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Multiple antibiotic resistance and severe clinical outcomes provide a strong rationale for development of immunoglobulin-based strategies. Traditionally, novel immunological approaches against bacterial pathogens involve antibodies directed against cell surface-exposed virulence-associated epitopes or toxins. In this study, we generated a monoclonal antibody targeting the housekeeping protein IsaA, a suggested soluble lytic transglycosylase of\n            <jats:italic>S. aureus<\/jats:italic>\n            , and tested its therapeutic efficacy in two experimental mouse infection models. A murine anti-IsaA antibody of the IgG1 subclass (UK-66P) showed the highest binding affinity in Biacore analysis. This antibody recognized all\n            <jats:italic>S. aureus<\/jats:italic>\n            strains tested, including hospital-acquired and community-acquired methicillin-resistant\n            <jats:italic>S. aureus<\/jats:italic>\n            strains. Therapeutic efficacy\n            <jats:italic>in vivo<\/jats:italic>\n            in mice was analyzed using a central venous catheter-related infection model and a sepsis survival model. In both models, anti-IsaA IgG1 conferred protection against staphylococcal infection.\n            <jats:italic>Ex vivo<\/jats:italic>\n            , UK-66P activates professional phagocytes and induces highly microbicidal reactive oxygen metabolites in a dose-dependent manner, resulting in bacterial killing. The study provides proof of concept that monoclonal IgG1 antibodies with high affinity to the ubiquitously expressed, single-epitope-targeting IsaA are effective in the treatment of staphylococcal infection in different mouse models. Anti-IsaA antibodies might be a useful component in an antibody-based therapeutic for prophylaxis or adjunctive treatment of human cases of\n            <jats:italic>S. aureus<\/jats:italic>\n            infections.\n          <\/jats:p>","DOI":"10.1128\/aac.01144-10","type":"journal-article","created":{"date-parts":[[2010,10,19]],"date-time":"2010-10-19T03:54:41Z","timestamp":1287460481000},"page":"165-173","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":55,"title":["Functional Antibodies Targeting IsaA of\n            <i>Staphylococcus aureus<\/i>\n            Augment Host Immune Response and Open New Perspectives for Antibacterial Therapy"],"prefix":"10.1128","volume":"55","author":[{"given":"Udo","family":"Lorenz","sequence":"first","affiliation":[{"name":"Department of General, Visceral, Vascular and Paediatric Surgery, University Clinic of Wuerzburg, Oberdu\u0308rrbacher Str. 6, 97080 Wuerzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Birgit","family":"Lorenz","sequence":"additional","affiliation":[{"name":"Institute for Molecular Infection Biology, University of Wuerzburg, Josef-Schneider-Str. 2, 97080 Wuerzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tim","family":"Schmitter","sequence":"additional","affiliation":[{"name":"Institute for Molecular Infection Biology, University of Wuerzburg, Josef-Schneider-Str. 2, 97080 Wuerzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karin","family":"Streker","sequence":"additional","affiliation":[{"name":"Institute for Molecular Infection Biology, University of Wuerzburg, Josef-Schneider-Str. 2, 97080 Wuerzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Erck","sequence":"additional","affiliation":[{"name":"Helmholtz Centre for Infection Research, Inhoffenstra\u00dfe 7, 38124 Braunschweig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ju\u0308rgen","family":"Wehland","sequence":"additional","affiliation":[{"name":"Helmholtz Centre for Infection Research, Inhoffenstra\u00dfe 7, 38124 Braunschweig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joachim","family":"Nickel","sequence":"additional","affiliation":[{"name":"Department of Physiological Chemistry II, Biocenter, University of Wuerzburg, Am Hubland, 97074 Wuerzburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bastian","family":"Zimmermann","sequence":"additional","affiliation":[{"name":"Biaffin GmbH and Co. 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