Maltodextrin-based imaging probes detect bacteria in vivo with high sensitivity and specificity.
Maltodextrin-based imaging probes detect bacteria in vivo with high sensitivity and specificity.
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DOI：
10.1038/nmat3074
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发表时间：
2011-07-17
期刊：
影响因子：
41.2
通讯作者：
Murthy N
中科院分区：
文献类型：
--
作者：
Ning X;Lee S;Wang Z;Kim D;Stubblefield B;Gilbert E;Murthy N
细菌感染的诊断仍然是医学上的一个主要挑战。尽管许多造影剂已经被开发出来用于细菌成像，但它们的临床影响很小，因为它们不能检测体内的少量细菌，也不能将感染与其他病理（如癌症和炎症）区分开来。在这里，我们提出了一种造影剂家族，称为麦芽糖糊精成像探针（mdp），它可以检测体内细菌，灵敏度比以前报道的高两个数量级，并且可以使用独立于宿主反应和继发性病理的细菌特异性机制检测细菌。MDPs由一种与麦芽糖己糖偶联的荧光染料组成，并通过细菌特异性麦芽糖糊精转运途径快速内化，使MDPs具有对细菌高敏感性和特异性的独特组合。在这里，我们表明MDPs选择性地以毫摩尔浓度在细菌中积累，并且对细菌的特异性比哺乳动物细胞高1000倍。此外，我们证明MDPs可以在体内成像少至105个集落形成单位，并且可以区分活性细菌和由脂多糖或代谢不活跃的细菌诱导的炎症。
The diagnosis of bacterial infections remains a major challenge in medicine. Although numerous contrast agents have been developed to image bacteria, their clinical impact has been minimal because they are unable to detect small numbers of bacteria in vivo, and cannot distinguish infections from other pathologies such as cancer and inflammation. Here, we present a family of contrast agents, termed maltodextrin-based imaging probes (MDPs), which can detect bacteria in vivo with a sensitivity two orders of magnitude higher than previously reported, and can detect bacteria using a bacteria-specific mechanism that is independent of host response and secondary pathologies. MDPs are composed of a fluorescent dye conjugated to maltohexaose, and are rapidly internalized through the bacteria-specific maltodextrin transport pathway, endowing the MDPs with a unique combination of high sensitivity and specificity for bacteria. Here, we show that MDPs selectively accumulate within bacteria at millimolar concentrations, and are a thousand-fold more specific for bacteria than mammalian cells. Furthermore, we demonstrate that MDPs can image as few as 105 colony-forming units in vivo and can discriminate between active bacteria and inflammation induced by either lipopolysaccharides or metabolically inactive bacteria.
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