Transcriptional profiling of a Staphylococcus aureus ΔyqeK mutant under acetic acid stress
Ontology highlight
ABSTRACT:
ORGANISM(S): Staphylococcus aureus
PROVIDER: GSE319508 | GEO | 2026/05/15
REPOSITORIES: GEO
Similar Datasets
Project description:Staphylococcus aureus YqeK is an Ap4A hydrolase that degrades the alarmone adenosine tetraphosphate (Ap4A). Ap4A is produced by aminoacyl-tRNA synthetases as a byproduct of aminoacylation during stress. In other bacteria, excessive Ap4A accumulation has been linked to reduced oxidative and heat stress tolerance, increased antibiotic susceptibility, and reduced biofilm formation. However, the role of Ap4A metabolism in S. aureus has not been characterized. Here, we show that deletion of yqeK results in Ap4A accumulation in S. aureus, which is exacerbated under stress conditions. The ΔyqeK mutant exhibits growth defects relative to wild-type during acetic acid and nitric oxide stress. Transcriptional profiling under nitric oxide stress revealed dysregulation of nucleotide biosynthesis, hallmarks of translational stress, and reduced expression of key virulence genes, including the agr quorum sensing system. Altogether, our data suggest that YqeK is critical for S. aureus stress adaptation and that Ap4A accumulation links nucleotide homeostasis and translational stress to virulence regulation.
2026-05-15 | GSE319509 | GEO
Project description:While a plethora of small regulatory RNAs (sRNAs) have been identified in the human pathogen Staphylococcus aureus, the physiological function of most of them remains unknown. We report the characterization of SprY, a sRNA from S. aureus expressed from a pathogenicity island. RNAIII, a major regulator of S. aureus virulence, was discovered as a potential SprY target by an MS2-affinity purification assay. In silico interaction studies suggest a RNA-RNA pairing between the SprY 5’end and the 13rd stem-loop of RNAIII. Overproduction of SprY leads to a 1.5-fold reduction of RNAIII amount. By affecting the rnaIII expression, SprY affects the amount of RNAIII known targets. Indeed, SprY downregulates hla mRNA translation, but also upregulates other secreted factors such as Ecb and Rot. Furthermore, SprY decreases the hemolytic activity and virulence of S. aureus. Our results lead to propose that SprY is involved in S. aureus virulence through a post-transcriptional regulation of RNAIII.
2021-02-10 | GSE166499 | GEO
Project description:The Staphylococcus aureus accessory gene regulator (agr) is a prototype quorum-sensing system in Gram-positive bacteria and a paradigmatic example of gene regulation by a small regulatory RNA, RNAIII. Using genome-wide transcriptional profiling in the community-associated methicillin-resistant (CA-MRSA) strain MW2, we demonstrate here that in contrast to the current model of target gene regulation by agr, a large subset of agr-regulated genes is controlled independently of RNAIII. This group comprised predominantly metabolism genes, whereas virulence factors were mostly controlled by RNAIII. Remarkably, the phenol-soluble modulin (PSM) leukocidin genes were the only virulence determinants under RNAIII-independent control, emphasizing their exceptional role in S. aureus physiology and pathogenesis. Of note, PSM promoters bound the AgrA response regulator protein, previously believed to interact exclusively with agr promoters, explaining the exceptionally strict control of PSMs by agr. Our results suggest that virulence factor control is a secondary acquisition of the agr regulon, which evolved by development of RNAIII around the mRNA of the PSM d-toxin, exemplifying how gene control via a small regulatory RNA may be linked to a pre-established regulatory circuit. In addition to elucidating agr control in CA-MRSA, which revealed features potentially crucial for CA-MRSA pathogenesis, our study establishes a novel two-level model of cell-density dependent gene regulation in S. aureus and gives important insight into the connection of metabolism and virulence control in this leading opportunistic pathogen. Keywords: Wild type control vs mutant Wild type in triplicate is compared to mutant in triplicate totalling 27 samples
2010-05-14 | E-GEOD-10165 | biostudies-arrayexpress
Project description:The Staphylococcus aureus accessory gene regulator (agr) is a prototype quorum-sensing system in Gram-positive bacteria and a paradigmatic example of gene regulation by a small regulatory RNA, RNAIII. Using genome-wide transcriptional profiling in the community-associated methicillin-resistant (CA-MRSA) strain MW2, we demonstrate here that in contrast to the current model of target gene regulation by agr, a large subset of agr-regulated genes is controlled independently of RNAIII. This group comprised predominantly metabolism genes, whereas virulence factors were mostly controlled by RNAIII. Remarkably, the phenol-soluble modulin (PSM) leukocidin genes were the only virulence determinants under RNAIII-independent control, emphasizing their exceptional role in S. aureus physiology and pathogenesis. Of note, PSM promoters bound the AgrA response regulator protein, previously believed to interact exclusively with agr promoters, explaining the exceptionally strict control of PSMs by agr. Our results suggest that virulence factor control is a secondary acquisition of the agr regulon, which evolved by development of RNAIII around the mRNA of the PSM d-toxin, exemplifying how gene control via a small regulatory RNA may be linked to a pre-established regulatory circuit. In addition to elucidating agr control in CA-MRSA, which revealed features potentially crucial for CA-MRSA pathogenesis, our study establishes a novel two-level model of cell-density dependent gene regulation in S. aureus and gives important insight into the connection of metabolism and virulence control in this leading opportunistic pathogen. Keywords: Wild type control vs mutant
