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Identification of an efflux pump gene, pmrA, associated with fluoroquinolone resistance in Streptococcus pneumoniae
M J Gill1, N P Brenwald, R Wise
1Division of Immunity and Infection, University of Birmingham Medical School, Birmingham B15 2TT, United Kingdom. m.j.gill@bham.ac.uk
Abstract:
An open reading frame (ORF) homologous to norA was insertionally inactivated with cat in a fluoroquinolone-resistant pneumococcus with an efflux phenotype; this inactivation caused reversion to drug sensitivity. The ORF product has 24% amino acid sequence identity each to NorA and Bmr, which suggests that it is a major facilitator system pump of the 12-transmembrane-segment class.
Insights
Inactivating a norA-like gene in fluoroquinolone-resistant pneumococcus restored drug sensitivity. This suggests the gene encodes a major facilitator system pump.
Area of Science:
- Microbiology
- Molecular Biology
- Drug Resistance
Background:
- Fluoroquinolone resistance in Streptococcus pneumoniae is a growing public health concern.
- Efflux pumps play a significant role in multidrug resistance in bacteria.
- The norA gene in Staphylococcus aureus is a well-characterized fluoroquinolone efflux pump.
Purpose of the Study:
- To investigate the role of a norA-homologous open reading frame (ORF) in fluoroquinolone resistance in Streptococcus pneumoniae.
- To determine if inactivation of this ORF could restore susceptibility to fluoroquinolones.
Main Methods:
- Insertionally inactivated the norA-homologous ORF using the cat gene in a fluoroquinolone-resistant pneumococcal strain.
- Assessed the resulting strain for fluoroquinolone susceptibility and efflux phenotype.
- Performed sequence analysis to determine the putative function and class of the ORF product.
Main Results:
- Inactivation of the norA-homologous ORF resulted in a complete reversion to fluoroquinolone sensitivity.
- The identified ORF product shares 24% amino acid identity with NorA and Bmr, known multidrug efflux pumps.
- The sequence homology suggests the ORF encodes a 12-transmembrane-segment major facilitator superfamily (MFS) transporter.
Conclusions:
- The studied norA-homologous ORF is crucial for the fluoroquinolone resistance and efflux phenotype in this pneumococcal isolate.
- This ORF likely encodes a novel MFS efflux pump contributing to antimicrobial resistance in Streptococcus pneumoniae.
- Targeting such efflux pumps could be a viable strategy to combat fluoroquinolone resistance.