Ontology highlight
ABSTRACT:
PROVIDER: PRJNA449265 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6996022_1.fastq.gz | Fastqsanger.gz | |||
| SRR6996022_2.fastq.gz | Fastqsanger.gz |
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Project description:Staphylococcus aureus thymidine-dependent small-colony variants (TD-SCVs) are frequently isolated from patients with chronic S. aureus infections after long-term treatment with trimethoprim-sulfamethoxazole (TMP-SMX). In TD-SCVs, mutations of thymidylate synthase (thyA, TS), essential for DNA synthesis, occur. However, it has never been shown, that TMP-SMX is responsible for the induction and selection of TD-SCVs. Short-term exposure of TMP-SMX induced the TD-SCV phenotype morphologically as shown in transmission electron-microscopy and on the transcriptional level by qRT-PCR in wild-type S. aureus, while selection of TD-SCVs with thyA mutations occurred only rarely after long-term exposure. In reversion experiments with clinical TD-SCVs, all revertants revealed compensating mutations at the initially identified mutation site. Whole DNA microarray analysis of a thyA deletion mutant (∆thyA), which exhibited the typical TD-SCV phenotype, identified tremendous alterations compared to the wild-type. Important virulence regulators such as agr, arlRS, sarA and major virulence determinants including hla, hlb, sspA, sspB and geh were down-regulated, while genes associated with the colonization capacity like fnbA, fnbB, spa, clfB, sdrC and sdrD were up-regulated. The expression of genes involved in pyrimidine and purine metabolism as well as in nucleotide interconversion changed significantly. The ∆thyA-mutant was attenuated in virulence in both, a Caenorhabditis elegans killing model and an acute murine pneumonia model. Furthermore, competition experiments in vitro and in vivo (using a chronic pneumonia mouse model) revealed a survival and growth advantage of the ∆thyA-mutant under low thymidine conditions and TMP-SMX exposure. In conclusion, our results clearly show for the first time that TMP-SMX induces the TD-SCV phenotype after short-term exposure in S. aureus and that long-term exposure selects thyA mutations providing an advantage for TD-SCVs under specified conditions. Thus, our results help to understand the dynamic processes of induction and selection of S. aureus TD-SCVs during TMP-SMX exposure.
2013-05-29 | GSE47406 | GEO
Project description:Staphylococcus aureus thymidine-dependent small-colony variants (TD-SCVs) are frequently isolated from patients with chronic S. aureus infections after long-term treatment with trimethoprim-sulfamethoxazole (TMP-SMX). In TD-SCVs, mutations of thymidylate synthase (thyA, TS), essential for DNA synthesis, occur. However, it has never been shown, that TMP-SMX is responsible for the induction and selection of TD-SCVs. Short-term exposure of TMP-SMX induced the TD-SCV phenotype morphologically as shown in transmission electron-microscopy and on the transcriptional level by qRT-PCR in wild-type S. aureus, while selection of TD-SCVs with thyA mutations occurred only rarely after long-term exposure. In reversion experiments with clinical TD-SCVs, all revertants revealed compensating mutations at the initially identified mutation site. Whole DNA microarray analysis of a thyA deletion mutant (M-bM-^HM-^FthyA), which exhibited the typical TD-SCV phenotype, identified tremendous alterations compared to the wild-type. Important virulence regulators such as agr, arlRS, sarA and major virulence determinants including hla, hlb, sspA, sspB and geh were down-regulated, while genes associated with the colonization capacity like fnbA, fnbB, spa, clfB, sdrC and sdrD were up-regulated. The expression of genes involved in pyrimidine and purine metabolism as well as in nucleotide interconversion changed significantly. The M-bM-^HM-^FthyA-mutant was attenuated in virulence in both, a Caenorhabditis elegans killing model and an acute murine pneumonia model. Furthermore, competition experiments in vitro and in vivo (using a chronic pneumonia mouse model) revealed a survival and growth advantage of the M-bM-^HM-^FthyA-mutant under low thymidine conditions and TMP-SMX exposure. In conclusion, our results clearly show for the first time that TMP-SMX induces the TD-SCV phenotype after short-term exposure in S. aureus and that long-term exposure selects thyA mutations providing an advantage for TD-SCVs under specified conditions. Thus, our results help to understand the dynamic processes of induction and selection of S. aureus TD-SCVs during TMP-SMX exposure. 18 independent samples were analysed; for each isolate and time point 3 replicates were performed
2013-05-29 | E-GEOD-47406 | biostudies-arrayexpress
Project description:Background: Prenatal alcohol exposure (PAE) is associated with alterations in numerous physiological systems, including the stress and immune systems. We have previously shown that PAE increases the course and severity of arthritis in an adjuvant-induced arthritis (AA) model. While the molecular mechanisms underlying these effects are not fully known, changes in neural gene expression are emerging as important factors in the etiology of PAE effects. As the prefrontal cortex (PFC) and hippocampus (HPC) play key roles in neuroimmune function, PAE-induced alterations to their transcriptome may underlie abnormal steady-state functions and responses to immune challenge. The current study examined brains from adult PAE and control females from our recent AA study to determine whether PAE causes long-term alterations in gene