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Cloning and sequencing of Staphylococcus aureus murC, a gene essential for cell wall biosynthesis
1Channing Laboratory and the Infectious Disease Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Abstract:
Staphylococcus aureus is a major human pathogen that is increasingly resistant to clinically useful antimicrobial agents. While screening for S. aureus genes expressed during mammalian infection, we isolated murC. This gene encodes UDP-N-acetylmuramoyl-L-alanine synthetase, an enzyme essential for cell wall biosynthesis in a number of bacteria. S. aureus MurC has a predicted mass 49,182 Da and complements the temperature-sensitive murC mutation of E. coli ST222. Sequence data on the DNA flanking staphylococcal murC suggests that the local gene organization there parallels that found in B. subtilis, but differs from that found in gram-negative bacterial pathogens. MurC proteins represent promising targets for broad spectrum antimicrobial drug development.
Insights
Researchers identified the murC gene in Staphylococcus aureus, which is crucial for bacterial cell wall synthesis. This discovery highlights MurC proteins as potential targets for developing new antimicrobial drugs against resistant bacteria.
Area of Science:
- Microbiology
- Molecular Biology
- Drug Discovery
Background:
- Staphylococcus aureus is a significant human pathogen known for its increasing antimicrobial resistance.
- Bacterial cell wall biosynthesis is a critical process for bacterial survival and a validated target for antibiotics.
Purpose of the Study:
- To identify and characterize genes involved in Staphylococcus aureus virulence and survival during infection.
- To evaluate the potential of bacterial enzymes in cell wall synthesis as targets for novel antimicrobial agents.
Main Methods:
- Screening of Staphylococcus aureus genes expressed during mammalian infection.
- Isolation and functional characterization of the murC gene.
- Complementation studies using Escherichia coli temperature-sensitive murC mutants.
- Sequence analysis of the DNA flanking the staphylococcal murC gene.
Main Results:
- The murC gene, encoding UDP-N-acetylmuramoyl-L-alanine synthetase, was isolated from Staphylococcus aureus.
- Staphylococcus aureus MurC demonstrated functional complementation of an Escherichia coli murC mutation, confirming its essential role in cell wall biosynthesis.
- Comparative sequence analysis revealed differences in gene organization compared to gram-negative pathogens, suggesting potential species-specific drug development strategies.
Conclusions:
- The staphylococcal murC gene product is essential for bacterial cell wall synthesis.
- MurC proteins represent a promising target class for the development of broad-spectrum antimicrobial drugs, particularly against resistant strains of Staphylococcus aureus.