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

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 mycobacter...

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Bibliographic Details
Published in:Biochemistry (Moscow) 2019-05, Vol.84 (5), p.540-552
Main Authors: Zhou, L., He, Z.-G., Li, W.
Format: Article
Language:English
Subjects:
Actinomycetes
Analysis
Antibiotic resistance
Antibiotics
Arabinogalactan
Arabinose
Biochemistry
Biomedical and Life Sciences
Biomedicine
Bioorganic Chemistry
Cell walls
Control
Dosage and administration
Drug resistance
Drug therapy
Isoniazid
Life Sciences
Microbial drug resistance
Microbiology
Mycobacterium smegmatis
Mycobacterium tuberculosis
Permeability
Regulatory mechanisms (biology)
Resistance factors
Sugar
Transcription factors
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Summary: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.
ISSN:0006-2979
1608-3040
DOI:10.1134/S0006297919050080