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Staphylococcus aureus mutants selected by BMS-284756.

L F Discotto1, L E Lawrence, K L Denbleyker

  • 1Bristol-Myers Squibb Pharmaceutical Research Institute, Infectious Diseases, Department of Microbiology, Wallingford, Connecticut 06492, USA. Linda.Discotto@bms.com

Antimicrobial Agents and Chemotherapy
|October 16, 2001
PubMed
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Researchers studied Staphylococcus aureus mutants to understand how BMS-284756, a des-fluoroquinolone antibiotic, works. The findings indicate that DNA gyrase is the main target of this novel quinolone in S. aureus.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Pharmacology

Background:

  • Staphylococcus aureus is a significant human pathogen.
  • Quinolone antibiotics are crucial for treating bacterial infections.
  • Understanding antibiotic mechanisms is vital for combating resistance.

Purpose of the Study:

  • To investigate the in vitro activity of BMS-284756 against Staphylococcus aureus.
  • To identify the primary molecular target of BMS-284756 in S. aureus.

Main Methods:

  • Selection of in vitro mutants of Staphylococcus aureus ISP794 using BMS-284756.
  • Sequencing of quinolone resistance-determining regions in gyrA, gyrB, grlA, and grlB genes.

Main Results:

Related Experiment Videos

  • Step mutants resistant to BMS-284756 were successfully generated.
  • Sequence analysis revealed alterations in target genes associated with quinolone resistance.

    • Conclusions:

    • The data strongly suggest that DNA gyrase is the primary molecular target of BMS-284756 in Staphylococcus aureus.
    • BMS-284756 represents a promising novel quinolone with a defined mechanism of action.