expression and whether these mediate the altered severity and course of arthritis in PAE females Methods: Adult females from PAE, pair-fed [PF], and ad libitum-fed control [C]) groups were injected with either saline or complete FreundM-bM-^@M-^Ys adjuvant. Animals were terminated at the peak of inflammation or during resolution (days 16 and 39 post-injection, respectively); cohorts of saline-injected PAE, PF and C females were terminated in parallel. Gene expression was analyzed in the PFC and HPC using whole genome mRNA expression microarrays. Results: Significant changes in gene expression in both the PFC and HPC were found in PAE compared to controls in response to ethanol exposure alone (saline-injected females), including genes involved in neurodevelopment, apoptosis, and energy metabolism. Moreover, in response to inflammation (adjuvant-injected females), PAE animals showed unique expression patterns, while failing to exhibit the activation of genes and regulators involved in the immune response observed in control and pair-fed animals. Conclusions: These results support the hypothesis that PAE affects neuroimmune function at the level of gene expression, demonstrating long-term effects of PAE on the CNS response under steady-state conditions and following an inflammatory insult. Key words: prenatal alcohol exposure (PAE), ethanol, inflammation, arthritis, gene expression, rat. 192 samples, including 20 hybridization replicates
2014-11-21 | E-GEOD-63561 | biostudies-arrayexpress
Project description:A chemical screen was performed in search of compounds that modify plant responses to sucrose. This screen uncovered that sulfamethoxazole (SMX), a folate biosynthesis inhibitor, acted synergistically with sucrose to inhibit hypocotyl elongation, suggesting interaction between these two pathways. Transcriptome analysis was performed to identify changes in transcript abundance that may underpin crosstalk between sucrose and SMX. Three-day-old dark-grown seedlings were treated to sucrose and SMX at concentrations that induced no change in hypocotyl elongation when administered independently, yet restricted elongation when both were present in the growth media (10mM and 0.2µM, respectively). This analysis uncovered multiple core auxin signalling components that exhibit altered transcript abundance in response to co-treatment with sucrose and SMX, suggesting that auxin signalling mediates crosstalk between these two pathways. This study highlights an input through which metabolic status can shape plant growth and development through hormone signalling. 12 arrays total. Three arrays as non-treated control, three arrays from seedlings raised in presence of 0.2µM SMX, three arrays from seedlings raised in presence of 10mM sucrose, and three arrays from seeldings raised in presence of both 10mM sucrose and 0.2µM SMX. Three biological replicates were produced for each growth treatment.
2013-06-30 | E-GEOD-37484 | biostudies-arrayexpress
Project description:Potentiated sulfonamide antibiotics such as trimethoprim/sulfamethoxazole (cotrimoxazole or TMP/SMX) remain the drugs of choice for treatment and prevention of Pneumocystis jiroveci pneumonia, toxoplasma encephalitis, and Isospora infections in HIV infection (aidsinfo.nih.gov). However, HIV-infected patients show a markedly increased risk of delayed hypersensitivity (HS) reactions to TMP/SMX (20-57% incidence) when compared to the general population (3% incidence). The typical manifestation is maculopapular rash with or without fever, and TMP/SMX is the most common cause of cutaneous drug reactions in HIV-infected patients TMP/SMX can also lead to thrombocytopenia, hepatotoxicity, and bullous skin eruptions in more severely affected patients. The risk of sulfonamide HS increases with progression to AIDS, with higher risk seen at lower CD4+ counts. This risk has been attributed, at least in part, to acquired alterations in SMX drug disposition in HIV infection. We hypothesized that HIV infection leads to impaired hepatic SMX detoxification or enhanced SMX bioactivation pathways, which may contribute to the increased incidence of sulfonamide HS. We addressed this question using liver tissue from SIVmac239-infected macaques, a well accepted model of HIV infection. The aim of this study was to evaluate differences in the hepatic expression and activity of SMX biotransformation pathways from drug naïve SIV-infected macaques compared to sex- and age-matched uninfected controls.
2017-07-11 | GSE87158 | GEO
Project description:Previous research has linked perceived social isolation (loneliness) to reduced antiviral immunity, but the immunologic effects of the objective social isolation imposed by pandemic “shelter in place” (SIP) policies is unknown. We assessed the immunologic impact of SIP by relocating 21 adult male rhesus macaques from 2000 sq-m field cage communities of 70-132 other macaques to 2 wks of individual housing in indoor shelters. SIP was associated with down-regulation of Type I interferon (IFN) antiviral gene expression. This effect emerged within the first 48 hrs of SIP, persisted for at least 2 wks, and abated within 4 wks of return to social housing. A subsequent round of SIP in the presence of a novel juvenile macaque abrogated this effect. These results identify a significant adverse effect of SIP social isolation on antiviral immune regulation in circulating immune cells and they suggest a potential behavioral strategy for ameliorating such effects by promoting pro-social engagement during SIP.
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