Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Streptococcus agalactiae genes controlled by the MtaR transcription factor

ABSTRACT: The purpose of this study was to determine what S. agalactiae genes are under the control of the MtaR regulatory protein. Inactivation of the Streptococcus agalactiae mtaR gene resulted in the downregulation of 11 genes and the upregulation of 1 gene in the mtaR mutant. Genes involved in the uptake of methionine and a gene involved in the degradation of peptides were downregulated. Also, genes involved in the transport and biosynthesis of arginine were downregulated. The gene encoding the virulence factor cspA was downregulated, as well as a gene showing similarity to plasminogen activators. Thus, the expression of genes involved in both metabolic functions and virulence are under the influence of mtaR. Three cultures of an mtaR insertional mutant (DS101) and three cultures of the isogenic wild-type strain (COH1) were grown in a chemically-defined medium. Cells were disrupted with glass-bead and RNA was isolated by a Trizol method. A custom Affymetrix chip was utilized for microarray analysis. Genes were considered differentially-expressed if they showed a >2.0-fold difference in expression between the strains and a Bayesian (Cyber-T) t-test value of <0.001. The posterior probability of differential expression (PPDE) (< p) value for the genes identified was >0.964.

ORGANISM(S): Streptococcus agalactiae

SUBMITTER: Daniel Shelver

PROVIDER: E-GEOD-13325 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Global transcriptional profiling reveals Streptococcus agalactiae genes controlled by the MtaR transcription factor.

Bryan Joshua D JD Liles Roxanne R Cvek Urska U Trutschl Marjan M Shelver Daniel D

BMC genomics 20081216

<h4>Background</h4>Streptococcus agalactiae (group B Streptococcus; GBS) is a significant bacterial pathogen of neonates and an emerging pathogen of adults. Though transcriptional regulators are abundantly encoded on the GBS genome, their role in GBS pathogenesis is poorly understood. The mtaR gene encodes a putative LysR-type transcriptional regulator that is critical for the full virulence of GBS. Previous studies have shown that an mtaR- mutant transports methionine at reduced rates and grows ...[more]

PMID: 19087320

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Project description:Objective : To study molecular changes in the articular cartilage and subchondral bone of the tibial plateau from mice deficient in frizzled related protein (Frzb) compared to wild-type mice by transcriptome analysis. Methods : Gene-expression analysis of the articular cartilage and subchondral bone of 3 wild-type and 3 Frzb-/- mice was performed by microarray. Pathway analysis of differentially expressed genes between 3 wild-type and 2 Frzb-/- samples was explored with PANTHER, DAVID and GSEA bioinformatics tools. Activation of the WNT pathway was analyzed using western blot. The effects of Frzb gain and loss of function on chondrogenesis and cell proliferation was examined using ATDC5 micromasses and mouse ribcage chondrocytes. Results : Extracellular matrix-associated integrin and cadherin pathways, as well as WNT pathway genes were upregulated in Frzb-/- samples. Several WNT receptors, target genes, and other antagonists were upregulated, but no difference in active β-catenin was found. Analysis of ATDC5 cell micromasses overexpressing FRZB indicated an upregulation of aggrecan and Col2a1, and downregulation of molecules related to damage and repair in cartilage, Col3a1 and Col5a1. Silencing of Frzb resulted in downregulation of aggrecan and Col2a1. Pathways associated with cell cycle were downregulated. Ribcage chondrocytes derived from Frzb-/- mice showed decreased proliferation compared to wild-type cells. Conclusions : Our analysis provides evidence for tight regulation of WNT signaling, shifts in extracellular matrix components and effects on cell proliferation and differentiation in the articular cartilage - subchondral bone unit in Frzb-/- mice. These data further support an important role for FRZB in joint homeostasis and highlight the complex biology of WNT signaling in the joint. Gene-expression analysis of the articular cartilage and subchondral bone of 3 wild-type and 3 Frzb-/- mice was performed by microarray. Pathway analysis of differentially expressed genes between 3 wild-type and 2 Frzb-/- samples was explored with PANTHER, DAVID and GSEA bioinformatics tools.

Project description:Objectives: Development of daptomycin resistance (DAPR) in Staphylococcus aureus is associated with clinical treatment failures. Mechanism(s) of such resistance has not been clearly defined. Methods: We studied an isogenic daptomycin-susceptible (DAPS) and daptomycin-resistant (DAPR) S. aureus strain pair (616; 701) from a patient with relapsing endocarditis during daptomycin treatment, using comparative transcriptomic and proteomic techniques. Results. Minor differences in genome content were found between strains by DNA hybridization. Transcriptomic analyses identified a number of genes differentially expressed in important functional categories: cell division, metabolism of bacterial envelopes and global regulation. Of note, the DAPR isolate exhibited reduced expression of the major cell wall autolysis gene coincident with upregulation of genes involved in wall teichoic acid production. Using quantitative (q)RT-PCR on gene cadre putatively involved in cationic peptide resistance, we formulated a putative regulatory network compatible with microarray data-sets, mainly implicating bacterial envelopes. Of interest, qRT-PCR of this same gene cadre from two distinct isogenic DAPS/DAPR clinical strain pairs revealed evidence of other strain dependent networks operative in the DAPR phenotype. Comparative proteomics of 616 vs 701 revealed differential abundance of proteins in various functional categories including: cell-wall associated targets and biofilm-formation proteins. Phenotypically, strains 616 and 701 showed major differences in ability to develop bacterial biofilms in presence of the antibacterial lipid, oleic acid. Conclusions: Compatible with previous in vitro observations, in vivo acquired DAPR in S. aureus is a complex, multistep phenomenon allowing for: i) strain dependent phenotypes; ii) transcriptome adaptation; and iii) modification of lipid and protein content of cellular envelopes. Daptomycin suceptible strain vs daptomycin non suceptible strain after daptomycin treatment

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Streptococcus agalactiae genes controlled by the MtaR transcription factor

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Global transcriptional profiling reveals Streptococcus agalactiae genes controlled by the MtaR transcription factor.

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