학술논문

Effect of Promoter Region Mutations and mgrAOverexpression on Transcription of norA, Which Encodes a Staphylococcus aureusMultidrug Efflux Transporter
Document Type
Article
Source
Antimicrobial Agents and Chemotherapy; January 2005, Vol. 49 Issue: 1 p161-169, 9p
Subject
Language
ISSN
00664804; 10986596
Abstract
ABSTRACTNorA is a Staphylococcus aureusmultidrug transporter that confers resistance to structurally distinct compounds. The MgrA global regulatory protein is reported to augment norAexpression when mgrAis overexpressed from an undefined plasmid-based promoter. Further details about norAregulatory mechanisms are scant. A chromosomal norA::lacZtranscriptional fusion was constructed in different S. aureusstrains, and allele replacement was used to define the relevance of promoter region sequences to norAexpression. The effect of mgrAoverexpression in wild-type and mutant backgrounds was also determined. Contrary to existing data, overexpression of mgrArepressed norAtranscription in all parent and selected norApromoter mutant strains in a dose-dependent fashion. Disruption of a near-perfect inverted repeat or other putative regulatory protein binding sites did not affect norAtranscription, but the repressive effect of mgrAoverexpression was blunted in these mutants. This result, and the conservation of all of these motifs in S. aureus, suggests that their presence is required for the full effect of MgrA, or other regulatory proteins, on norAexpression. Mutations at the +5 nucleotide of norAmRNA (flqBmutations) had a major impact; all resulted in markedly increased norAexpression that was significantly reversed by mgrAoverexpression. The flqBposition of norAmRNA is part of a conserved imperfect inverted repeat; it is feasible that this motif could be a binding site for a norAregulatory protein.