A defect in cell wall recycling confers antibiotic resistance and sensitivity in Staphylococcus aureus.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA872000 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR21159790_1.fastq.gz | Fastqsanger.gz | |||
| SRR21159790_2.fastq.gz | Fastqsanger.gz | |||
| SRR21159791_1.fastq.gz | Fastqsanger.gz | |||
| SRR21159791_2.fastq.gz | Fastqsanger.gz | |||
| SRR21159792_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 18 |
Similar Datasets
Project description:WalKR is a two-component system that is essential for viability in Gram-positive bacteria that regulates the all-important autolysins. Here we show a T101M mutation in walR confers a defect in autolysis, a thickened cell wall and decreased sensitivity to antibiotics that target the lipid II cycle, a phenotype that is reminiscent of the clinical resistance form known as vancomycin intermediate-resistant Staphylococcus aureus. Importantly, this is accompanied by dramatic sensitization to tunicamycin. We demonstrate that this phenotype is due to partial collapse of a pathway consisting of autolysins, AtlA and Sle1, a transmembrane sugar permease, MurP, and GlcNAc recycling enzymes, MupG and MurQ. We suggest that this causes a shortage of substrate for MraY causing it to be hypersensitive to competitive inhibition by tunicamycin. This constitutes a new molecular model for antibiotic sensitivity in S. aureus and a promising new route for antibiotic discovery.
2022-08-25 | GSE211745 | GEO
Project description:WalKR is a two-component system that is essential for viability in Gram-positive bacteria that regulates the all-important autolysins in cell wall homeostasis. Further investigation of this essential system is important for identifying ways to address antibiotic resistance. Here, we show that a T101M mutation in walR confers a defect in autolysis, a thickened cell wall, and decreased susceptibility to antibiotics that target lipid II cycle, a phenotype that is reminiscent of the clinical resistance form known as vancomycin intermediate-resistant Staphylococcus aureus. Importantly, this is accompanied by dramatic sensitization to tunicamycin. We demonstrate that this phenotype is due to partial collapse of a pathway consisting of autolysins, AtlA and Sle1, a transmembrane sugar permease, MurP, and GlcNAc recycling enzymes, MupG and MurQ. We suggest that this causes a shortage of substrate for the peptidoglycan biosynthesis enzyme MraY, causing it to be hypersensitive to competitive inhibition by tunicamycin. In conclusion, our results constitute a new molecular model for antibiotic sensitivity in S. aureus and a promising new route for antibiotic discovery.
| S-EPMC9547203 | biostudies-literature
Project description:A noncoding variant confers pancreatic differentiation defect
| PRJNA1051034 | ENA
Project description:Hcr1/eIF3j is a sub-stoichiometric subunit of eukaryotic initiation factor 3 (eIF3) that can dissociate the post-termination 40S ribosomal subunit from mRNA in vitro. We examined this ribosome recycling role in vivo by ribosome profiling and reporter assays and found that loss of Hcr1 led to reinitiation of translation in 3’UTRs, consistent with a defect in recycling. However, the defect appeared to be in recycling of the 60S subunit, rather than the 40S subunit, because reinitiation did not require an AUG codon and was suppressed by overexpression of the 60S dissociation factor Rli1/ABCE1. Consistent with a 60S recycling role, overexpression of Hcr1 could not compensate for loss of 40S recycling factors Tma64/eIF2D and Tma20/MCT-1. Intriguingly, loss of Hcr1 triggered higher expression of RLI1 via an apparent feedback loop. These findings suggest Hcr1/eIF3j is recruited to ribosomes at stop codons and may coordinate the transition to a new round of translation.
2019-05-23 | GSE124204 | GEO
Project description:RNA Polymerase II transcriptional recycling is an underappreciated mechanism for which the required factors and contributions to overall gene expression levels are poorly understood. We describe an in vitro methodology facilitating unbiased identification of novel RNA Pol II transcriptional recycling factors and quantitative measurement of transcriptional output from recycled transcriptional components. Proof-of-principle experiments identified PAF1 complex components among recycling factors and detected defective transcriptional output from RNA Pol II recycling following PAF1 depletion. Dynamic ChIP-seq confirmed in vivo PAF1 complex cycling through gene bodies with RNA Pol II and recycling back to the transcription start sites, while PAF1 silencing triggered defective RNA Pol II recycling. Prostate tumors exhibited enhanced transcriptional recycling, which was attenuated by antibody-based PAF1 depletion. These findings identify RNA Pol II recycling as a potential target in cancer and demonstrate the assay’s applicability to characterize RNA Pol II recycling in cells and tissues from other disease states.
