Reproducibility of the Ribosomal RNA Synthesis Ratio in Sputum and Association with Markers of Mycobacterium tuberculosis Burden.
Reproducibility of the Ribosomal RNA Synthesis Ratio in Sputum and Association with Markers of Mycobacterium tuberculosis Burden.
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痰液中核糖体RNA合成率的重现性及其与结核分枝杆菌负荷标志物的相关性
DOI：
10.1128/spectrum.00481-21
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发表时间：
2021-10-31
影响因子：
3.7
通讯作者：
Walter ND
中科院分区：
文献类型：
--
作者：
Musisi E;Dide-Agossou C;Al Mubarak R;Rossmassler K;Ssesolo AW;Kaswabuli S;Byanyima P;Sanyu I;Zawedde J;Worodria W;Voskuil MI;Savic RM;Nahid P;Davis JL;Huang L;Moore CM;Walter ND
迫切需要改进用于人类结核病 (TB) 药物试验的药效学标记物。结核病的药效学监测通常使用培养或分子方法来计算痰中结核分枝杆菌的负荷。最近提出的一种名为 rRNA 合成 (RS) 比率的测定方法可测量一种全新的特性，即药物如何影响正在进行的细菌 rRNA 合成。在这里，我们通过测试 38 名患有药物敏感肺结核的乌干达成人的治疗前痰液，评估了 RS 比率作为潜在药效监测工具的作用。我们量化了配对预处理痰液中的 RS 比率，并评估了 RS 比率与结核分枝杆菌负荷的微生物和分子标志物之间的关系。我们发现痰样本中的 RS 比率具有高度的重复性和重现性。 RS 比率与结核分枝杆菌负担无关，证实它测量的是一种独特的新特性。相反，结核分枝杆菌负荷的标志物彼此密切相关。这些结果表明 RS 比率是可重复和可再现的，并提供了来自结核分枝杆菌负荷标记的独特类型的信息。重要性 这项研究朝着新型药效标记物的实际应用迈出了重要一步，我们相信该标记物将对结核病产生变革性影响。本文遵循我们最近在 Nature Communications 上发表的报告，即一种称为 rRNA 合成 (RS) 比率的测定表明药物和治疗方案的治疗缩短。与传统的细菌负荷测量不同，RS 比率测量的是一种全新的特性，即药物如何影响正在进行的细菌 rRNA 合成。
There is a critical need for improved pharmacodynamic markers for use in human tuberculosis (TB) drug trials. Pharmacodynamic monitoring in TB has conventionally used culture or molecular methods to enumerate the burden of Mycobacterium tuberculosis organisms in sputum. A recently proposed assay called the rRNA synthesis (RS) ratio measures a fundamentally novel property, how drugs impact ongoing bacterial rRNA synthesis. Here, we evaluated RS ratio as a potential pharmacodynamic monitoring tool by testing pretreatment sputa from 38 Ugandan adults with drug-susceptible pulmonary TB. We quantified the RS ratio in paired pretreatment sputa and evaluated the relationship between the RS ratio and microbiologic and molecular markers of M. tuberculosis burden. We found that the RS ratio was highly repeatable and reproducible in sputum samples. The RS ratio was independent of M. tuberculosis burden, confirming that it measures a distinct new property. In contrast, markers of M. tuberculosis burden were strongly associated with each other. These results indicate that the RS ratio is repeatable and reproducible and provides a distinct type of information from markers of M. tuberculosis burden. IMPORTANCE This study takes a major next step toward practical application of a novel pharmacodynamic marker that we believe will have transformative implications for tuberculosis. This article follows our recent report in Nature Communications that an assay called the rRNA synthesis (RS) ratio indicates the treatment-shortening of drugs and regimens. Distinct from traditional measures of bacterial burden, the RS ratio measures a fundamentally novel property, how drugs impact ongoing bacterial rRNA synthesis.
影响因子：
3.7
作者：
Davis JL;Worodria W;Kisembo H;Metcalfe JZ;Cattamanchi A;Kawooya M;Kyeyune R;den Boon S;Powell K;Okello R;Yoo S;Huang L
通讯作者：
Huang L