Functional antibodies targeting IsaA of Staphylococcus aureus augment host immune response and open new perspectives for antibacterial therapy.

2.50
Hdl Handle:
http://hdl.handle.net/10033/136089
Title:
Functional antibodies targeting IsaA of Staphylococcus aureus augment host immune response and open new perspectives for antibacterial therapy.
Authors:
Lorenz, Udo; Lorenz, Birgit; Schmitter, Tim; Streker, Karin; Erck, Christian; Wehland, Jürgen; Nickel, Joachim; Zimmermann, Bastian; Ohlsen, Knut
Abstract:
Staphylococcus aureus is the most common cause of nosocomial infections. 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 S. aureus, 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 S. aureus strains tested, including hospital-acquired and community-acquired methicillin-resistant S. aureus strains. Therapeutic efficacy in vivo 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. Ex vivo, 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 S. aureus infections.
Affiliation:
Department of General, Visceral, Vascular and Paediatric Surgery, University Clinic of Würzburg, Wuerzburg, Germany. u.lorenz@mail.uni-wuerzburg.de
Citation:
Functional antibodies targeting IsaA of Staphylococcus aureus augment host immune response and open new perspectives for antibacterial therapy. 2011, 55 (1):165-73 Antimicrob. Agents Chemother.
Journal:
Antimicrobial agents and chemotherapy
Issue Date:
Jan-2011
URI:
http://hdl.handle.net/10033/136089
DOI:
10.1128/AAC.01144-10
PubMed ID:
20956605
Type:
Article
Language:
en
ISSN:
1098-6596
Appears in Collections:
publications of the research group cellular proteom research (CPRO)

Full metadata record

DC FieldValue Language
dc.contributor.authorLorenz, Udoen
dc.contributor.authorLorenz, Birgiten
dc.contributor.authorSchmitter, Timen
dc.contributor.authorStreker, Karinen
dc.contributor.authorErck, Christianen
dc.contributor.authorWehland, Jürgenen
dc.contributor.authorNickel, Joachimen
dc.contributor.authorZimmermann, Bastianen
dc.contributor.authorOhlsen, Knuten
dc.date.accessioned2011-07-14T09:21:23Z-
dc.date.available2011-07-14T09:21:23Z-
dc.date.issued2011-01-
dc.identifier.citationFunctional antibodies targeting IsaA of Staphylococcus aureus augment host immune response and open new perspectives for antibacterial therapy. 2011, 55 (1):165-73 Antimicrob. Agents Chemother.en
dc.identifier.issn1098-6596-
dc.identifier.pmid20956605-
dc.identifier.doi10.1128/AAC.01144-10-
dc.identifier.urihttp://hdl.handle.net/10033/136089-
dc.description.abstractStaphylococcus aureus is the most common cause of nosocomial infections. 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 S. aureus, 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 S. aureus strains tested, including hospital-acquired and community-acquired methicillin-resistant S. aureus strains. Therapeutic efficacy in vivo 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. Ex vivo, 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 S. aureus infections.en
dc.language.isoenen
dc.subject.meshAnimalsen
dc.subject.meshAntibodies, Bacterialen
dc.subject.meshAntigens, Bacterialen
dc.subject.meshFemaleen
dc.subject.meshFluorescent Antibody Technique, Indirecten
dc.subject.meshMaleen
dc.subject.meshMiceen
dc.subject.meshSepsisen
dc.subject.meshStaphylococcal Infectionsen
dc.subject.meshStaphylococcus aureusen
dc.titleFunctional antibodies targeting IsaA of Staphylococcus aureus augment host immune response and open new perspectives for antibacterial therapy.en
dc.typeArticleen
dc.contributor.departmentDepartment of General, Visceral, Vascular and Paediatric Surgery, University Clinic of Würzburg, Wuerzburg, Germany. u.lorenz@mail.uni-wuerzburg.deen
dc.identifier.journalAntimicrobial agents and chemotherapyen

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