Rv0500A is a transcription factor that links Mycobacterium tuberculosis environmental response with division and impacts host colonization,Molecular Microbiology

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Rv0500A is a transcription factor that links Mycobacterium tuberculosis environmental response with division and impacts host colonization
Molecular Microbiology ( IF 2.6 ) Pub Date : 2022-02-15 , DOI: 10.1111/mmi.14886
Yuzo L Kevorkian _{1,

2} , Nathan J MacGilvary ₁ , David Giacalone _{1,

2} , Calvin Johnson ₁ , Shumin Tan _{1,

2}

Affiliation

For Mycobacterium tuberculosis (Mtb) to successfully infect a host, it must be able to adapt to changes in its microenvironment, including variations in ionic signals such as pH and chloride (Cl⁻), and link these responses to its growth. Transcriptional changes are a key mechanism for Mtb environmental adaptation, and we identify here Rv0500A as a novel transcriptional regulator that links Mtb environmental response and division processes. Global transcriptional profiling revealed that Rv0500A acts as a repressor and influences the expression of genes related to division, with the magnitude of its effect modulated by pH and Cl⁻. Rv0500A can directly bind the promoters of several of these target genes, and we identify key residues required for its DNA-binding ability and biological effect. Overexpression of rv0500A disrupted Mtb growth morphology, resulting in filamentation that was exacerbated by high environmental Cl⁻ levels and acidic pH. Finally, we show that perturbation of rv0500A leads to attenuation of the ability of Mtb to colonize its host in vivo. Our work highlights the important link between Mtb environmental response and growth characteristics, and uncovers a new transcription factor involved in this critical facet of Mtb biology.

中文翻译：

Rv0500A 是一种将结核分枝杆菌环境反应与分裂联系起来并影响宿主定植的转录因子

结核分枝杆菌(Mtb) 要成功感染宿主，它必须能够适应其微环境的变化，包括 pH 和氯化物 (Cl - ) 等离子信号的变化^，并将这些反应与其生长联系起来。转录变化是 Mtb 环境适应的关键机制，我们在此将 Rv0500A 确定为一种新型转录调节因子，将 Mtb 环境响应和分裂过程联系起来。全局转录谱显示 Rv0500A 作为阻遏物并影响与分裂相关的基因的表达，其作用的大小受 pH 和 Cl 调节^-. Rv0500A 可以直接结合其中几个靶基因的启动子，我们确定了其 DNA 结合能力和生物学效应所需的关键残基。rv0500A的过表达破坏了 Mtb 的生长形态，导致丝状化，高环境 Cl ^-水平和酸性 pH 值加剧了丝状化。最后，我们表明rv0500A的扰动导致 Mtb 在体内定殖其宿主的能力减弱。我们的工作突出了 Mtb 环境响应和生长特征之间的重要联系，并揭示了参与 Mtb 生物学这一关键方面的新转录因子。

更新日期：2022-02-15

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