Staphylococcus aureus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA268968 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR1686734.fastq.gz | Fastqsanger.gz | |||
| SRR1686735.fastq.gz | Fastqsanger.gz | |||
| SRR1686736.fastq.gz | Fastqsanger.gz | |||
| SRR2079245_subreads.fastq.gz | Fastqsanger.gz | |||
| SRR2079246_subreads.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Transcriptional profiling of the small colony variant (SCV) S. aureus isolate (JKD6229) compared to the parent isolate with a normal phenotype (JKD6210). Both isolates were from a patient with persistent S. aureus infection, and the SCV strain arose during failed antibiotic therapy.
2010-08-13 | GSE20957 | GEO
Project description:Transcriptional profiling of the small colony variant (SCV) S. aureus isolate (JKD6229) compared to the parent isolate with a normal phenotype (JKD6210). Both isolates were from a patient with persistent S. aureus infection, and the SCV strain arose during failed antibiotic therapy. Two condition experiment JKD6229 vs JKD6210. 4 biological replicates, one replicate per slide.
2010-08-13 | E-GEOD-20957 | biostudies-arrayexpress
Project description:We have observed that for a number of S. aureus strains as they switch to a SCV lifestyle there is the formation of an extracellular matrix. We focused our analysis on one strain, WCH-SK2. For bacterial survival in the host, the combination of low nutrients and the prolonged timeframe forms a stress that selects for a specific cell-type from the population. In this context, we used steady-state growth conditions with low nutrients and a controlled low growth rate, for a prolonged time and with methylglyoxal. These conditions induced S. aureus WCH-SK2 into a stable SCV cell-type, they did not revert after sub-culturing. Methods: Transcriptomic profiles of wild-type (WT) and SCV were generated in continuous culture in the presence of stress (high and low level of methylglyoxal). Results: Analysis revealed these cells possessed a metabolic and surface profile that was different from previously described SCVs or biofilm cells. The extracellular matrix was protein and extracellular DNA; but not polysaccharide. The SCV cells induced expression of certain surface proteins (such as Ebh) and lantibiotic synthesis while down-regulating factors that stimulates immune response (leucocidin, capsule, carotenoid). We also studied further their genetic characteristics. They possessed an increased viability in the presence of antibiotics compared to their non-SCV form. Their stability implied there had been genetic changes, we determined the whole genome sequence of WCH-SK2 and its stable SCV forms at a single base resolution, employing Single Molecular Real-Time (SMRT) sequencing that also enables the methylome to be determined. The genetic features of this isolate have been identified; the SCCmec type, the pathogenicity and genetic islands and virulence factors. The comparison has identified a set of genetic changes that occurred in the stable SCV form; most notably to the global regulator MgrA and the phosphoserine phosphatase RsbU (part of the regulatory pathway of the sigma factor SigB). There was a shift in the methylation across the genome. Conclusions: Our data reveal a cell heterogeneity within a S. aureus population and using conditions that resemble long-term survival in the host has identified a previously unnoticed S. aureus cell-type, with a distinctive metabolic and molecular profile. The results from this study represent a unique identification of a suite of epigenetic, genetic and transcriptional factors that are implicated in the switch in S. aureus to its persistent SCV form
2014-12-02 | GSE63750 | GEO
Project description:Respiration deficient S. aureus small colony variants (SCVs) frequently cause persistent infections, which necessitates they acquire iron, yet how SCVs obtain iron remains unknown. To address this, we created a stable hemB mutant in S. aureus USA300 strain LAC. The hemB SCV utilized exogenously supplied heme but was attenuated for growth under conditions of iron starvation. RNA-seq showed that both WT S. aureus and the hemB mutant sense and respond to iron starvation.
2022-09-06 | GSE184082 | GEO
Project description:<p>Antibiotic treatment failure in Staphylococcus aureus infections is frequently associated with antimicrobial resistance or the emergence of small-colony variants (SCVs), a metabolically quiescent phenotype that complicates infection management. Here, we show that ciprofloxacin induces a stable SCV phenotype in S. aureus, characterized by reduced colony size, impaired growth, attenuated virulence, and prolonged persistence. Integrated genomic, transcriptomic, and metabolomic analyses revealed that ciprofloxacin-induced SCVs harbor a tal (transaldolase) mutation, which disrupts glycolytic and pentose phosphate pathway flux, depleting pyruvate and tricarboxylic acid cycle intermediates and collapsing ATP biosynthesis. This metabolic disruption leads to nutrient stress and energy limitation, further compounded by a relA mutation that elevates (p)ppGpp accumulation and activates the stringent response. The combined effects of tal- and relA-mediated reprogramming drive metabolic quiescence and the SCV state. Notably, ciprofloxacin-induced SCVs exhibited collateral sensitivity to aminoglycosides both in vitro and in vivo, suggesting that metabolic trade-offs accompanying the stringent response could be therapeutically exploited. These findings define how ciprofloxacin-induced metabolic disruption and stringent response activation cooperatively drive persistent SCV formation in S. aureus, providing new opportunities to overcome antibiotic persistence.</p>
2025-11-19 | MTBLS13343 | MetaboLights
Project description:In this study we have profiled a clinical tobramycin resistant P. aeruginosa strain that exhibited a small colony variant (SCV) phenotype. Both, the resistance and the colony morphology phenotypes were lost upon passaging the isolate under rich medium conditions. Transcriptional and mutational profiling revealed that the SCV harbored activating mutations in the two two-component systems AmgRS and PmrAB. Introduction of these mutations singularly into the type strain PA14 conferred tobramycin and colistin resistance, respectively. However, their combined introduction had an additive effect on the tobramycin resistance phenotype. Activation of the AmgRS system slightly reduced the colony size of the PA14 wild-type, whereas the simultaneous overexpression of gacA, the response regulator of the GacSA two component system, further reduced colony size. In conclusion, we uncovered combinatorial influences of two-component systems on clinically relevant phenotypes, such as resistance and the expression of the SCV phenotype. Our results clearly demonstrate that combined activation of P. aeruginosa two-component systems exhibit pleiotropic effects with unforeseen consequences.
