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Clinically,<jats:italic>S. aureus<\/jats:italic>osteomyelitis is associated with local inflammation, abscesses, aggressive osteolysis, and septic implant loosening. In contrast,<jats:italic>S. agalactiae<\/jats:italic>orthopaedic infections generally involve soft tissue, with acute life\u2010threatening vascular spread. While preclinical models that recapitulate the clinical features of<jats:italic>S. aureus<\/jats:italic>bone infection have proven useful for research, no animal models of<jats:italic>S. agalactiae<\/jats:italic>osteomyelitis exist. Here, we compared the pathology caused by these bacteria in an established murine model of implant\u2010associated osteomyelitis. In vitro scanning electron microscopy and CFU quantification confirmed similar implant inocula for both pathogens (~10<jats:sup>5<\/jats:sup>CFU\/pin). Assessment of mice at 14 days post\u2010infection demonstrated increased<jats:italic>S. aureus<\/jats:italic>virulence, as<jats:italic>S. agalactiae<\/jats:italic>infected mice had significantly greater body weight, and fewer CFU on the implant and in bone and adjacent soft tissue (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05). X\u2010ray, \u00b5CT, and histologic analyses showed that<jats:italic>S. agalactiae<\/jats:italic>induced significantly less osteolysis and implant loosening, and fewer large TRAP<jats:sup>+<\/jats:sup>osteoclasts than<jats:italic>S. aureus<\/jats:italic>without inducing intraosseous abscess formation. Most notably, transmission electron microscopy revealed that although both bacteria are capable of digesting cortical bone,<jats:italic>S. agalactiae<\/jats:italic>have a predilection for colonizing blood vessels embedded within cortical bone while<jats:italic>S. aureus<\/jats:italic>primarily colonizes the osteocyte lacuno\u2010canalicular network. This study establishes the first quantitative animal model of<jats:italic>S. agalactiae<\/jats:italic>osteomyelitis, and demonstrates a vasculotropic mode of<jats:italic>S. agalactiae<\/jats:italic>infection, in contrast to the osteotropic behavior of<jats:italic>S. aureus<\/jats:italic>osteomyelitis.<\/jats:p>","DOI":"10.1002\/jor.24962","type":"journal-article","created":{"date-parts":[[2020,12,18]],"date-time":"2020-12-18T17:15:56Z","timestamp":1608311756000},"page":"389-401","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Distinct vasculotropic versus osteotropic features of<i>S. agalactiae<\/i>versus<i>S. aureus<\/i>implant\u2010associated bone infection in mice"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9981-624X","authenticated-orcid":false,"given":"Elysia A.","family":"Masters","sequence":"first","affiliation":[{"name":"Center for Musculoskeletal Research University of Rochester Medical Center Rochester New York USA"},{"name":"Department of Biomedical Engineering University of Rochester Medical Center Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3760-8234","authenticated-orcid":false,"given":"Stephanie P.","family":"Hao","sequence":"additional","affiliation":[{"name":"Center for Musculoskeletal Research University of Rochester Medical Center Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0598-3232","authenticated-orcid":false,"given":"H. Mark","family":"Kenney","sequence":"additional","affiliation":[{"name":"Center for Musculoskeletal Research University of Rochester Medical Center Rochester New York USA"},{"name":"Department of Pathology and Laboratory Medicine University of Rochester Medical Center Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7674-1815","authenticated-orcid":false,"given":"Yugo","family":"Morita","sequence":"additional","affiliation":[{"name":"Center for Musculoskeletal Research University of Rochester Medical Center Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1978-7339","authenticated-orcid":false,"given":"Chad A.","family":"Galloway","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of Rochester Medical Center Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0176-1111","authenticated-orcid":false,"given":"Karen L.","family":"de Mesy Bentley","sequence":"additional","affiliation":[{"name":"Center for Musculoskeletal Research University of Rochester Medical Center Rochester New York USA"},{"name":"Department of Pathology and Laboratory Medicine University of Rochester Medical Center Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9384-4840","authenticated-orcid":false,"given":"Benjamin F.","family":"Ricciardi","sequence":"additional","affiliation":[{"name":"Center for Musculoskeletal Research University of Rochester Medical Center Rochester New York USA"},{"name":"Department of Orthopaedics and Rehabilitation University of Rochester Medical Center Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3587-4854","authenticated-orcid":false,"given":"Brendan F.","family":"Boyce","sequence":"additional","affiliation":[{"name":"Center for Musculoskeletal Research University of Rochester Medical Center Rochester New York USA"},{"name":"Department of Pathology and Laboratory Medicine University of Rochester Medical Center Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4854-9698","authenticated-orcid":false,"given":"Edward M.","family":"Schwarz","sequence":"additional","affiliation":[{"name":"Center for Musculoskeletal Research University of Rochester Medical Center Rochester New York USA"},{"name":"Department of Biomedical Engineering University of Rochester Medical Center Rochester New York USA"},{"name":"Department of Orthopaedics and Rehabilitation University of Rochester Medical Center Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2648-5849","authenticated-orcid":false,"given":"Irvin","family":"Oh","sequence":"additional","affiliation":[{"name":"Center for Musculoskeletal Research University of Rochester Medical Center Rochester New York USA"},{"name":"Department of Orthopaedics and Rehabilitation University of Rochester Medical Center Rochester New York 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