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However, the relatively short emission wavelength of <jats:italic>lux<\/jats:italic> (peak 490\u2009nm) has limited tissue penetration. To overcome this limitation, the gene for the click beetle (<jats:italic>Pyrophorus plagiophtalamus<\/jats:italic>) red luciferase (<jats:italic>luc<\/jats:italic>) (with a longer &gt;600 emission wavelength), was introduced singly and in combination with the <jats:italic>lux<\/jats:italic> operon into a methicillin-resistant <jats:italic>S. aureus<\/jats:italic> strain. After administration of the substrate D-luciferin, the <jats:italic>luc<\/jats:italic> bioluminescent signal was substantially greater than the <jats:italic>lux<\/jats:italic> signal <jats:italic>in vitro<\/jats:italic>. The <jats:italic>luc<\/jats:italic> signal had enhanced tissue penetration and improved anatomical co-registration with infected internal organs compared with the <jats:italic>lux<\/jats:italic> signal in a mouse model of <jats:italic>S. aureus<\/jats:italic> bacteremia with a sensitivity of approximately 3\u2009\u00d7\u200910<jats:sup>4<\/jats:sup> CFU from the kidneys. Finally, in an <jats:italic>in vivo<\/jats:italic> mixed bacterial wound infection mouse model, <jats:italic>S. aureus luc<\/jats:italic> signals could be spectrally unmixed from <jats:italic>Pseudomonas aeruginosa lux<\/jats:italic> signals to noninvasively monitor the bacterial burden of both strains. Therefore, the <jats:italic>S. aureus luc<\/jats:italic> reporter may provide a technological advance for monitoring invasive organ dissemination during <jats:italic>S. aureus<\/jats:italic> bacteremia and for studying bacterial dynamics during mixed infections.<\/jats:p>","DOI":"10.1038\/s41598-019-52982-0","type":"journal-article","created":{"date-parts":[[2019,11,13]],"date-time":"2019-11-13T11:04:01Z","timestamp":1573643041000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Development of a Staphylococcus aureus reporter strain with click beetle red luciferase for enhanced in vivo imaging of experimental bacteremia\u00a0and mixed infections"],"prefix":"10.1038","volume":"9","author":[{"given":"Robert J.","family":"Miller","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi A.","family":"Crosby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin","family":"Schilcher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger V.","family":"Ortines","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Momina","family":"Mazhar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dustin A.","family":"Dikeman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bret L.","family":"Pinsker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle D.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel P.","family":"Joyce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8212-8985","authenticated-orcid":false,"given":"Nathan K.","family":"Archer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3447-1284","authenticated-orcid":false,"given":"Martin P.","family":"Alphonse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Czupryna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William R.","family":"Anderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas M.","family":"Bernthal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea","family":"Fortuno-Miranda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff W. 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