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ACS Infect Dis. 2018 May 11;4(5):797-805. doi: 10.1021/acsinfecdis.7b00234. Epub 2018 Feb 13.

Detection of Bacteria-Specific Metabolism Using Hyperpolarized [2-13C]Pyruvate.

Author information

1
Department of Radiology and Biomedical Imaging , University of California, San Francisco , 1600 Fourth Street , Box 2520, San Francisco , California 94158 , United States.
2
Microbiology and Immunology , University of California, San Francisco , 600 16th Street , San Francisco , California 94158 , United States.
3
Department of Radiology , University of Virginia , 480 Ray C. Hunt Drive , Charlottesville , Virginia 22903 , United States.
4
Division of Infectious Diseases, School of Medicine , University of California, San Francisco , 505 Parnassus Avenue , San Francisco , California 94143 , United States.
5
Zuckerberg San Francisco General Hospital , 1001 Potrero Avenue , San Francisco , California 94110 , United States.

Abstract

The differentiation of bacterial infection from other causes of inflammation is difficult in clinical practice and is critical where patient outcomes rely heavily on early interventions. In addition to physical exam and laboratory markers, several imaging modalities are frequently employed, but these techniques generally target the host immune response, rather than the living microorganisms themselves. Here, we describe a method to detect bacteria-specific metabolism using hyperpolarized (HP) 13C magnetic resonance spectroscopy. This technology allows visualization of the real-time conversion of enriched 13C substrates to their metabolic products, identified by their distinct chemical shifts. We have identified the rapid metabolism of HP [2-13C]pyruvate to [1-13C]acetate as a metabolic signature of common bacterial pathogens. We demonstrate this conversion in representative Gram-negative and Gram-positive bacteria, namely, Escherichia coli and Staphylococcus aureus, and its absence in key mammalian cell types. Furthermore, this conversion was successfully modulated in three mutant strains, corresponding to deletions of relevant enzymes.

KEYWORDS:

acetate; bacterial metabolism; dynamic nuclear polarization (DNP); hyperpolarized 13C nuclear magnetic resonance (MR); pyruvate

PMID:
29405697
PMCID:
PMC6008482
DOI:
10.1021/acsinfecdis.7b00234
[Indexed for MEDLINE]
Free PMC Article

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