Author:
Truong-Bolduc Que Chi,Bolduc Gilles R.,Okumura Ryo,Celino Brian,Bevis Jennifer,Liao Chun-Hsing,Hooper David C.
Abstract
ABSTRACTStaphylococcus aureusis an important pathogen that adapts and survives in low-pH environments. One component of this adaptation involves the regulation of genes encoding bacterial transporters that could affect response to antibiotics under these conditions. We previously demonstrated that the transcriptional regulator MgrA in its phosphorylated form (MgrA-P) represses the expression ofnorB, encoding the NorB multidrug resistance efflux pump. In this study, we focused on changes in the expression ofmgrAat the transcriptional and posttranslational levels, following a shift from pH 7.0 to pH 4.5. We then correlated those changes with modifications in transcript levels ofnorBand to resistance to moxifloxacin, a substrate of NorB. At pH 4.5,S. aureusMgrA increased 2-fold and MgrA-P decreased 4-fold, associated with an 8-fold increase innorBtranscripts and a 6-fold reduction in bacterial killing by moxifloxacin, and the phenomenon was dependent on intactmgrA. Taken together, these new data showed that phosphoregulation of MgrA at low pH reverses its repression ofnorBexpression, conferring resistance to moxifloxacin.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
38 articles.
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