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

[pyomyositis]

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 .