The Wallace H. Coulter Department of Biomedical Engineering and the Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia 30332, USA.
Nat Mater. 2011 Jul 17;10(8):602-7. doi: 10.1038/nmat3074.
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 10(5) colony-forming units in vivo and can discriminate between active bacteria and inflammation induced by either lipopolysaccharides or metabolically inactive bacteria.
细菌感染的诊断仍然是医学上的一大挑战。尽管已经开发出许多对比剂来对细菌进行成像,但由于它们无法在体内检测到少量的细菌,并且无法将感染与癌症和炎症等其他病理区分开来,因此它们的临床影响微乎其微。在这里,我们提出了一类称为麦芽糊精基成像探针(MDPs)的对比剂,它们可以以比以前报道的灵敏度高两个数量级的方式在体内检测到细菌,并且可以使用一种细菌特异性机制来检测细菌,该机制独立于宿主反应和继发病理。MDPs 由荧光染料与麦芽六糖缀合而成,通过细菌特异性的麦芽糊精转运途径迅速内化,使 MDPs 具有高灵敏度和特异性的独特组合。在这里,我们表明 MDPs 可以在毫摩尔浓度下选择性地在细菌内积累,并且对细菌的特异性比哺乳动物细胞高一千倍。此外,我们证明 MDPs 可以在体内对低至 10^5 个菌落形成单位进行成像,并可以区分活性细菌和由脂多糖或代谢不活跃的细菌引起的炎症。