Mycobacterium tuberculosis Rv3160c is a TetR-like transcriptional repressor that regulates expression of the putative oxygenase Rv3161c

Autor:	Fredrik Almqvist, Christina L. Stallings, Saber Anoosheh, Gregory A. Harrison, Isabel Edström, Christer Larsson, Hasan Tükenmez, Souvik Sarkar, Anastasiia Kruchanova
Jazyk:	angličtina
Rok vydání:	2021
Předmět:	Oxygenase Infectious Medicine Science Antitubercular Agents Gene Expression Infektionsmedicin complex mixtures Article Target validation Microbiology Microbiology in the medical area Mycobacterium tuberculosis chemistry.chemical_compound Bacterial Proteins Target identification Tuberculosis Multidrug-Resistant Isoniazid medicine Mikrobiologi inom det medicinska området Tuberculosis TetR Gene Palindromic sequence Multidisciplinary biology Wild type Drug Resistance Microbial Gene Expression Regulation Bacterial Tetracycline biology.organism_classification Gene regulation Repressor Proteins chemistry Oxygenases Medicine lipids (amino acids peptides and proteins) DNA Protein Binding Transcription Factors medicine.drug
Zdroj:	Scientific Reports, Vol 11, Iss 1, Pp 1-10 (2021) Scientific Reports
ISSN:	2045-2322
Popis:	Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), is a major health threat listed among the top 10 causes of death worldwide. Treatment of multidrug-resistant Mtb requires use of additional second-line drugs that prolong the treatment process and result in higher death rates. Our team previously identified a 2-pyridone molecule (C10) that blocks tolerance to the first-line drug isoniazid at C10 concentrations that do not inhibit bacterial growth. Here, we discovered that the genes rv3160c and rv3161c are highly induced by C10, which led us to investigate them as potential targets. We show that Rv3160c acts as a TetR-like transcriptional repressor binding to a palindromic sequence located in the rv3161c promoter. We also demonstrate that C10 interacts with Rv3160c, inhibiting its binding to DNA. We deleted the rv3161c gene, coding for a putative oxygenase, to investigate its role in drug and stress sensitivity as well as C10 activity. This Δrv3161c strain was more tolerant to isoniazid and lysozyme than wild type Mtb. However, this tolerance could still be blocked by C10, suggesting that C10 functions independently of Rv3161c to influence isoniazid and lysozyme sensitivity.
Databáze:	OpenAIRE
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