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Research Article

Duplex DNA-Invading γ-Modified Peptide Nucleic Acids Enable Rapid Identification of Bloodstream Infections in Whole Blood

Jörk Nölling, Srinivas Rapireddy, Joel I. Amburg, Elizabeth M. Crawford, Ranjit A. Prakash, Arthur R. Rabson, Yi-Wei Tang, Alon Singer
Martin J. Blaser, Editor
Jörk Nölling
HelixBind, Inc., Marlborough, Massachusetts, USA
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Srinivas Rapireddy
HelixBind, Inc., Marlborough, Massachusetts, USA
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Joel I. Amburg
HelixBind, Inc., Marlborough, Massachusetts, USA
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Elizabeth M. Crawford
HelixBind, Inc., Marlborough, Massachusetts, USA
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Ranjit A. Prakash
HelixBind, Inc., Marlborough, Massachusetts, USA
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Arthur R. Rabson
Department of Pathology and Laboratory Medicine, Tufts University School of Medicine, Clinical Immunology and Microbiology Laboratories, Tufts Medical Center, Boston, Massachusetts, USA
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Yi-Wei Tang
Department of Laboratory Medicine, Memorial Sloan-Kettering Cancer Center, Weill Medical College of Cornell University, New York, New York, USADepartment of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, New York, USA
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Alon Singer
HelixBind, Inc., Marlborough, Massachusetts, USA
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Martin J. Blaser
New York University
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Kurt Reed
University of Wisconsin School of Medicine and Public Health
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Charles Stratton
Vanderbilt University Medical Center
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DOI: 10.1128/mBio.00345-16
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ABSTRACT

Bloodstream infections are a leading cause of morbidity and mortality. Early and targeted antimicrobial intervention is lifesaving, yet current diagnostic approaches fail to provide actionable information within a clinically viable time frame due to their reliance on blood culturing. Here, we present a novel pathogen identification (PID) platform that features the use of duplex DNA-invading γ-modified peptide nucleic acids (γPNAs) for the rapid identification of bacterial and fungal pathogens directly from blood, without culturing. The PID platform provides species-level information in under 2.5 hours while reaching single-CFU-per-milliliter sensitivity across the entire 21-pathogen panel. The clinical utility of the PID platform was demonstrated through assessment of 61 clinical specimens, which showed >95% sensitivity and >90% overall correlation to blood culture findings. This rapid γPNA-based platform promises to improve patient care by enabling the administration of a targeted first-line antimicrobial intervention.

IMPORTANCE Bloodstream infections continue to be a major cause of death for hospitalized patients, despite significant improvements in both the availability of treatment options as well their application. Since early and targeted antimicrobial intervention is one of the prime determinants of patient outcome, the rapid identification of the pathogen can be lifesaving. Unfortunately, current diagnostic approaches for identifying these infections all rely on time-consuming blood culture, which precludes immediate intervention with a targeted antimicrobial. To address this, we have developed and characterized a new and comprehensive methodology, from patient specimen to result, for the rapid identification of both bacterial and fungal pathogens without the need for culturing. We anticipate broad interest in our work, given the novelty of our technical approach combined with an immense unmet need.

FOOTNOTES

    • Received 2 March 2016
    • Accepted 15 March 2016
    • Published 19 April 2016
  • Copyright © 2016 Nölling et al.

This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

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Duplex DNA-Invading γ-Modified Peptide Nucleic Acids Enable Rapid Identification of Bloodstream Infections in Whole Blood
Jörk Nölling, Srinivas Rapireddy, Joel I. Amburg, Elizabeth M. Crawford, Ranjit A. Prakash, Arthur R. Rabson, Yi-Wei Tang, Alon Singer
mBio Apr 2016, 7 (2) e00345-16; DOI: 10.1128/mBio.00345-16

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Duplex DNA-Invading γ-Modified Peptide Nucleic Acids Enable Rapid Identification of Bloodstream Infections in Whole Blood
Jörk Nölling, Srinivas Rapireddy, Joel I. Amburg, Elizabeth M. Crawford, Ranjit A. Prakash, Arthur R. Rabson, Yi-Wei Tang, Alon Singer
mBio Apr 2016, 7 (2) e00345-16; DOI: 10.1128/mBio.00345-16
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