{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T21:25:57Z","timestamp":1793049957559,"version":"4.5.0"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2024,1,3]],"date-time":"2024-01-03T00:00:00Z","timestamp":1704240000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["310030_192724"],"award-info":[{"award-number":["310030_192724"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"name":"URMC University Research Award"},{"name":"NIH NIAID","award":["R21 AI69736"],"award-info":[{"award-number":["R21 AI69736"]}]},{"name":"NIH NIAMS","award":["P30 AR069655"],"award-info":[{"award-number":["P30 AR069655"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Staphylococcus aureus is the most common pathogen that causes implant-associated osteomyelitis, a clinically incurable disease. Immune evasion of S. aureus relies on various mechanisms to survive within the bone niche, including the secretion of leukotoxins such as Panton-Valentine leukocidin (PVL). PVL is a pore-forming toxin exhibiting selective human tropism for C5a receptors (C5aR1 and C5aR2) and CD45 on neutrophils, monocytes, and macrophages. PVL is an important virulence determinant in lung, skin and soft tissue infections. The involvement of PVL in S. aureus pathogenesis during bone infections has not been studied extensively yet. To investigate this, humanized BALB\/c Rag2\u2212\/\u2212Il2rg\u2212\/\u2212SirpaNODFlk2\u2212\/\u2212 (huBRGSF) mice were subjected to transtibial implant-associated osteomyelitis with community-acquired methicillin-resistant S. aureus (CA-MRSA) USA300 wild type strain (WT), an isogenic mutant lacking lukF\/S-PV (\u0394pvl), or complemented mutant (\u0394pvl+pvl). Three days post-surgery, \u0394pvl-infected huBRGSF mice had a less severe infection compared to WT-infected animals as characterized by 1) improved clinical outcomes, 2) lower ex vivo bacterial bone burden, 3) absence of staphylococcal abscess communities (SACs) in their bone marrow, and 4) compromised MRSA dissemination to internal organs (liver, kidney, spleen, heart). Interestingly, \u0394pvl-infected huBRGSF mice had fewer human myeloid cells, neutrophils, and HLA-DR+ monocytes in the bone niche compared to WT-infected animals. Expectedly, a smaller fraction of human myeloid cells were apoptotic in the \u0394pvl-infected huBRGSF animals. Taken together, our study highlights the pivotal role of PVL during acute implant-associated osteomyelitis in humanized mice.<\/jats:p>","DOI":"10.1093\/jbmrpl\/ziad005","type":"journal-article","created":{"date-parts":[[2024,1,3]],"date-time":"2024-01-03T20:28:58Z","timestamp":1704313738000},"source":"Crossref","is-referenced-by-count":18,"title":["Staphylococcus aureus Panton-Valentine Leukocidin worsens acute implant-associated osteomyelitis in humanized BRGSF mice"],"prefix":"10.1093","volume":"8","author":[{"given":"Marloes I","family":"Hofstee","sequence":"first","affiliation":[{"name":"AO Research Institute Davos , 7270 Davos , Switzerland"},{"name":"Department of Medical Microbiology and Infection Prevention , Amsterdam UMC, Amsterdam institute for Infection and Immunity, , 1105 AZ Amsterdam , The Netherlands"},{"name":"University of Amsterdam , Amsterdam UMC, Amsterdam institute for Infection and Immunity, , 1105 AZ Amsterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Siverino","sequence":"additional","affiliation":[{"name":"AO Research Institute Davos , 7270 Davos , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motoo","family":"Saito","sequence":"additional","affiliation":[{"name":"Center for Musculoskeletal Research, University of Rochester Medical Center , Rochester, NY 14642 , United States"},{"name":"Department of Orthopaedics and Rehabilitation, University of Rochester Medical Center , Rochester, NY 14618 , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Himanshu","family":"Meghwani","sequence":"additional","affiliation":[{"name":"Center for Musculoskeletal Research, University of Rochester Medical Center , Rochester, NY 14642 , United States"},{"name":"Department of Orthopaedics and Rehabilitation, University of Rochester Medical Center , Rochester, NY 14618 , United 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States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martijn","family":"Riool","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infection Prevention , Amsterdam UMC, Amsterdam institute for Infection and Immunity, , 1105 AZ Amsterdam , The Netherlands"},{"name":"University of Amsterdam , Amsterdam UMC, Amsterdam institute for Infection and Immunity, , 1105 AZ Amsterdam , The Netherlands"},{"name":"Department of Trauma Surgery, University Hospital Regensburg , 93053 Regensburg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Zeiter","sequence":"additional","affiliation":[{"name":"AO Research Institute Davos , 7270 Davos , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian A J","family":"Zaat","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infection Prevention , Amsterdam UMC, Amsterdam institute for Infection and Immunity, , 1105 AZ Amsterdam , The Netherlands"},{"name":"University of Amsterdam , Amsterdam UMC, Amsterdam institute for Infection and Immunity, , 1105 AZ Amsterdam , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T Fintan","family":"Moriarty","sequence":"additional","affiliation":[{"name":"AO Research Institute Davos , 7270 Davos , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7521-6154","authenticated-orcid":false,"given":"Gowrishankar","family":"Muthukrishnan","sequence":"additional","affiliation":[{"name":"Center for Musculoskeletal Research, University of Rochester Medical Center , Rochester, NY 14642 , United States"},{"name":"Department of Orthopaedics and Rehabilitation, University of Rochester Medical Center , Rochester, NY 14618 , United States"},{"name":"Department of Microbiology and Immunology, University of Rochester Medical Center , Rochester, NY 14642 , United 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