title: FarR regulates the farAB-encoded efflux pump of Neisseria gonorrhoeae via an MtrR regulatory mechanism.
abstract: The farAB operon of Neisseria gonorrhoeae encodes an efflux pump which mediates gonococcal resistance to antibacterial fatty acids. It was previously observed that expression of the farAB operon was positively regulated by MtrR, which is a repressor of the mtrCDE-encoded efflux pump system (E.-H. Lee and W. M. Shafer, Mol. Microbiol. 33:839-845, 1999). This regulation was believed to be indirect since MtrR did not bind to the farAB promoter. In this study, computer analysis of the gonococcal genome sequence database, lacZ reporter fusions, and gel mobility shift assays were used to elucidate the regulatory mechanism by which expression of the farAB operon is modulated by MtrR in gonococci. We identified a regulatory protein belonging to the MarR family of transcriptional repressors and found that it negatively controls expression of farAB by directly binding to the farAB promoter. We designated this regulator FarR to signify its role in regulating the farAB operon. We found that MtrR binds to the farR promoter, thereby repressing farR expression. Hence, MtrR regulates farAB in a positive fashion by modulating farR expression. This MtrR regulatory cascade seems to play an important role in adjusting levels of the FarAB and MtrCDE efflux pumps to prevent their excess expression in gonococci.
authors.affiliation: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
authors.forename: E-H
authors.initials: EH
authors.lastname: Lee
authors.forename: C
authors.initials: C
authors.lastname: Rouquette-Loughlin
authors.forename: J P
authors.initials: JP
authors.lastname: Folster
authors.forename: W M
authors.initials: WM
authors.lastname: Shafer
mesh_terms: D026921:Amino Acid Transport Systems, Neutral / Q000378:metabolism*; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D005287:Ferredoxin-NADP Reductase; D015964:Gene Expression Regulation, Bacterial; D007763:Lac Operon; D009344:Neisseria gonorrhoeae / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000502:physiology; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D026921:Amino Acid Transport Systems, Neutral; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C091146:mngR protein, E coli; C087450:mtrR protein, Neisseria gonorrhoeae; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase