Mycobacterium tuberculosis Rv3160c is a TetR-like transcriptional repressor that regulates expression of the putative oxygenase Rv3161c.
Mycobacterium tuberculosis Rv3160c is a TetR-like transcriptional repressor that regulates expression of the putative oxygenase Rv3161c.
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DOI：
10.1038/s41598-021-81104-y
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发表时间：
2021-01-15
影响因子：
4.6
通讯作者：
Larsson C
中科院分区：
文献类型：
--
作者：
Tükenmez H;Sarkar S;Anoosheh S;Kruchanova A;Edström I;Harrison GA;Stallings CL;Almqvist F;Larsson C
由结核分枝杆菌（Mtb）引起的结核病是全球十大死亡原因之一。耐多药结核病的治疗需要使用额外的二线药物，这会延长治疗过程并导致更高的死亡率。我们的团队先前确定了一种2-吡啶酮分子（C10），它在不抑制细菌生长的C10浓度下阻断了对一线药物异烟肼的耐受性。在这里，我们发现基因rv 3160 c和rv 3161 c被C10高度诱导，这使得我们将它们作为潜在的靶点进行研究。我们发现，Rv 3160 c作为一个TetR样的转录抑制因子结合到位于rv 3161 c启动子的回文序列。我们还证明了C10与Rv 3160 c相互作用，抑制其与DNA的结合。我们删除了rv 3161 c基因，编码一个假定的加氧酶，以研究其在药物和应激敏感性以及C10活性中的作用。Δ rv 3161 c菌株对异烟肼和溶菌酶的耐受性高于野生型Mtb。然而，这种耐受性仍然可以被C10阻断，这表明C10的功能独立于Rv 3161 c来影响异烟肼和溶菌酶的敏感性。
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.
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影响因子：
4.6
作者：
Gomez A;Andreu N;Ferrer-Navarro M;Yero D;Gibert I
通讯作者：
Gibert I
DOI：
10.1111/j.1432-1033.1988.tb13761.x
发表时间：
1988-01-15
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
SAMWORTH, CM;DEGLIESPOSTI, M;LENAZ, G
通讯作者：
LENAZ, G
影响因子：
3.7
作者：
Dutta NK;Mehra S;Kaushal D
通讯作者：
Kaushal D
影响因子：
8.8
作者：
Cortes T;Schubert OT;Rose G;Arnvig KB;Comas I;Aebersold R;Young DB
通讯作者：
Young DB
影响因子：
5.6
作者：
Orth, P;Cordes, F;Hinrichs, W
通讯作者：
Hinrichs, W