NsaRS is a cell-envelope-stress-sensing two-component system of Staphylococcus aureus
| Autor: | Mohamed O. Elasri, Halie K. Miller, Anna Oszmiana, Frances E. Rivera, Joanna Koziel, David S. Barber, Lindsey N. Shaw, James T. Riordan, Jessica E. Davenport, Vijayaraj Nagarajan, Stacey L. Kolar, Jan Potempa |
|---|---|
| Přispěvatelé: | Kolar, Stacey L, Nagarajan, Vijayaraj, Oszmiana, Anna, Rivera, Frances E, Miller, Halie K, Davenport, Jessica E, Riordan, James T, Potempa, Jan, Barber, David S, Koziel, Joanna, Elasri, Mohamed O, Shaw, Lindsey N |
| Rok vydání: | 2011 |
| Předmět: |
Staphylococcus aureus
Histidine Kinase Mutant antimicrobial agents Biology Microbiology Cell membrane anaerobic gene-expression bacillus subtilis Bacterial Proteins Genes Reporter Stress Physiological medicine Transcriptional regulation Escherichia coli methicillin resistant Regulation of gene expression Gene Expression Profiling Histidine kinase Cell Membrane transduction system Membrane Proteins Gene Expression Regulation Bacterial beta-Galactosidase Two-component regulatory system Anti-Bacterial Agents Artificial Gene Fusion medicine.anatomical_structure Biochemistry Cell and Molecular Biology of Microbes biofilm formation Cell envelope Protein Kinases Intracellular Signal Transduction Transcription Factors |
| Zdroj: | Microbiology (Reading, England). 157(Pt 8) |
| ISSN: | 1465-2080 |
| Popis: | Staphylococcus aureus possesses 16 two-component systems (TCSs), two of which (GraRS and NsaRS) belong to the intramembrane-sensing histidine kinase (IM-HK) family, which is conserved within the firmicutes. NsaRS has recently been documented as being important for nisin resistance in S. aureus. In this study, we present a characterization of NsaRS and reveal that, as with other IM-HK TCSs, it responds to disruptions in the cell envelope. Analysis using a lacZ reporter–gene fusion demonstrated that nsaRS expression is upregulated by a variety of cell-envelope-damaging antibiotics, including phosphomycin, ampicillin, nisin, gramicidin, carbonyl cyanide m-chlorophenylhydrazone and penicillin G. Additionally, we reveal that NsaRS regulates a downstream transporter NsaAB during nisin-induced stress. NsaS mutants also display a 200-fold decreased ability to develop resistance to the cell-wall-targeting antibiotic bacitracin. Microarray analysis reveals that the transcription of 245 genes is altered in an nsaS mutant, with the vast majority being downregulated. Included within this list are genes involved in transport, drug resistance, cell envelope synthesis, transcriptional regulation, amino acid metabolism and virulence. Using inductively coupled plasma-MS we observed a decrease in intracellular divalent metal ions in an nsaS mutant when grown under low abundance conditions. Characterization of cells using electron microscopy reveals that nsaS mutants have alterations in cell envelope structure. Finally, a variety of virulence-related phenotypes are impaired in nsaS mutants, including biofilm formation, resistance to killing by human macrophages and survival in whole human blood. Thus, NsaRS is important in sensing cell damage in S. aureus and functions to reprogram gene expression to modify cell envelope architecture, facilitating adaptation and survival. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|