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High-Throughput Screening for Inhibitors of Wall Teichoic Acid Biosynthesis in Staphylococcus aureus

Omar M El-Halfawy1,2,3, Eric D Brown4,5

  • 1Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada.

Methods in Molecular Biology (Clifton, N.J.)
|March 14, 2019
PubMed

Insights

New screening methods identify novel inhibitors of wall teichoic acid (WTA) biosynthesis in Staphylococcus aureus. These WTA inhibitors offer a promising strategy against antibiotic-resistant bacteria like MRSA.

Area of Science:

  • Microbiology
  • Drug Discovery
  • Infectious Diseases

Background:

  • The rise of antibiotic resistance, particularly Methicillin-resistant Staphylococcus aureus (MRSA), necessitates novel therapeutic strategies.
  • Wall teichoic acids (WTA) are crucial for S. aureus virulence and resistance to beta-lactam antibiotics.
  • Targeting WTA biosynthesis presents a promising avenue for developing new antibacterial agents.

Purpose of the Study:

  • To develop and implement a high-throughput screening platform for identifying inhibitors of WTA biosynthesis in S. aureus.
  • To validate the identified compounds through dose-response assays.

Main Methods:

  • A whole-cell screening platform was designed utilizing the unique dispensability patterns of genes involved in WTA biosynthesis.
  • Primary bioactive hits were subjected to follow-up dose-response assays to determine their inhibitory concentrations.

Main Results:

  • The screening platform successfully identified compounds that inhibit WTA biosynthesis.
  • Follow-up assays confirmed the efficacy of selected WTA inhibitors.

Conclusions:

  • The developed screening platform is effective for discovering novel inhibitors of WTA biosynthesis.
  • WTA inhibitors represent a promising class of compounds for combating drug-resistant staphylococcal infections.
  • This approach offers a new mechanism to fight against MRSA infections.
Keywords:
Antagonism screenAntibacterialAntibioticSmall-molecule librarySmall-molecule screeningStaphylococcus aureusWall teichoic acid

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