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

Hernandez, Frank JDepartment of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of of Iowa, Iowa City, IA, United States (författare)

Funding Agencies|AHA, National Institutes of Health; AI083211, NIAID, National Institutes of Health; AI083211, NIH, National Institutes of Health; AI101391, NIH, National Institutes of Health; NIH, National Institutes of Health
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. © 2014 Nature America, Inc.

Huang, LingyanIntegrated DNA Technologies (IDT), Coralville, IA, United States (författare)
Olson, Michael E.Department of Microbiology, Roy J. and Lucille A. Carver College of Medicine, University of of Iowa, Iowa City, IA, United States (författare)
Powers, Kristy M.Integrated DNA Technologies (IDT), Coralville, IA, United States (författare)
Hernandez, Luiza I.Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of of Iowa, Iowa City, IA, United States(Swepub:liu)luihe46 (författare)
Meyerholz, David K.Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, University of of Iowa, Iowa City, IA, United States (författare)
Thedens, Daniel R.Department of Radiology, Roy J. and Lucille A. Carver College of Medicine, University of of Iowa, Iowa City, IA, United States (författare)
Behlke, Mark A.Integrated DNA Technologies (IDT), Coralville, IA, United States (författare)
Horswill, Alexander R.Department of Microbiology, Roy J. and Lucille A. Carver College of Medicine, University of of Iowa, Iowa City, IA, United States (författare)
Mcnamara II, James O.Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of of Iowa, Iowa City, IA, United States (författare)
Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of of Iowa, Iowa City, IA, United StatesIntegrated DNA Technologies (IDT), Coralville, IA, United States (creator_code:org_t)

Ingår i:Nature Medicine: Nature Publishing Group20:3, s. 301-3061078-89561546-170X

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