Examining the role of mupirocin-induced nutritional stress in the S. aureus stringent stress response
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PROVIDER: PRJNA433003 | ENA |
REPOSITORIES: ENA
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Project description:The stringent response is a conserved stress response employed by various bacteria to respond to and cope with conditions of amino acid starvation, carbon-source, fatty acid, oxygen/iron limitation, heat shock, antimicrobial challenge, and/or other environmental stressors. In S. aureus, the stringent response is mediated in part by enzyme RSH (relA spoT homologue) which synthesizes two nucleotide-based molecules, guanosine tetraphosphate (ppGpp) and pentaphosphate (pppGpp), collectively known as (p) ppGpp. This response is known to result in a number of diverse physiological and metabolic changes which we further characterized in the present study. Specifically, the global transcriptome of the RSH synthase mutant (rshsyn) was compared to the WT parent S. aureus strain (NCTC 8325) by RNA-Seq analysis under both normal and nutrient-limited media conditions. In order to mimic nutrient limitation, bacteria were treated with mupirocin, an antibiotic and isoleucine analogue known to lead to isoleucine starvation. In the WT strain, in response to mupirocin-induced isoleucine starvation, genes encoding protein synthesis machinery were suppressed while genes encoding amino acid biosynthetic machinery were upregulated. This response likely employed to compensate for amino acid deprivation, was not induced in the stringent response mutant. Furthermore, under starvation conditions, biofilm-related genes (i.e. icaA, icaC, fnbA, clfB, emp) were more upregulated in the WT than the stringent response mutant. Moreover, the effect of mupirocin caused a stronger upregulation of several proteases (i.e. sspA, sspP, sppB, aur), lipases (lip, geh) and phenol soluble modulin toxins in the WT as compared to the mutant. Overall, these results suggest that under starvation conditions, RSH plays an important role in helping the cell respond to nutritional stress as well as regulates the expression of numerous colonization and virulence factors.
2019-02-02 | GSE110170 | GEO
Project description:Transcriptome analysis of D39 rel+Spn and delta-relSpn strains treated with mupirocin revealed relSpn-independent (translation stress), relSpn-dependent (stringent response), and delta-relSpn-dependent changes suggesting that relSpn and (p)ppGpp amount play wide-ranging homeostatic roles in pneumococcal physiology, besides adjusting macromolecular synthesis and transport in response to nutrient availability. Wildtype and rel deletion mutant (Delta rel) bacteria were grown statically in BHI broth at 37C in an atmosphere of 5% CO2. Cultures were divided in two upon reaching a density of OD620 ~0.1, and lithium mupirocin was added to one culture (t=0) to a final concentration of 100 ng per mL. Treated and untreated cultures were harvested after 20 min further incubation and RNA was extracted by a hot lysis-acid phenol protocol. We performed the following comparisons: Wildtype + mupirocin versus Wildtype untreated (reference); Delta rel + mupirocin versus Delta rel untreated (reference); Delta rel untreated versus Wildtype untreated (reference); Delta rel + mupirocin versus Wildtype + mupirocin (reference). For each comparison, microarray data were obtained from three independent biological replicates and included one dye swap.
2010-05-15 | E-GEOD-14750 | biostudies-arrayexpress
Project description:Transcriptome analysis of D39 rel+Spn and delta-relSpn strains treated with mupirocin revealed relSpn-independent (translation stress), relSpn-dependent (stringent response), and delta-relSpn-dependent changes suggesting that relSpn and (p)ppGpp amount play wide-ranging homeostatic roles in pneumococcal physiology, besides adjusting macromolecular synthesis and transport in response to nutrient availability.
2010-01-11 | GSE14750 | GEO
Project description:In the present study we analyzed the response of S. aureus to mupirocin, the drug of choice for nasal decolonization of S. aureus. Mupirocin selectively inhibits the bacterial isoleucyl-tRNA synthetase (IleRSs) leading to the accumulation of uncharged isoleucyl-tRNA and hence (p)ppGpp. The latter is a signal for the induction of the stringent response, an important global transcriptional and translational control mechanism that allows bacteria to adapt to nutritional deprivation. To identify proteins with an altered synthesis pattern in response to mupirocin treatment we used the highly sensitive 2-dimensional gel electrophoresis technique in combination with mass spectrometry. Obtained results were complemented by DNA-microarray, Northern blot and metabolome analysis. Whereas expression of genes involved in nucleotide biosynthesis, DNA metabolism, energy metabolism and translation was significantly down-regulated, expression of the isoleucyl-tRNA synthetase, the branched chain amino acids pathway, genes with functions in oxidative stress resistance (ahpC, katA), putative roles in stress protection (SACOL1759, SACOL2131, SACOL0815) and transport processes was increased. Of particular interest were the differences in the transcription of genes encoding virulence associated regulators (i.e. arlRS, saeRS, sarA, sarR, sarS) as well as genes directly involved in the virulence of S. aureus (i.e. fnbA, epiE, epiG, seb). In the present study we analyzed the response of S. aureus to mupirocin, the drug of choice for nasal decolonization of S. aureus. Mupirocin selectively inhibits the bacterial isoleucyl-tRNA synthetase (IleRSs) leading to the accumulation of uncharged isoleucyl-tRNA and hence (p)ppGpp. The latter is a signal for the induction of the stringent response, an important global transcriptional and translational control mechanism that allows bacteria to adapt to nutritional deprivation. In total four independent hybridization experiments with each representing a biological replicate including a control and a treated sample were carried out. To account for the dye bias two of the four replicates were dye swapped.