2009-01-05 | GSE10165 | 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:Staphylococcus aureus is an important food poisoning bacterium. In food preservation, acidification is a well-known method. Permeant weak organic acids, like lactic and acetic acids, are known to be more effective against bacteria than inorganic strong acids (e.g., HCl). Growth experiments and metabolic and transcriptional analyses were used to determine the responses of a food pathogenic S. aureus strain exposed to lactic acid, acetic acid, and HCl at pH 4.5. Lactic and acetic acid stress induced a slower transcriptional response and large variations in growth patterns compared with the responses induced by HCl. In cultures acidified with lactic acid, the pH of the medium gradually increased to 7.5 during growth, while no such increase was observed for bacteria exposed to acetic acid or HCl. Staphylococcus aureus increased the pH in the medium mainly through accumulation of ammonium and the removal of acid groups, resulting in increased production of diacetyl (2,3-butanedione) and pyrazines. The results showed flexible and versatile responses of S. aureus to different types of acid stress. As measured by growth inhibition, permeant organic acid stress introduced severe stress compared with the stress caused by HCl. Cells exposed to lactic acid showed specific mechanisms of action in addition to sharing many of the mechanisms induced by HCl stress. Data is also available from http://bugs.sgul.ac.uk/E-BUGS-87
2011-04-15 | E-BUGS-87 | biostudies-arrayexpress
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:The agr quorum-sensing system clearly links Staphylococcus aureus metabolism to virulence, but little is known about how agr alters metabolism to affect cell survival during severe stress. Recently, we reported that agr activity increases survival of bacteria during treatment with lethal concentrations of H2O2, a crucial host defense against S. aureus. Here we report that protection by agr extends to growth resumption during the exit from stationary phase. The data indicate that the agr functionality of a cell’s ancestor affects stress-resiliency after resuming growth. Protection against killing by H2O2 depended on the agr effector molecule RNAIII and Rot, a transcription factor targeted by RNAIII. Expression data revealed that Δagr strains shift to fermentation, suggesting that agr promotes aerobic respiration. Epistasis between mutation of agr and sortase, which anchors surface proteins to the cell wall, suggested that reduced killing by H2O2 of wild-type agr strains acts through down-regulation of surface proteins that perturb respiration. Respiration generates reactive oxygen species (ROS), moderate amounts of which can protect from subsequent challenge by lethal concentrations, explaining agr-mediated protection against subsequent lethal H2O2 doses. Increased survival of wild-type agr cells in response to H2O2 required sodA, which dismutates O2- to H2O2, suggesting that sodA helps induce the low, protective levels of ROS triggered by agr. Additionally, detrimental effects of the Δagr mutation require ahpC, which functions to decrease the intracellular level of H2O2. Deletion of ahpC or sortase attenuated neutrophil-mediated killing of Δagr strains, demonstrating the importance of priming in anticipation of impending immune attack.
2023-06-20 | GSE206916 | GEO
Project description:The agr quorum-sensing system clearly links Staphylococcus aureus metabolism to virulence, but little is known about how agr alters metabolism to affect cell survival during severe stress. Recently, we reported that agr activity increases survival of bacteria during treatment with lethal concentrations of H2O2, a crucial host defense against S. aureus. Here we report that protection by agr extends to growth resumption during the exit from stationary phase. The data indicate that the agr functionality of a cell’s ancestor affects stress-resiliency after resuming growth. Protection against killing by H2O2 depended on the agr effector molecule RNAIII and Rot, a transcription factor targeted by RNAIII. Expression data revealed that Δagr strains shift to fermentation, suggesting that agr promotes aerobic respiration. Epistasis between mutation of agr and sortase, which anchors surface proteins to the cell wall, suggested that reduced killing by H2O2 of wild-type agr strains acts through down-regulation of surface proteins that perturb respiration. Respiration generates reactive oxygen species (ROS), moderate amounts of which can protect from subsequent challenge by lethal concentrations, explaining agr-mediated protection against subsequent lethal H2O2 doses. Increased survival of wild-type agr cells in response to H2O2 required sodA, which dismutates O2- to H2O2, suggesting that sodA helps induce the low, protective levels of ROS triggered by agr. Additionally, detrimental effects of the Δagr mutation require ahpC, which functions to decrease the intracellular level of H2O2. Deletion of ahpC or sortase attenuated neutrophil-mediated killing of Δagr strains, demonstrating the importance of priming in anticipation of impending immune attack.
2023-06-20 | GSE206889 | GEO
Project description:Staphylococcus lugdunensis is a coagulase-negative Staphylococcus that emerges as an important opportunistic pathogen. However, little is known about the regulation underlying the transition from commensal to virulent state. Based on knowledge of S. aureus virulence, we suspected that the agr quorum sensing system may be an important determinant for the pathogenicity of S. lugdunensis. We investigated the functions of the transcriptional regulator AgrA using the agrA deletion mutant. AgrA played a role in cell pigmentation: ∆argA mutant colonies were white while the parental strains were slightly yellow. Compared to the wild-type strain, the ∆argA mutant was affected in its ability to form biofilm and was less able to survive in mice macrophages. Moreover, the growth of ∆agrA was significantly reduced by the addition of 10 % NaCl or 0.4 mM H2O2 and its survival after 2 h in presence of 1 mM H2O2 was more than 10-fold reduced. To explore the mechanisms involved beyond these phenotypes, the ∆agrA proteome and transcriptome were characterized by mass spectrometry and RNA-Seq. We found that AgrA controlled several virulence factors as well as stress-response factors, which are well correlated with the reduced resistance of the ∆agrA mutant to osmotic and oxidative stresses. These results were not the consequence of the deregulation of RNAIII of the agr system, since no phenotype or alteration of the proteomic profile has been observed for the ∆RNAIII mutant. Altogether, our results highlighted that the AgrA regulator of S. lugdunensis played a key role in its ability to become pathogenic.
2022-02-22 | PXD028347 | Pride