ◽  
Kristina Nilsson ◽  
Anna Fahlgren ◽  
Roberto Navais ◽  
Rajdeep Choudhury ◽  
...  
Keyword(s):  
Gene Expression ◽  
Binding Sites ◽  
Sigma Factor ◽  
Biofilm Formation ◽  
Yersinia Pseudotuberculosis ◽  
Binding Motif ◽  
Alternative Sigma Factor ◽  
Altered Expression ◽  
Content Type ◽  
Sense Strand

ABSTRACT RpoN, an alternative sigma factor commonly known as σ54, is implicated in persistent stages of Yersinia pseudotuberculosis infections in which genes associated with this regulator are upregulated. We here combined phenotypic and genomic assays to provide insight into its role and function in this pathogen. RpoN was found essential for Y. pseudotuberculosis virulence in mice, and in vitro functional assays showed that it controls biofilm formation and motility. Mapping genome-wide associations of Y. pseudotuberculosis RpoN using chromatin immunoprecipitation coupled with next-generation sequencing identified an RpoN binding motif located at 103 inter- and intragenic sites on both sense and antisense strands. Deletion of rpoN had a large impact on gene expression, including downregulation of genes encoding proteins involved in flagellar assembly, chemotaxis, and quorum sensing. There were also clear indications of cross talk with other sigma factors, together with indirect effects due to altered expression of other regulators. Matching differential gene expression with locations of the binding sites implicated around 130 genes or operons potentially activated or repressed by RpoN. Mutagenesis of selected intergenic binding sites confirmed both positive and negative regulatory effects of RpoN binding. Corresponding mutations of intragenic sense sites had less impact on associated gene expression. Surprisingly, mutating intragenic sites on the antisense strand commonly reduced expression of genes carried by the corresponding sense strand. IMPORTANCE The alternative sigma factor RpoN (σ54), which is widely distributed in eubacteria, has been implicated in controlling gene expression of importance for numerous functions including virulence. Proper responses to host environments are crucial for bacteria to establish infection, and regulatory mechanisms involved are therefore of high interest for development of future therapeutics. Little is known about the function of RpoN in the intestinal pathogen Y. pseudotuberculosis, and we therefore investigated its regulatory role in this pathogen. This regulator was indeed found to be critical for establishment of infection in mice, likely involving its requirement for motility and biofilm formation. The RpoN regulon involved both activating and suppressive effects on gene expression which could be confirmed with mutagenesis of identified binding sites. This is the first study of its kind of RpoN in Y. pseudotuberculosis, revealing complex regulation of gene expression involving both productive and silent effects of its binding to DNA, providing important information about RpoN regulation in enterobacteria.

scholarly journals Use of Microfluidic Technology To Analyze Gene Expression during Staphylococcus aureus Biofilm Formation Reveals Distinct Physiological Niches

2013 ◽  
Vol 79 (11) ◽  
pp. 3413-3424 ◽  
Author(s):  
Derek E. Moormeier ◽  
Jennifer L. Endres ◽  
Ethan E. Mann ◽  
Marat R. Sadykov ◽  
Alexander R. Horswill ◽  
...  
Keyword(s):  
Gene Expression ◽  
Staphylococcus Aureus ◽  
Biofilm Formation ◽  
Molecular Mechanisms ◽  
Fluorescent Protein ◽  
Time Lapse ◽  
Microfluidic System ◽  
Fluorescent Reporter ◽  
Content Type ◽  
Biofilm Development

ABSTRACTTheStaphylococcus aureus cidandlrgoperons play significant roles in the control of autolysis and accumulation of extracellular genomic DNA (eDNA) during biofilm development. Although the molecular mechanisms mediating this control are only beginning to be revealed, it is clear that cell death must be limited to a subfraction of the biofilm population. In the present study, we tested the hypothesis thatcidandlrgexpression varies during biofilm development as a function of changes in the availability of oxygen. To examinecidandlrgpromoter activity during biofilm development, fluorescent reporter fusion strains were constructed and grown in a BioFlux microfluidic system, generating time-lapse epifluorescence images of biofilm formation, which allows the spatial and temporal localization of gene expression. Consistent withcidinduction under hypoxic conditions, thecid::gfpfusion strain expressed green fluorescent protein predominantly within the interior of the tower structures, similar to the pattern of expression observed with a strain carrying agfpfusion to the hypoxia-induced promoter controlling the expression of the lactose dehydrogenase gene. Thelrgpromoter was also expressed within towers but appeared more diffuse throughout the tower structures, indicating that it was oxygen independent. Unexpectedly, the results also demonstrated the existence of tower structures with different expression phenotypes and physical characteristics, suggesting that these towers exhibit different metabolic activities. Overall, the findings presented here support a model in which oxygen is important in the spatial and temporal control ofcidexpression within a biofilm and that tower structures formed during biofilm development exhibit metabolically distinct niches.

