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Quinolone resistance mutations in the GrlB protein of Staphylococcus aureus

M Tanaka1, Y Onodera, Y Uchida

  • 1New Product Research Laboratories I, Daiichi Pharmaceutical Co. Ltd., Edogawa-ku, Tokyo 134-8630, Japan. tanakpmj@daiichipharm.co.jp

Antimicrobial Agents and Chemotherapy
|October 31, 1998
PubMed

Insights

Altered GrlB proteins in Staphylococcus aureus may lead to quinolone resistance. Specifically, an Asp-432 to Asn change in GrlB suggests a mechanism for bacterial resistance to antibiotics like levofloxacin.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Drug Resistance

Background:

  • Staphylococcus aureus is a significant human pathogen.
  • Quinolones are a class of antibiotics used to treat bacterial infections.
  • GrlB is a subunit of DNA gyrase and topoisomerase IV, essential enzymes for bacterial DNA replication.

Purpose of the Study:

  • To investigate the role of specific alterations in the GrlB protein of Staphylococcus aureus in conferring resistance to quinolone antibiotics.
  • To determine the impact of Asp-432-->Asn and Asn-470-->Asp mutations in GrlB on levofloxacin susceptibility.

Main Methods:

  • Purification of altered GrlB proteins as maltose-binding protein fusion proteins.
  • Determination of the 50% inhibitory concentrations (IC50) of levofloxacin against purified topoisomerase IV containing the altered GrlB proteins.

Main Results:

  • The GrlB protein with an Asp-432-->Asn alteration showed a 50% inhibitory concentration of 14 microg/ml for levofloxacin.
  • The GrlB protein with an Asn-470-->Asp alteration exhibited a lower 50% inhibitory concentration of 3.4 microg/ml for levofloxacin.

Conclusions:

  • The alteration of Asp to Asn at position 432 in the GrlB protein of Staphylococcus aureus is suggested to be a key factor in developing quinolone resistance.
  • Understanding these mutations can aid in developing strategies to combat antibiotic resistance.

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