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Journal of Bacteriology, May 2009, p. 3273-3281, Vol. 191, No. 10
0021-9193/09/$08.00+0     doi:10.1128/JB.00151-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Identification and Characterization of a Novel Multidrug Resistance Operon, mdtRP (yusOP), of Bacillus subtilis{triangledown}

Ji-Yun Kim,1,2 Takashi Inaoka,1 Kazutaka Hirooka,3 Hiroshi Matsuoka,3 Makiko Murata,4 Reiko Ohki,4 Yoshikazu Adachi,2 Yasutaro Fujita,3 and Kozo Ochi1*

National Food Research Institute, Tsukuba, Ibaraki 305-8642, Japan,1 Laboratory of Animal Health, School of Agriculture, Ibaraki University, Ami, Ibaraki 300-0393, Japan,2 Department of Biotechnology, Faculty of Life Science and Technology, Fukuyama University, Fukuyama, Hiroshima, 729-0292, Japan,3 Department of Molecular Biology, School of Health Science, Kyorin University, Hachioji, Tokyo 192-8508, Japan4

Received 4 February 2009/ Accepted 4 March 2009

Using comparative genome sequencing analysis, we identified a novel mutation in Bacillus subtilis that confers a low level of resistance to fusidic acid. This mutation was located in the mdtR (formerly yusO) gene, which encodes a MarR-type transcriptional regulator, and conferred a low level of resistance to several antibiotics, including novobiocin, streptomycin, and actinomycin D. Transformation experiments showed that this mdtR mutation was responsible for multidrug resistance. Northern blot analysis revealed that the downstream gene mdtP (formerly yusP), which encodes a multidrug efflux transporter, is cotranscribed with mdtR as an operon. Disruption of the mdtP gene completely abolished the multidrug resistance phenotype observed in the mdtR mutant. DNase I footprinting and primer extension analyses demonstrated that the MdtR protein binds directly to the mdtRP promoter, thus leading to repression of its transcription. Moreover, gel mobility shift analysis indicated that an Arg83 -> Lys or Ala67 -> Thr substitution in MdtR significantly reduces binding affinity to DNA, resulting in derepression of mdtRP transcription. Low concentrations of fusidic acid induced the expression of mdtP, although the level of mdtP expression was much lower than that in the mdtR disruptant. These findings indicate that the MdtR protein is a repressor of the mdtRP operon and that the MdtP protein functions as a multidrug efflux transporter in B. subtilis.

* Corresponding author. Mailing address: National Food Research Institute, 2-1-12 Kannondai, Tsukuba, Ibaraki 305-8642 Japan. Phone: 81-29-838-8125. Fax: 81-29-838-7996. E-mail: kochi{at}affrc.go.jp

{triangledown} Published ahead of print on 13 March 2009.

Journal of Bacteriology, May 2009, p. 3273-3281, Vol. 191, No. 10
0021-9193/09/$08.00+0     doi:10.1128/JB.00151-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Inaoka, T., Wang, G., Ochi, K. (2009). ScoC Regulates Bacilysin Production at the Transcription Level in Bacillus subtilis. J. Bacteriol. 191: 7367-7371 [Abstract] [Full Text]  


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