High-resolution plasma metabolomics analysis to detect Mycobacterium tuberculosis-associated metabolites that distinguish active pulmonary tuberculosis in humans.
High-resolution plasma metabolomics analysis to detect Mycobacterium tuberculosis-associated metabolites that distinguish active pulmonary tuberculosis in humans.
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DOI：
10.1371/journal.pone.0205398
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Ziegler TR
中科院分区：
文献类型：
--
作者：
Collins JM;Walker DI;Jones DP;Tukvadze N;Liu KH;Tran VT;Uppal K;Frediani JK;Easley KA;Shenvi N;Khadka M;Ortlund EA;Kempker RR;Blumberg HM;Ziegler TR
肺结核(TB)是一个主要的世界性健康问题，缺乏强有力的血液生物标志物来检测活动性疾病。高分辨率代谢组学(HRM)是一种发现低丰度代谢物作为诊断结核病的血液生物标志物的创新方法，包括那些已知由致病微生物结核分枝杆菌(Mtb)产生的代谢产物。我们使用HRM图谱来测量17名患有活动性肺结核病的成年人和16名没有活动性肺结核的家庭接触者的血浆代谢组。我们使用一种可疑的筛选方法，根据保留时间和准确的质量匹配来鉴定之前在结核分枝杆菌细胞培养研究中描述的代谢物。活动性结核病患者与其家庭接触者的相对代谢物丰度的相关性预测，根据准确的质量匹配，活动性结核病患者中有三种与结核分枝杆菌相关的代谢物显著增加：磷脂酰甘油(PG)(16：0-18：1)、溶血磷脂酰肌醇(Lyso-PI)(18：0)和酰基磷脂酰肌醇甘露糖苷(Ac1PIM1)(56：1)(p<；共0.001)。这三种代谢产物对活动性肺结核的分类准确率很高(AUC=0.97)。离子解离谱(串联MS/MS)支持活动性肺结核患者血浆中PG(16：0~18：1)和Lyso-PI(18：0)的鉴定，但Ac1PIM1的鉴定不能确定。血浆中结核分枝杆菌相关脂代谢产物PG(16：0~18：1)和Lyso-PI(18：0)的存在可准确识别活动性肺结核患者。体外和体内数据的一致性表明，在未来的研究中探索这些数据作为结核病生物标记物的可能性是合适的。
Pulmonary tuberculosis (TB) is a major worldwide health problem that lacks robust blood-based biomarkers for detection of active disease. High-resolution metabolomics (HRM) is an innovative method to discover low-abundance metabolites as putative blood biomarkers to detect TB disease, including those known to be produced by the causative organism, Mycobacterium tuberculosis (Mtb). We used HRM profiling to measure the plasma metabolome for 17 adults with active pulmonary TB disease and 16 of their household contacts without active TB. We used a suspect screening approach to identify metabolites previously described in cell culture studies of Mtb based on retention time and accurate mass matches. The association of relative metabolite abundance in active TB disease subjects compared to their household contacts predicted three Mtb-associated metabolites that were significantly increased in the active TB patients based on accurate mass matches: phosphatidylglycerol (PG) (16:0_18:1), lysophosphatidylinositol (Lyso-PI) (18:0) and acylphosphatidylinositol mannoside (Ac1PIM1) (56:1) (p<0.001 for all). These three metabolites provided excellent classification accuracy for active TB disease (AUC = 0.97). Ion dissociation spectra (tandem MS/MS) supported the identification of PG (16:0_18:1) and Lyso-PI (18:0) in the plasma of patients with active TB disease, though the identity of Ac1PIM1 could not be definitively confirmed. Presence of the Mtb-associated lipid metabolites PG (16:0_18:1) and Lyso-PI (18:0) in plasma accurately identified patients with active TB disease. Consistency of in vitro and in vivo data suggests suitability for exploring these in future studies for possible development as TB disease biomarkers.
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用于结核分枝杆菌化学分类学分析的比较脂质组学平台。
影响因子：
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Layre E;Sweet L;Hong S;Madigan CA;Desjardins D;Young DC;Cheng TY;Annand JW;Kim K;Shamputa IC;McConnell MJ;Debono CA;Behar SM;Minnaard AJ;Murray M;Barry CE 3rd;Matsunaga I;Moody DB
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Moody DB