Noninvasive imaging of Staphylococcus aureus infections with a nuclease-activated probe

Frank J Hernandez; Lingyan Huang; Michael E Olson; Kristy M Powers; Luiza I Hernandez; David K Meyerholz; Daniel R Thedens; Mark A Behlke; Alexander R Horswill; James O McNamara II

doi:10.1038/nm.3460

Back

Noninvasive imaging of Staphylococcus aureus infections with a nuclease-activated probe

Journal article

Peer reviewed

Noninvasive imaging of Staphylococcus aureus infections with a nuclease-activated probe

Frank J Hernandez, Lingyan Huang, Michael E Olson, Kristy M Powers, Luiza I Hernandez, David K Meyerholz, Daniel R Thedens, Mark A Behlke, Alexander R Horswill and James O McNamara II

Nature medicine, Vol.20(3), pp.301-306

03/2014

DOI: 10.1038/nm.3460

PMCID: PMC3949172

PMID: 24487433

Files and links (1)

url

https://www.ncbi.nlm.nih.gov/pmc/articles/3949172View

Open Access

Abstract

Technologies that enable the rapid detection and localization of bacterial infections in living animals could address an unmet need for infectious disease diagnostics. We describe a molecular imaging approach for the specific, noninvasive detection of S. aureus based on the activity of the S. aureus secreted nuclease, micrococcal nuclease (MN). Several short synthetic oligonucleotides, rendered resistant to mammalian serum nucleases by various chemical modifications and flanked with a fluorophore and quencher, were activated upon degradation by purified MN and in S. aureus culture supernatants. A probe consisting of a pair of deoxythymidines flanked by several 2'-O-methyl-modified nucleotides was activated in culture supernatants of S. aureus but not in culture supernatants of several other pathogenic bacteria. Systemic administration of this probe to mice bearing S. aureus muscle infections resulted in probe activation at the infection sites in an MN-dependent manner. This new bacterial imaging approach has potential clinical applicability for infections with S. aureus and several other medically important pathogens.

Fluorescence

Magnetic Resonance Imaging

Fluorescent Dyes - chemistry

Oligonucleotides - chemistry

Pyomyositis - diagnosis

Staphylococcal Infections - pathology

Mice, Inbred C57BL

Pyomyositis - microbiology

Staphylococcal Infections - diagnosis

Animals

Bacteriophages - metabolism

Female

Mice

Kinetics

Oligonucleotide Probes - chemistry

Micrococcal Nuclease - chemistry

Details

Title: Subtitle: Noninvasive imaging of Staphylococcus aureus infections with a nuclease-activated probe
Creators: Frank J Hernandez - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
Lingyan Huang - Integrated DNA Technologies (IDT), Coralville, Iowa, USA
Michael E Olson - Department of Microbiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
Kristy M Powers - Integrated DNA Technologies (IDT), Coralville, Iowa, USA
Luiza I Hernandez - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
David K Meyerholz - Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
Daniel R Thedens - Department of Radiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
Mark A Behlke - Integrated DNA Technologies (IDT), Coralville, Iowa, USA
Alexander R Horswill - Department of Microbiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
James O McNamara II - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
Resource Type: Journal article
Publication Details: Nature medicine, Vol.20(3), pp.301-306
DOI: 10.1038/nm.3460
PMID: 24487433
PMCID: PMC3949172
NLM abbreviation: Nat Med
ISSN: 1078-8956
eISSN: 1546-170X
Grant note: AI083211 / NIAID NIH HHS R21 AI101391 / NIAID NIH HHS P01 AI083211 / NIAID NIH HHS AI101391 / NIAID NIH HHS R01 AI106738 / NIAID NIH HHS
Language: English
Date published: 03/2014
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Radiology; Electrical and Computer Engineering; Pathology; Internal Medicine
Record Identifier: 9984083804402771

Metrics

20 Record Views

95 Times Cited - Web of Science