The iron starvation response of the Staphylococcus aureus hemB small colony variant (SCV)
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ABSTRACT:
ORGANISM(S): Staphylococcus aureus subsp. aureus USA300
PROVIDER: GSE184082 | GEO | 2022/09/06
REPOSITORIES: GEO
Similar Datasets
Project description:Compilation fo whole genome gene expression changes in Staphylococcus aureus USA300 LAC cultures grown in the presence of vehicle or the anti-gout drug benzbromarone. The drug was intially screened as effective against the agr quorum sensing system in Staphylococcus aureus AH1677. A microarray study using total RNA harvested from three cultures of Staphylococcus aureus USA300 LAC plus vehicle control and three cultures of Staphylococcus aureus USA300 LAC plus 12 uM benzbromarone.
2014-03-19 | E-GEOD-55980 | biostudies-arrayexpress
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 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: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:Compilation fo whole genome gene expression changes in Staphylococcus aureus USA300 LAC cultures grown in the presence of vehicle or the anti-gout drug benzbromarone. The drug was intially screened as effective against the agr quorum sensing system in Staphylococcus aureus AH1677.
2014-03-19 | GSE55980 | GEO
Project description:Staphylococcus aureus is a leading cause of bloodstream infections worldwide. In the United States, many of these infections are caused by a strain known as USA300. Although progress has been made, our understanding of the S. aureus molecules that promote bacteremia and survival in human blood is incomplete. To that end, we analyzed the USA300 transcriptome during culture in human blood, human serum, and trypticase soy broth (TSB), a standard laboratory culture media. Notably, genes encoding several cytolytic toxins were up-regulated in human blood over time, and hlgA, hlgB, and hlgC (encoding gamma-hemolysin subunits HlgA, HlgB, and HlgC) were among the most highly up-regulated genes at all time points. Culture supernatants derived from a USA300 isogenic hlgABC-deletion strain (LAC?hlgABC) had significantly reduced capacity to form pores in human neutrophils and ultimately cause neutrophil lysis. Compared with the wild-type USA300 strain (LAC), LAC?hlgABC had modestly reduced ability to cause mortality in a mouse bacteremia model. On the other hand, wild-type and LAC?hlgABC strains caused virtually identical disease in a mouse skin infection model, and bacterial survival and neutrophil lysis after phagocytosis in vitro was similar between these strains. Comparison of the cytolytic capacity of culture supernatants from wild-type and isogenic deletion strains lacking hlgABC, lukS/F-PV (encoding PVL), and/or lukDE revealed significant functional redundancy among two-component leukotoxins in vitro. These findings may explain in part the apparent limited contribution of any single two-component leukotoxin to USA300 immune evasion and virulence. S. aureus strain USA300 transcriptome during culture in human blood, human serum, and trypticase soy broth (TSB): time course.
2011-08-25 | E-GEOD-25454 | biostudies-arrayexpress
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:The iron starvation response of the Staphylococcus aureus hemB small colony variant (SCV)
| PRJNA763127 | ENA
Project description:S. aureus has the propensity to survive a range of NaCl challenge conditions We used commercially available Affymetrix S. aureus GeneChips (part number 900514) to compare the gene expression properties of wild type cells during growth at no or high (2M) NaCl. S. aureus strain USA300-lac cells were grown to late exponential phase growth in the absence or presence of 2M NaCl, total bacterial RNA was isolated and subjected to GeneChip hybridization and analysis. We sought to determine the regulatory effects of high NaCl.
2013-07-01 | E-GEOD-46383 | biostudies-arrayexpress