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Biochemistry (Moscow)

, Volume 84, Issue 5, pp 540–552 | Cite as

AraR, an L-Arabinose-Responding Transcription Factor, Negatively Regulates Resistance of Mycobacterium smegmatis to Isoniazid

  • L. Zhou
  • Z.-G. He
  • W. LiEmail author
Article
  • 3 Downloads

Abstract

L-Arabinose is an important component of mycobacterial cell wall. L-Arabinose is involved in the synthesis of arabinogalactan, lipoarabinomannan, and other sugar compounds, which suggests that it can modulate cell wall permeability and drug resistance. However, whether L-arabinose affects mycobacterial antibiotic resistance and the underlying regulatory mechanism remains unclear. In this study, we characterized a new transcription factor of Mycobacterium smegmatis, AraR, that responds to L-arabinose and regulates mycobacterial sensitivity to isoniazid (INH). AraR specifically recognizes two conserved 15-bp motifs within the upstream regulatory region of the arabinose (araR) operon. AraR functions as a transcriptional repressor that negatively regulates araR expression. In contrast to the effect of AraR, overexpression of the araR operon contributes to the mycobacterial INH resistance. L-arabinose acts as an effector and derepresses transcriptional inhibition by AraR. The araR-deficient strain is more resistant to INH than the wild-type strain, whereas the araR-overexpressing strain is more sensitive to INH. Addition of L-arabinose to the medium can significantly increase the resistance to INH of the wild-type strain, but not of the araR knockout strain. Therefore, we identified a new L-arabinose-responding transcription factor and revealed its effect on the bacterial antibiotic resistance. These findings can provide new insights in the regulatory mechanisms mediated by sugar molecules and their relationship with drug resistance in mycobacteria.

Keywords

AraR mycobacteria L-arabinose antibiotic resistance 

Abbreviations

AraR

a LacI family transcription factor encoded by Ms1708

ChIP

chromatin immunoprecipitation

EMSA

electrophoretic mobility shift assay

INH

isoniazid

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Copyright information

© Pleiades Publishing, Ltd. 2019

Authors and Affiliations

  1. 1.National Key Laboratory of Agricultural Microbiology, College of Life Science and TechnologyHuazhong Agricultural UniversityWuhanChina
  2. 2.State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Life Science and TechnologyGuangxi UniversityNanningChina

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