Abstract
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 inflammation1,2,3,4,5,6,7. 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 pathway8,9,10,11, 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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Acknowledgements
This project has been funded in whole or in part with Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN268201000043C, NSF-BES-0546962 Career Award (N.M.) and NIH RO1 HL096796-01 (N.M.).
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X.N. synthesized and characterized MDP-1 and MDP-2, designed and analysed experiments, and wrote the manuscript. S.L. designed, carried out and analysed experiments, and contributed to the writing of the manuscript. Z.W. performed MS experiments to characterize all intermediates and final products and proof read the manuscript. D.K. carried out in vitro experiments. B.S. prepared biofilms and performed confocal laser scanning microscopy. E.G. supervised the preparation of biofilms and proof read the manuscript. N.M. designed and supervised the project and contributed to the writing of the manuscript.
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Ning, X., Lee, S., Wang, Z. et al. Maltodextrin-based imaging probes detect bacteria in vivo with high sensitivity and specificity. Nature Mater 10, 602–607 (2011). https://doi.org/10.1038/nmat3074
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DOI: https://doi.org/10.1038/nmat3074
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