Objectives: The skin commensal and opportunistic pathogen Staphylococcus epidermidis is one of the leading causes of nosocomial and biofilm-associated infections, which urgently requires discovery of new antibiotics. We decided to find new leads that target the S. epidermidis tryptophanyl-tRNA synthetase (SeWRS), which is essential for translation.
Methods: We applied an approach combining structure-based discovery in silico with biochemical and biological experiments in vitro to screen SeWRS inhibitors.
Results: Three compounds have an inhibitory effect on enzymatic activities of SeWRS, of which two show low inhibition of the human tryptophanyl-tRNA synthetase. Binding of these compounds to bacterially expressed SeWRS was demonstrated by surface plasmon resonance technology. These three compounds can also obviously inhibit growth of S. epidermidis in vitro and displayed low cytotoxicity to mammalian cells.
Conclusions: These compounds are good leads to develop new antibiotics.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1093/jac/dkm229 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Assembly of the Human Multi-tRNA Synthetase Complex Through Leucine Zipper Motifs.
J Mol Biol
December 2024
School of Life Science and Biotechnology, KNU Creative BioResearch Group, Kyungpook National University, Daegu 41566, Republic of Korea. Electronic address:
Aminoacyl-tRNA synthetases (ARSs) are responsible for the ligation of amino acids to their cognate tRNAs. In human, nine ARSs form a multi-tRNA synthetase complex (MSC) with three ARS-interacting multifunctional proteins (AIMPs). Among the components of MSC, arginyl-tRNA synthetase 1 (RARS1) and two AIMPs (AIMP1 and AIMP2) have leucine zipper (LZ) motifs, which they utilize for their assembly in an MSC.
View Article and Find Full Text PDFWars1 downregulation in hepatocytes induces mitochondrial stress and disrupts metabolic homeostasis.
Metabolism
January 2025
Laboratory of Metabolic Signaling, Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland. Electronic address:
Several laboratories, including ours, have employed the Slc25a47 mouse model to investigate the role of SLC25A47, a hepatocyte-specific mitochondrial carrier, in regulating hepatic metabolism and systemic physiology. In this study, we reveal that the hepatic and systemic phenotypes observed following recombination of the Slc25a47-Wars1 locus in hepatocytes are primarily driven by the unexpected downregulation of Wars1, the cytosolic tryptophan aminoacyl-tRNA synthetase located adjacent to Slc25a47. While the downregulation of Wars1 predictably affects cytosolic translation, we also observed a significant impairment in mitochondrial protein synthesis within hepatocytes.
View Article and Find Full Text PDFCoexisting bacterial aminoacyl-tRNA synthetase paralogs exhibit distinct phylogenetic backgrounds and functional compatibility with Escherichia coli.
IUBMB Life
December 2024
Department of Molecular Biology and Biophysics, UConn Health, Farmington, Connecticut, USA.
Aminoacyl-tRNA synthetases (aaRSs) are universally essential enzymes that synthesize aminoacyl-tRNA substrates for protein synthesis. Although most organisms require a single aaRS gene for each proteinogenic amino acid to translate their genetic information, numerous species encode multiple gene copies of an aaRS. Growing evidence indicates that organisms acquire extra aaRS genes to sustain or adapt to their unique lifestyle.
View Article and Find Full Text PDFTryptophanyl tRNA synthetase is an alternative synovial biomarker for diagnosis of septic arthritis in knee joint.
Knee Surg Relat Res
September 2024
Department of Orthopaedic Surgery, Gil Medical Center, Gachon University College of Medicine, Incheon, 21565, Republic of Korea.
Article Synopsis
- The study aims to assess tryptophanyl tRNA synthetase (WRS) as a diagnostic tool for septic arthritis of the knee, comparing its effectiveness to other biomarkers in distinguishing it from other forms of arthritis.* -
- A total of 62 patients with various arthritis types were analyzed, revealing that those with septic arthritis had significantly higher levels of WRS and other inflammatory markers, with WRS showing a high specificity (87.5%) and sensitivity (83.3%).* -
- The findings suggest WRS in synovial fluid could serve as a reliable biomarker for diagnosing septic arthritis, marking the need for further testing in separate patient groups.*
Evaluation of Neuroprotective Effect of Gut Microbe in Parkinson's Disease: An In Silico and In Vivo Approach.
Neuromolecular Med
August 2024
Birla Institute of Scientific Research, Jaipur, Rajasthan, 302020, India.
Parkinson's disease is a progressive neurodegenerative disorder marked by the death of dopaminergic neurons in the substantia nigra region of the brain. Aggregation of alpha-synuclein (α-synuclein) is a contributing factor to Parkinson's disease pathogenesis. The objective of this study is to investigate the neuroprotective effects of gut microbes on α-synuclein aggregation using both in silico and in vivo approaches.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!