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NsaRS is a cell-envelope-stress-sensing two-component system of Staphylococcus aureus
- Source :
- Microbiology (Reading, England). 157(Pt 8)
- Publication Year :
- 2011
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 14652080
- Volume :
- 157
- Issue :
- Pt 8
- Database :
- OpenAIRE
- Journal :
- Microbiology (Reading, England)
- Accession number :
- edsair.doi.dedup.....a73a23608d453f4ac9b8d4209659b73a