title: Implication of the NorB efflux pump in the adaptation of Staphylococcus aureus to growth at acid pH and in resistance to moxifloxacin.
abstract: Staphylococcus aureus is 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 of norB, encoding the NorB multidrug resistance efflux pump. In this study, we focused on changes in the expression of mgrA at 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 of norB and to resistance to moxifloxacin, a substrate of NorB. At pH 4.5, S. aureus MgrA increased 2-fold and MgrA-P decreased 4-fold, associated with an 8-fold increase in norB transcripts and a 6-fold reduction in bacterial killing by moxifloxacin, and the phenomenon was dependent on intact mgrA. Taken together, these new data showed that phosphoregulation of MgrA at low pH reverses its repression of norB expression, conferring resistance to moxifloxacin.
authors.affiliation: Division of Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114-2696, USA.
authors.forename: Que Chi
authors.initials: QC
authors.lastname: Truong-Bolduc
authors.forename: Gilles R
authors.initials: GR
authors.lastname: Bolduc
authors.forename: Ryo
authors.initials: R
authors.lastname: Okumura
authors.forename: Brian
authors.initials: B
authors.lastname: Celino
authors.forename: Jennifer
authors.initials: J
authors.lastname: Bevis
authors.forename: Chun-Hsing
authors.initials: CH
authors.lastname: Liao
authors.forename: David C
authors.initials: DC
authors.lastname: Hooper
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001372:Aza Compounds / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D024881:Drug Resistance, Bacterial / Q000235:genetics; D005434:Flow Cytometry; D024841:Fluoroquinolones; D015964:Gene Expression Regulation, Bacterial; D006863:Hydrogen-Ion Concentration; D008826:Microbial Sensitivity Tests; D000077266:Moxifloxacin; D011804:Quinolines / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D001372:Aza Compounds; D001426:Bacterial Proteins; D024841:Fluoroquinolones; D011804:Quinolines; D000077266:Moxifloxacin