Noninvasive imaging of Staphylococcus aureus infections with a nuclease-activated probe.
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.
Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
Frank J
FJ
Hernandez
Integrated DNA Technologies (IDT), Coralville, Iowa, USA.
Lingyan
L
Huang
Department of Microbiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
Michael E
ME
Olson
Integrated DNA Technologies (IDT), Coralville, Iowa, USA.
Kristy M
KM
Powers
Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
Luiza I
LI
Hernandez
Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
David K
DK
Meyerholz
Department of Radiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
Daniel R
DR
Thedens
Integrated DNA Technologies (IDT), Coralville, Iowa, USA.
Mark A
MA
Behlke
Department of Microbiology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
Alexander R
AR
Horswill
Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
James O
JO
McNamara
D000818:Animals; D001435:Bacteriophages / Q000378:metabolism; D005260:Female; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000737:chemistry; D007700:Kinetics; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D008836:Micrococcal Nuclease / Q000737:chemistry*; D015345:Oligonucleotide Probes / Q000737:chemistry; D009841:Oligonucleotides / Q000737:chemistry; D052880:Pyomyositis / Q000175:diagnosis / Q000382:microbiology; D013203:Staphylococcal Infections / Q000175:diagnosis* / Q000473:pathology*
D005456:Fluorescent Dyes; D015345:Oligonucleotide Probes; D009841:Oligonucleotides; D008836:Micrococcal Nuclease