2021-10-07 | GSE133655 | GEO
Project description:Parental histone recycling is essential for the restoration of chromatin-based epigenetic information during chromatin replication; however, the specific mechanisms underlying the local recycling of parental histones remain poorly understood. Here, we reveal an unexpected role of the Spt16-N domain in histone chaperone FACT during parental histone recycling and transfer in budding yeast. We found that depletion of Spt16 or mutations in the Spt16 middle domain leads to defects in both parental histone recycling and new histone deposition, affecting both the leading and lagging strands of DNA replication forks, highlighting the essential role of the FACT complex in both parental histone recycling and new histone deposition. Surprisingly, Spt16-N deletion results in an apparent defect in parental histone recycling, with a more pronounced defect on the lagging strand than the corresponding leading strand. Mechanistically, the Spt16-N domain acts as a protective barrier, shielding FACT-bound histone H3-H4 and facilitating its interaction with Mcm2, which ensures efficient local parental histone recycling. Collectively, the Spt16-N domain provides a protein–protein interaction module allowing FACT to act as a shuttle chaperone, cooperate with multiple replisome components, which act as co-chaperones, to form a complex involving the shuttle chaperone, histones, and co-chaperones, during parental histone recycling and transfer.
2024-01-26 | PXD043392 | Pride
Project description:Yeast strains lacking orthologs of mammalian eIF2D (Tma64), and either MCT-1 (Tma20) or DENR (Tma22) are broadly impaired for 40S recycling; however, it was unknown whether this defect leads to reduced 43S PIC levels with an impact on translation of particular mRNAs. To test this, we by combined ribosome footprint profiling with RNA-seq analysis of mRNA abundance.
2021-03-31 | GSE166987 | GEO
Project description:GWAS provided many β cell function-associated single nucleotide polymorphisms (SNPs) without clearly pathogenic mechanism. Stepwise differentiation of pancreatic β cells provide the promise to study developmental genetic disorders. Here, we focused on SNP rs6048205 (A/G) located in downstream noncoding region of FOXA2, which was annotated with fast glucose and β cell function risk. We introduced the mutation into human pluripotent stem cells, directed pancreatic differentiation revealed that risk G mutation reduce the percentage of PDX1+NKX6-1+ progenitor cells at pancreatic progenitor 2 stage (PP2), and then defect the function of β cells in-vitro. Mechanistically, risk allele G variant could alter the upstream factor RXRA binding to ectopically promote the expression of FOXA2, which is an important transcription factor in pancreatic development.
2024-10-20 | GSE249854 | GEO
Project description:Chitin is an important fungal cell wall component that is cross-linked to β-glucan for structural integrity. Acquisition of chitin to glucan cross-links has previously been shown to be performed by transglycosylation enzymes in S. cerevisiae, called Congo Red hypersensitive (Crh) enzymes. Here, we characterized the impact of deleting all seven gene members of the crh gene family (crhA-G) in Aspergillus niger on cell wall integrity, cell wall composition and genome-wide gene expression. In this study, we show that the seven-fold knockout strain shows slightly compact plate growth, but no increased sensitivity to cell wall perturbing compounds. Additionally, we found that the cell wall composition of this knockout strain was virtually identical to that of the wild type. In congruence with these data, genome-wide expression analysis revealed very limited changes in gene expression and no signs of activation of the cell wall integrity response pathway. However, deleting the entire crh gene family in cell wall mutants that are deficient in either galactofuranose (ΔugmA) or α-glucan (ΔagsE and ΔagsA, ΔagsE), resulted in a synthetic growth defect and an increased sensitivity towards Congo Red compared the parental strains. Altogether, these results indicate that loss of the crh gene family in A. niger does not trigger the cell wall integrity response in itself, but does play an important role in ensuring cell wall integrity in mutant strains with reduced galactofuranose or α-glucan.
2019-12-21 | GSE142461 | GEO