2017-08-22 | GSE99729 | GEO
Project description:Staphylococcus aureus small colony variants (SCVs) are metabolically adapted, slow-growing subpopulations responsible for chronic, recurrent bovine mastitis through enhanced intracellular persistence and immune evasion. The role of Toll-like receptor 4 (TLR4) in regulating bovine mammary epithelial transcriptional responses to S. aureus SCV challenge remains poorly understood. Using CRISPR-Cas9-generated TLR4-knockout (TLR4-KO) MAC-T cells combined with RNA sequencing, global transcriptional responses of wild-type (WT) and TLR4-KO MAC-T cells infected with S. aureus SCV Heba3231 and its isogenic parental strain (PS) were compared. The WT cells mounted highly divergent S. aureus strain-specific responses, with only 0.5% overlap in differentially expressed genes between PS and SCV conditions. The PS infection induced apoptotic and HIF-1 signalling pathways, whereas SCV infection promoted lipid metabolic reprogramming, accompanied by suppression of epithelial barrier integrity genes. TLR4 disruption dramatically amplified transcriptional dysregulation, with a 192-fold increase for the PS (1,921 DEGs) and a 6.6-fold increase for SCV (2,279 DEGs) relative to WT infected controls. This revealed a large core set of TLR4-regulated genes with approximately 57% shared across S. aureus strains that govern innate immunity, structural homeostasis, and apoptotic coordination. WFDC2, ITGB3, SH3BGRL, and HKDC1 emerged as novel TLR4-dependent candidate genes. Collectively, these findings identify TLR4 as a key determinant of strain-specific transcriptional discrimination and epithelial homeostasis during S. aureus infection, with particular relevance to SCV-mediated persistence in bovine mastitis.
2026-06-08 | GSE334132 | 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:Staphylococcus aureus small colony variants (SCVs) are a persistence-adapted phenotype associated with chronic and recurrent bovine mastitis. The interleukin-10 receptor ⍺ (IL10RA) is a key regulator of anti-inflammatory signalling in the mammary gland, yet its role in governing transcriptional responses to intracellular staphylococcal challenge remains unknown. Using CRISPR/Cas9-generated IL10RA knockout (KO) MAC-T bovine mammary epithelial cells (MECs) and RNA sequencing, we compared transcriptional responses to infection with S. aureus SCV Heba3231 and its isogenic parental strain (PS). The wild-type (WT) MAC-T cells mounted fundamentally divergent responses to the PS (8 DEGs) and the SCV (461 DEGs), with no transcriptional overlap, indicating strain-specific engagement of distinct molecular programmes. SCV infection of WT cells up-regulated lipid and sterol biosynthetic pathways, and suppressed genes associated with epithelial barrier integrity, including S100A8, S100A9, TGM3 and KRTDAP. IL10RA disruption dramatically amplified transcriptional dysregulation. The IL10RA-KO cells infected with the PS yielded 619 DEGs (77.4-fold increase over WT-PS), while IL10RA-KO cells infected with SCV yielded 1,297 DEGs (2.8-fold increase over WT-SCV). A moderate core of IL10RA-regulated genes (~32–36%) was shared across infection conditions. IL10RA loss derepressed pro-inflammatory cytokine pathways (TNF, IL-17), enhanced pro-apoptotic programmes during SCV infection, and suppressed phagosomal maturation and lipid metabolic gene programmes. Novel candidate genes, including CD79B, WFDC2, AMN and LY6E, were identified as potential biomarkers of IL10RA-dependent mammary immune signalling. These findings establish IL10RA as a broad transcriptional homeostasis regulator in bovine mammary epithelial cells during intracellular staphylococcal infection.
2026-06-08 | GSE334081 | 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 (∆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