Journal article
Quinolone Resistance Due to Reduced Target Enzyme Expression
Journal of bacteriology, Vol.185(23), pp.6883-6892
12/2003
DOI: 10.1128/JB.185.23.6883-6892.2003
PMCID: PMC262703
PMID: 14617652
Abstract
We report for the first time low-level quinolone resistance mediated by decreased expression of topoisomerase IV in
Staphylococcus aureus
. A single-step mutant of wild-type
S. aureus
strain ISP794, P18 selected by using twice the MIC of premafloxacin, had four- and four- to eightfold greater MICs of premafloxacin and ciprofloxacin, respectively, than the wild type. Sequencing of
parEC
and
gyrBA
with their promoter regions revealed a point mutation (G→A) 13 bp upstream of the start codon of
parE
. Genetic linkage studies showed that there was a high level of correlation between the mutation and the resistance phenotype, and allelic exchange confirmed the contribution of the mutation to resistance. Decreased expression of ParE and decreased steady-state levels of
parEC
transcripts in P18 and in resistant allelic exchange mutants were observed. The steady-state levels of
gyrBA
and
topB
transcripts were increased in P18 but not in two resistant allelic exchange mutants, and sequencing upstream of either gene did not reveal a difference between ISP794 and P18. The steady-state levels of
topA
transcripts were similar in the various strains. Growth competition experiments performed at 30, 37, and 41°C with a susceptible allelic exchange strain and a resistant allelic exchange strain suggested that loss of fitness was associated with reduced levels of ParE at 41°C. However, P18 had a growth advantage over ISP794 at all temperatures, suggesting that a compensatory mechanism was associated with the increased levels of
gyrBA
and
topB
transcripts. Thus, reduced levels of ParE appear to be compatible with cell survival, although there may be a fitness cost during rapid cell multiplication, which might be overcome by compensatory mechanisms without reversion of the resistance phenotype.
Details
- Title: Subtitle
- Quinolone Resistance Due to Reduced Target Enzyme Expression
- Creators
- Dilek Ince - Division of Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MassachusettsDavid C Hooper - Division of Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
- Resource Type
- Journal article
- Publication Details
- Journal of bacteriology, Vol.185(23), pp.6883-6892
- DOI
- 10.1128/JB.185.23.6883-6892.2003
- PMID
- 14617652
- PMCID
- PMC262703
- NLM abbreviation
- J Bacteriol
- ISSN
- 0021-9193
- eISSN
- 1098-5530
- Publisher
- American Society for Microbiology
- Language
- English
- Date published
- 12/2003
- Academic Unit
- Infectious Diseases; Internal Medicine
- Record Identifier
- 9984094713102771
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