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• W2519684389 abstract "Toward the development of a passive immunization toprevent implant-associated Staphylococcus aureus osteomyelitis inpatients undergoing total joint replacement surgery, here weevaluated the effects of a candidate anti-glucosaminidase (Gmd)mAb (1C11) in vitro and in vivo. Using our highly reproduciblemurine model of implantassociated osteomyelitis, we observed areduced severity of infection in mice that received 1C11 one dayprior to challenge with the bacterial inoculum, and demonstratedthat tibiae explanted from these protected mice at day 14post-infection were void of a necrotic sequestrum and had anoverall reduced osteolytic lesion at the site of pin insertion. Wealso established the presence of defective biofilms on the surfaceof explanted pins from the 1C11 immunized and ΔGmd challengedmice, presumably from inhibited colonization of the implantsurfaces. In vitro, 1C11 had no direct effects on proliferation,but electron microscopy demonstrated that anti-Gmd mAb phenocopiesΔGmd defects in binary fission. Additionally, 1C11 treated samplesexhibited a roughtextured cell wall surface morphology studdedwith small knob-like structures, similar to bacteria treated withsubinhibitory concentrations of vancomycin. In vitro analyses tounderstand the mechanism of action demonstrated that prolongedtreatment (4 hours) with 1C11 promotes the formation of largeclusters (“megaclusters”), of which increased their own degree ofopsonophagocytosis by mouse macrophages. Collectively, these datasuggest that anti-Gmd mAb may enhance the host innate immuneresponse to S. aureus infection, therefore reducing bacterialspread and the overall severity of infection." @default.
• W2519684389 created "2016-09-23" @default.
• W2519684389 creator A5026987301 @default.
• W2519684389 date "2014-01-01" @default.
• W2519684389 modified "2023-09-26" @default.
• W2519684389 title "Evaluation of Anti-Glucosaminidase Monoclonal Antibodies as a Passive Vaccination for Implant-Associated Staphylococcus aureus Osteomyelitis" @default.
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