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Maltodextrin-based imaging probes detect bacteria in vivo with high sensitivity and specificity

Nature Materials volume 10, pages 602–607 (2011)Cite this article

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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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Figure 1: In vivo detection of bacteria with MDPs.
Figure 2: Synthesis of MDP-1 and MDP-2.
Figure 3: MDPs have specificity for planktonic bacteria and bacterial biofilms.
Figure 4: MDP-2 images bacteria in vivo.
Figure 5: MDP-2 images bacteria in vivo using internalization through the maltodextrin transporter.

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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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Author notes

  1. Xinghai Ning and Seungjun Lee: These authors contributed equally to this work

Authors and Affiliations

  1. 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

    Xinghai Ning, Seungjun Lee, Dongin Kim & Niren Murthy

  2. Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia 30602, USA

    Zhirui Wang

  3. Department of Biology, Georgia State University, Atlanta, Georgia 30302, USA

    Bryan Stubblefield & Eric Gilbert

Authors
  1. Xinghai Ning
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Contributions

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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Correspondence to Seungjun Lee or Niren Murthy.

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The authors declare no competing financial interests.

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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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