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Evaluation of Anti-Glucosaminidase Monoclonal Antibodies as a Passive Immunization for Methicillin-Resistant Staphylococcus aureus ( MRSA ) Osteomyelitis

INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) has surpassed HIV as the most deadly pathogen in the United States, and accounts for over 100,000 deaths per year world wide. In Orthopaedics there is great concern over the very poor outcomes of twostage revision total joint replacement (TJR) surgery from MRSA osteomyelitis (OM), which has a 30-50% failure rate. Thus, nontraditional interventions like passive immunization are warranted, particularly for immunocompromised patients and the elderly who are typically poor responders to active vaccines. Previously, we identified the S. aureus peptidoglycan hydrolase glucosaminidase (Gmd) as a protective antigen in a murine model of implant-associated OM. Since this enzyme is essential for cell wall digestion during bacterial growth, and no significant genetic variation has been identified among all clinical strains, we hypothesized that effective anti-Gmd antibodies would have multiple mechanisms of action, including promotion of opsonophagocytosis and direct inhibition of enzyme function. Thus, the aims of this study were to evaluate the activities of a high affinity IgG1 anti-Gmd monoclonal antibody (1C11) in vitro and in vivo.