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New mutation in parE in a pneumococcal in vitro mutant resistant to fluoroquinolones
C Janoir1, E Varon, M D Kitzis
1L.R.M.A., Université Paris VI, 75270 Paris Cedex 06, France.
Abstract:
For an in vitro mutant of Streptococcus pneumoniae selected on moxifloxacin four- to eightfold-increased MICs of new fluoroquinolones, only a twofold-increased MIC of ciprofloxacin, and a twofold-decreased MIC of novobiocin were observed. This phenotype was conferred by two mutations: Ser81Phe in GyrA and a novel undescribed His103Tyr mutation in ParE, outside the quinolone resistance-determining region, in the putative ATP-binding site of topoisomerase IV.
Insights
New fluoroquinolone resistance in Streptococcus pneumoniae involves two key mutations. A novel mutation in ParE, alongside a GyrA alteration, explains the observed resistance patterns and reduced novobiocin susceptibility.
Area of Science:
- Microbiology
- Molecular Biology
- Antimicrobial Resistance
Background:
- Fluoroquinolones are critical antibiotics for treating Streptococcus pneumoniae infections.
- Understanding resistance mechanisms is essential for developing new therapeutic strategies.
- Streptococcus pneumoniae exhibits increasing resistance to existing antimicrobial agents.
Purpose of the Study:
- To investigate the molecular basis of fluoroquinolone resistance in an in vitro mutant of Streptococcus pneumoniae.
- To identify specific mutations conferring altered susceptibility to fluoroquinolones and novobiocin.
Main Methods:
- Selection of an in vitro mutant of Streptococcus pneumoniae on moxifloxacin.
- Determination of minimum inhibitory concentrations (MICs) for various fluoroquinolones and novobiocin.
- Genetic analysis to identify mutations in key resistance-associated genes (GyrA and ParE).
Main Results:
- The mutant displayed four- to eightfold-increased MICs for new fluoroquinolones and a twofold-increased MIC for ciprofloxacin.
- A twofold-decreased MIC of novobiocin was observed in the resistant mutant.
- Two mutations were identified: Ser81Phe in GyrA and a novel His103Tyr mutation in ParE.
Conclusions:
- The identified Ser81Phe (GyrA) and His103Tyr (ParE) mutations are responsible for the observed fluoroquinolone resistance phenotype.
- The novel ParE mutation, located outside the quinolone resistance-determining region in the ATP-binding site of topoisomerase IV, contributes significantly to resistance.
- These findings enhance our understanding of fluoroquinolone resistance mechanisms in Streptococcus pneumoniae and highlight potential targets for future drug development.