scholarly journals Overexpression of Genes of the Cell Wall Stimulon in Clinical Isolates of Staphylococcus aureus Exhibiting Vancomycin-Intermediate- S. aureus-Type Resistance to Vancomycin

2006 ◽  
Vol 188 (3) ◽  
pp. 1120-1133 ◽  
Author(s):  
Fionnuala McAleese ◽  
Shang Wei Wu ◽  
Krzysztof Sieradzki ◽  
Paul Dunman ◽  
Ellen Murphy ◽  
...  
Keyword(s):  
Gene Expression ◽  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Heart Valve ◽  
Genetic Relatedness ◽  
Expression Profiles ◽  
Altered Expression ◽  
Vancomycin Mics ◽  
Protein Encoding ◽  
Encoding Genes

ABSTRACT Custom-designed gene chips (Affymetrix) were used to determine genetic relatedness and gene expression profiles in Staphylococcus aureus isolates with increasing MICs of vancomycin that were recovered over a period of several weeks from the blood and heart valve of a patient undergoing extensive vancomycin therapy. The isolates were found to be isogenic as determined by the GeneChip based genotyping approach and thus represented a unique opportunity to study changes in gene expression that may contribute to the vancomycin resistance phenotype. No differences in gene expression were detected between the parent strain, JH1, and JH15, isolated from the nares of a patient contact. Few expression changes were observed between blood and heart valve isolates with identical vancomycin MICs. A large number of genes had altered expression in the late stage JH9 isolate (MIC = 8 μg/ml) compared to JH1 (MIC = 1 μg/ml). Most genes with altered expression were involved in housekeeping functions or cell wall biosynthesis and regulation. The sortase-encoding genes, srtA and srtB, as well as several surface protein-encoding genes were downregulated in JH9. Two hypothetical protein-encoding genes, SAS016 and SA2343, were dramatically overexpressed in JH9. Interestingly, 27 of the genes with altered expression in JH9 grown in drug-free medium were found to be also overexpressed when the parental strain JH1 was briefly exposed to inhibitory concentrations of vancomycin, and more than half (17 of 27) of the genes with altered expression belonged to determinants that were proposed to form part of a general cell wall stress stimulon (S. Utaida et al., Microbiology 149:2719-2732, 2003).

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.

The Oral Intake of Organic Germanium, Ge-132, Elevates α-Tocopherol Levels in the Plas-ma and Modulates Hepatic Gene Expression Profiles to Promote Immune Activation in Mice

2014 ◽  
Vol 84 (3-4) ◽  
pp. 0183-0195 ◽  
Author(s):  
Takashi Nakamura ◽  
Tomoya Takeda ◽  
Yoshihiko Tokuji
Keyword(s):  
Gene Expression ◽  
Immune Activation ◽  
Expression Profiles ◽  
Water Soluble ◽  
Alpha Tocopherol ◽  
Hepatic Gene Expression ◽  
Tocopherol Concentration ◽  
Altered Expression ◽  
Atp Production ◽  
Transfer Protein

The common water-soluble organic germanium compound poly-trans-[(2-carboxyethyl) germasesquioxane] (Ge-132) exhibits activities related to immune responses and antioxidant induction. In this study, we evaluated the antioxidative effect of dietary Ge-132 in the plasma of mice. Male ICR mice (seven mice per group) received an AIN-76 diet with 0.05 % Ge-132; three groups received the Ge-132-containing diet for 0, 1 or 4 days. The plasma alpha-tocopherol (α-tocopherol) concentration increased from 6.85 to 9.60 μg/ml after 4 days of Ge-132 intake (p < 0.05). We evaluated the changes in hepatic gene expression related to antioxidative activity as well as in the entire expression profile after one day of Ge-132 intake, using DNA microarray technology. We identified 1,220 genes with altered expression levels greater than 1.5-fold (increased or decreased) as a result of Ge-132 intake, and α-tocopherol transfer protein (Ttpa) gene expression was increased 1.62-fold. Immune activation was identified as the category with the most changes (containing 60 Gene Ontology (GO) term biological processes (BPs), 41 genes) via functional clustering analysis of altered gene expression. Ge-132 affected genes in clusters related to ATP production (22 GO term BPs, 21 genes), lipid metabolism (4 GO term BPs, 38 genes) and apoptosis (5 GO term BPs). Many GO term BPs containing these categories were significantly affected by the Ge-132 intake. Oral Ge-132 intake may therefore have increased plasma α-tocopherol levels by up-regulating α-tocopherol transfer protein (Ttpa) gene expression.

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