Transcriptional regulation of drug efflux genes by EvgAS, a two-component system in Escherichia coli.
A constitutively active mutant of histidine kinase sensor EvgS was found to confer multi-drug resistance (MDR) to an acrA-deficient Escherichia coli, indicating the relationship between the two-component system EvgAS and the expression of the MDR system. The observed MDR also depended on an outer-membrane channel, TolC. Microarray and S1 mapping assays indicated that, in the presence of this constitutive mutant EvgS, the level of transcription increased for some MDR genes, including the drug efflux genes emrKY, yhiUV, acrAB, mdfA and tolC. Transcription in vitro of emrK increased by the addition of phosphorylated EvgA. Transcription activation of tolC by the activated EvgS was, however, dependent on both EvgAS and PhoPQ (Mg(2+)-responsive two-component system), in agreement with the presence of the binding site (PhoP box) for the regulator PhoP in the tolC promoter region. Transcription in vitro of yhiUV also appears to require an as-yet-unidentified additional transcriptional factor besides EvgA. Taken together we propose that the expression of the MDR system is under a complex regulatory network, including the phosphorylated EvgA serving as the master regulator.
Eguchi
Yoko
Y
Department of Bioscience and Biotechnology, Graduate School of Agriculture of Kinki University, 3327-204, Nakamachi, Nara 631-8505, Japan.
Oshima
Taku
T
Research and Education Center for Genetic Information, Nara Institute of Science and Technology, Ikoma 630-0101, Japan.
Mori
Hirotada
H
Research and Education Center for Genetic Information, Nara Institute of Science and Technology, Ikoma 630-0101, Japan.
Aono
Rikizo
R
Department of Bioengineering, Faculty of Bioscience and Biotechnology, Tokyo Institute of Technology, Nagatsuta 4259, Midori-ku, Yokohama 226-0027, Japan.
Yamamoto
Kaneyoshi
K
Department of Bioscience and Biotechnology, Graduate School of Agriculture of Kinki University, 3327-204, Nakamachi, Nara 631-8505, Japan.
Ishihama
Akira
A
Division of Molecular Biology, Nippon Institute for Biological Science, Ome, Tokyo 190-0024, Japan.
Utsumi
Ryutaro
R
Department of Bioscience and Biotechnology, Graduate School of Agriculture of Kinki University, 3327-204, Nakamachi, Nara 631-8505, Japan.
D001425:Bacterial Outer Membrane Proteins / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D004926:Escherichia coli / Q000235:genetics*; D029968:Escherichia coli Proteins / Q000502:physiology*; D015964:Gene Expression Regulation, Bacterial; D019450:Genes, MDR; D026901:Membrane Transport Proteins / Q000235:genetics; D016366:Open Reading Frames; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic
D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; C065601:BvgA protein, Bacteria; D029968:Escherichia coli Proteins; C489314:EvgA protein, E coli; C118438:Mdfa protein, E coli; D026901:Membrane Transport Proteins; D014157:Transcription Factors; C080662:bvgS protein, Bordetella pertussis; C073126:tolC protein, E coli