Expression of the Multidrug Resistance Transporter NorA from
            <i>Staphylococcus aureus</i>
            Is Modified by a Two-Component Regulatory System

Fournier, Bénédicte; Aras, Rahul; Hooper, David C.

doi:10.1128/jb.182.3.664-671.2000

Cited by 110 publications

(83 citation statements)

References 42 publications

(27 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although disruption of the gene for the ArlS transmembrane sensor resulted in upregulation of NorA expression and also altered the growth phase regulation of this transporter, it is not known if ArlS phosphorylates the 18-kDa protein directly or, alternatively, acts indirectly, e.g., via ArlR altering the transcription of a gene involved in the production of a ligand for the 18-kDa protein (35). The latter scenario could be related to the observation that S. aureus secretes a compound into the external medium that has the effect of lowering norA expression from the late logarithmic growth phase onwards (35).…”

Section: Drug Transporter Expression In Other Pathogens and Antibiotimentioning

confidence: 99%

“…Although the regulation of norA expression is poorly understood, an unidentified 18-kDa protein has been demonstrated to bind to multiple sites in the DNA sequences upstream of the Ϫ35 region of the norA promoter (35). The binding of this 18-kDa protein is modified by ArlS, which appears to function as the transmembrane sensor of a two-component regulatory system, ArlR-ArlS.…”

Section: Drug Transporter Expression In Other Pathogens and Antibiotimentioning

confidence: 99%

“…The latter scenario could be related to the observation that S. aureus secretes a compound into the external medium that has the effect of lowering norA expression from the late logarithmic growth phase onwards (35). Although ArlR-ArlS also has a role in the regulation of virulence determinants in S. aureus (36), the expression of norA does not appear to be linked to that of known virulence determinants, suggesting that ArlR-ArlS modulates NorA expression in response to other physiological functions (35).…”

Section: Drug Transporter Expression In Other Pathogens and Antibiotimentioning

confidence: 99%

See 2 more Smart Citations

Regulation of Bacterial Drug Export Systems

Grkovic

Brown

Skurray

2002

Microbiol Mol Biol Rev

354

339

View full text Add to dashboard Cite

The active transport of toxic compounds by membrane-bound efflux proteins is becoming an increasingly frequent mechanism by which cells exhibit resistance to therapeutic drugs. This review examines the regulation of bacterial drug efflux systems, which occurs primarily at the level of transcription. Investigations into these regulatory networks have yielded a substantial volume of information that has either not been forthcoming from or complements that obtained by analysis of the transport proteins themselves. Several local regulatory proteins, including the activator BmrR from Bacillus subtilis and the repressors QacR from Staphylococcus aureus and TetR and EmrR from Escherichia coli, have been shown to mediate increases in the expression of drug efflux genes by directly sensing the presence of the toxic substrates exported by their cognate pump. This ability to bind transporter substrates has permitted detailed structural information to be gathered on protein-antimicrobial agent-ligand interactions. In addition, bacterial multidrug efflux determinants are frequently controlled at a global level and may belong to stress response regulons such as E. coli mar, expression of which is controlled by the MarA and MarR proteins. However, many regulatory systems are ill-adapted for detecting the presence of toxic pump substrates and instead are likely to respond to alternative signals related to unidentified physiological roles of the transporter. Hence, in a number of important pathogens, regulatory mutations that result in drug transporter overexpression and concomitant elevated antimicrobial resistance are often observed

show abstract

Section: Drug Transporter Expression In Other Pathogens and Antibiotimentioning

confidence: 99%

Section: Drug Transporter Expression In Other Pathogens and Antibiotimentioning

confidence: 99%

Section: Drug Transporter Expression In Other Pathogens and Antibiotimentioning

confidence: 99%

See 1 more Smart Citation

Regulation of Bacterial Drug Export Systems

Grkovic

Brown

Skurray

2002

Microbiol Mol Biol Rev

354

339

View full text Add to dashboard Cite

show abstract

“…Such systems consist of a histidine kinase that senses drugs extracellularly and phosphorylates the response regulator, which modulates the expression of MDR pumps. Some examples are AlrSR (36), which regulates the expression of NorA of S. aureus, and EvgAS (101), which modulates the expression of the RND transporter YhiUV of E. coli.…”

Section: Regulation Of Mdr Abc Transportersmentioning

confidence: 99%

Distribution and Physiology of ABC-Type Transporters Contributing to Multidrug Resistance in Bacteria

Lubelski

Konings

Driessen

2007

Microbiol Mol Biol Rev

268

188

View full text Add to dashboard Cite

SUMMARY Membrane proteins responsible for the active efflux of structurally and functionally unrelated drugs were first characterized in higher eukaryotes. To date, a vast number of transporters contributing to multidrug resistance (MDR transporters) have been reported for a large variety of organisms. Predictions about the functions of genes in the growing number of sequenced genomes indicate that MDR transporters are ubiquitous in nature. The majority of described MDR transporters in bacteria use ion motive force, while only a few systems have been shown to rely on ATP hydrolysis. However, recent reports on MDR proteins from gram-positive organisms, as well as genome analysis, indicate that the role of ABC-type MDR transporters in bacterial drug resistance might be underestimated. Detailed structural and mechanistic analyses of these proteins can help to understand their molecular mode of action and may eventually lead to the development of new strategies to counteract their actions, thereby increasing the effectiveness of drug-based therapies. This review focuses on recent advances in the analysis of ABC-type MDR transporters in bacteria.

show abstract

“…This pump protects the cell from quinolones such as norfloxacin as well as from ethidium bromide and cetrimide (15,16). We have previously shown that the regulation of norA expression is complex and includes a two-component regulatory system, ArlSArlR, and specific binding of an 18-kDa protein to the norA promoter (5). Many details of the regulation of norA expression, however, remain unclear.…”

mentioning

confidence: 99%

A Mutation in the 5′ Untranslated Region Increases Stability of norA mRNA, Encoding a Multidrug Resistance Transporter of Staphylococcus aureus

et al. 2001

Self Cite

View full text Add to dashboard Cite

NorA, a multidrug efflux pump in Staphylococcus aureus, protects the cell from multiple drugs, including quinolones. The flqB mutation (T3G) in the 5 untranslated region upstream of norA causes norA overexpression of 4.9-fold in cis, as measured in norA::blaZ fusions. The transcriptional initiation site of norA was unchanged in mutant and wild-type strains, but the half-life of norA mRNA was increased 4.8-fold in the flqB mutant compared to the wild-type strain. Computer-generated folding of the first 68 nucleotides of the norA transcript predicts an additional stem-loop and changes in a putative RNase III cleavage site in the flqB mutant.

show abstract

Expression of the Multidrug Resistance Transporter NorA from Staphylococcus aureus Is Modified by a Two-Component Regulatory System

Cited by 110 publications

References 42 publications

Regulation of Bacterial Drug Export Systems

Regulation of Bacterial Drug Export Systems

Distribution and Physiology of ABC-Type Transporters Contributing to Multidrug Resistance in Bacteria

A Mutation in the 5′ Untranslated Region Increases Stability of norA mRNA, Encoding a Multidrug Resistance Transporter of Staphylococcus aureus

Contact Info

Product

Resources

About