2012-01-23 | E-GEOD-30743 | biostudies-arrayexpress
Project description:Stringent-controlled stress adaption of Pseudomonas aeruginosa
| PRJNA576893 | ENA
Project description:In the present study we analyzed the response of S. aureus to mupirocin, the drug of choice for nasal decolonization of S. aureus. Mupirocin selectively inhibits the bacterial isoleucyl-tRNA synthetase (IleRSs) leading to the accumulation of uncharged isoleucyl-tRNA and hence (p)ppGpp. The latter is a signal for the induction of the stringent response, an important global transcriptional and translational control mechanism that allows bacteria to adapt to nutritional deprivation. To identify proteins with an altered synthesis pattern in response to mupirocin treatment we used the highly sensitive 2-dimensional gel electrophoresis technique in combination with mass spectrometry. Obtained results were complemented by DNA-microarray, Northern blot and metabolome analysis. Whereas expression of genes involved in nucleotide biosynthesis, DNA metabolism, energy metabolism and translation was significantly down-regulated, expression of the isoleucyl-tRNA synthetase, the branched chain amino acids pathway, genes with functions in oxidative stress resistance (ahpC, katA), putative roles in stress protection (SACOL1759, SACOL2131, SACOL0815) and transport processes was increased. Of particular interest were the differences in the transcription of genes encoding virulence associated regulators (i.e. arlRS, saeRS, sarA, sarR, sarS) as well as genes directly involved in the virulence of S. aureus (i.e. fnbA, epiE, epiG, seb). In the present study we analyzed the response of S. aureus to mupirocin, the drug of choice for nasal decolonization of S. aureus. Mupirocin selectively inhibits the bacterial isoleucyl-tRNA synthetase (IleRSs) leading to the accumulation of uncharged isoleucyl-tRNA and hence (p)ppGpp. The latter is a signal for the induction of the stringent response, an important global transcriptional and translational control mechanism that allows bacteria to adapt to nutritional deprivation.
2012-01-23 | GSE30743 | GEO
Project description:Surfing motility is a complex adaptation that is different from swarming motility and requires the stringent stress response in Pseudomonas aeruginosa LESB58 Cystic fibrosis (CF) is a genetic disease that affects mucin-producing body organs such as the lungs. Characteristic of CF is the production of thick and sticky mucus that can lead to progressive airway obstruction. The glycoprotein mucin is the major macromolecular component of mucus. Recently, we identified that the presence of mucin induced a rapid surface adaptation termed surfing motility in motile bacteria. P. aeruginosa, the main colonizing pathogen in CF employs several stress coping mechanisms to survive the highly viscous environment of the CF lung. Here, RNA-Seq was used to study the stringent stress response in the hypervirulent CF isolate LESB58 (Liverpool Epidemic Strain) via transcriptional profiling. As the stringent response is regulated by relA and spoT, we created a double knockout of these genes in LESB58 to study the impact of these stress regulators on surfing motility using RNA-Seq.
2020-03-11 | GSE138716 | GEO
Project description:We show that NtrC couples the Ntr stress response and stringent response in N starved E. coli, which appears to be a conserved adaptive strategy employed by many bacteria to manage conditions of nutritional adversity. N starved Escherichia coli initiate the nitrogen regulation (Ntr) stress response as an adaptive mechanism to scavenge for alternative N sources. The Ntr stress response requires the global transcriptional regulator nitrogen regulatory protein C (NtrC). We discovered that the transcription of relA, the key gene responsible for the synthesis of the major effector nucleotide alamorne of the bacterial stringent response, guanosine pentaphosphate (ppGpp), is positively regulated by NtrC in N starved E. coli. we addressed Ntr stress response-ppGpp alarmone links and mapped the genome-wide binding targets of NtrC in E. coli during N starvation using chromatin immunoprecipitation (ChIP) followed by high-throughput sequencing (ChIP-seq) to gain insight into the NtrC-dependent gene networks. To identify candidate genome regions that are preferentially associated with NtrC, we introduced an in-frame fusion encoding three repeats of the FLAG epitope to the 3-prime end of glnG in E. coli strain NCM3722, a prototrophic E. coli K-12 strain.
2014-05-01 | E-MTAB-2211 | biostudies-arrayexpress
Project description:This study is an analysis of changes in gene expression during stringent response in Vibrio cholerae. V. cholerae cells in mid-log were treated with serine hydroxamate and gene expression was compared to untreated cells. Keywords: Stress response, stringent response
2006-12-28 | GSE6616 | GEO
Project description:The stringent response was defined in Lactococcus lactis through transcript profiling after the addition of a chemical inductor, the norvaline. Gene expression was measured in the exponential growth phase (reference sample) and at 1.6 h after norvaline addition. Four hundred and sixty one differentially expressed genes were identified and constituted the stringent response regulon. Keywords: stress response, time course
2009-04-28 | GSE10254 | GEO