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Journal of Bacteriology, February 2000, p. 664-671, Vol. 182, No. 3
0021-9193/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Expression of the Multidrug Resistance Transporter
NorA from Staphylococcus aureus Is Modified by a
Two-Component Regulatory System
Bénédicte
Fournier,1,2
Rahul
Aras,1 and
David C.
Hooper1,*
Infectious Disease Division and Medical
Services, Massachusetts General Hospital, Harvard Medical School,
Boston, Massachusetts 02114-2696,1 and
Unité de Biochimie Microbienne, Institut Pasteur, 25, rue du Docteur Roux, 75724 Paris Cedex 15, France2
Received 14 July 1999/Accepted 11 November 1999
To dissect genetically the regulation of NorA, a multidrug
transporter of Staphylococcus aureus, we analyzed the
differential expression of the norA promoter using a
transcriptional fusion with a
-lactamase reporter gene. Expression
studies with an arlS mutant revealed that the
norA promoter is ArlS dependent. The arlR-arlS
locus was shown to code for a two-component regulatory system. The
protein ArlR has strong similarity to response regulators, and ArlS has
strong similarity to protein histidine kinases. We have also analyzed
the 350-bp region upstream of the Shine-Dalgarno sequence of
norA by gel mobility shift experiments. It was shown that
only the 115-bp region upstream of the promoter was necessary for
multiple binding of an 18-kDa protein. From transcriptional fusions, we
have localized four different putative boxes of 6 bp, which appear to
play a role in the binding of the 18-kDa protein and in the
up-regulation of norA expression in the presence of the
arlS mutation. Furthermore, the gel mobility shift of the 18-kDa protein was modified in the presence of the arlS
mutation, and the arlS mutation altered the growth-phase
regulation of NorA. These results indicate that expression of
norA is modified by a two-component regulatory system.
*
Corresponding author. Mailing address: Infectious
Disease Division, Massachusetts General Hospital, 55 Fruit St., Boston, MA 02114-2696. Phone: (617) 726-3812. Fax: (617) 726-7416. E-mail: dhooper{at}partners.org.
Journal of Bacteriology, February 2000, p. 664-671, Vol. 182, No. 3
0021-9193/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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