ArticleAntimicrobial agents and chemotherapy2011
Functional antibodies targeting IsaA of Staphylococcus aureus augment host immune response and open new perspectives for antibacterial therapy.
Article in Antimicrobial agents and chemotherapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 60 citations in OpenAlex.
- Safety, Tolerability, and Pharmacokinetics of MEDI4893, an Investigational, Extended-Half-Life, Anti-Staphylococcus aureus Alpha-Toxin Human Monoclonal Antibody, in Healthy Adults.Antimicrobial agents and chemotherapy · 2017Trial
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- Exploring the inhibition of the soluble lytic transglycosylase Cj0843c of Campylobacter jejuni via targeting different sites with different scaffolds.Protein science : a publication of the Protein Society · 2023Article
- Radiometal chelators for infection diagnostics.Frontiers in nuclear medicine · 2023Article
- Staphylococcus aureus cell wall maintenance - the multifaceted roles of peptidoglycan hydrolases in bacterial growth, fitness, and virulence.FEMS microbiology reviews · 2022Review
- Impact ofMicroorganisms · 2022Article
- Exoproteomic profiling uncovers critical determinants for virulence of livestock-associated and human-originatedVirulence · 2020Article
- AViruses · 2020Article
- Antibody-recruiting protein-catalyzed capture agents to combat antibiotic-resistant bacteria.Chemical science · 2020Article
- Roles of lytic transglycosylases in biofilm formation and β-lactam resistance in methicillin-resistantAntimicrobial agents and chemotherapy · 2019Article
- Exoproteome Heterogeneity among Closely Related Staphylococcus aureus t437 Isolates and Possible Implications for Virulence.Journal of proteome research · 2019Article
- Towards clinical application of non-invasive imaging to detect bacterial infections.Virulence · 2018Article
- Immunoproteomics to identify Staphylococcus aureus antigens expressed in bovine milk during mastitis.Journal of dairy science · 2018Article
- Human antibody responses against non-covalently cell wall-bound Staphylococcus aureus proteins.Scientific reports · 2018Article
- Humoral immune consequences of Staphylococcus aureus ST239-associated bacteremia.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2018Article
- A human monoclonal antibody that specifically binds and inhibits the staphylococcal complement inhibitor protein SCIN.Virulence · 2018Article
- Article
- Flotillin scaffold activity contributes to type VII secretion system assembly in Staphylococcus aureus.PLoS pathogens · 2017Article
- Differential epitope recognition in the immunodominant staphylococcal antigen A of Staphylococcus aureus by mouse versus human IgG antibodies.Scientific reports · 2017Article
- Advances in antibiotic therapy in the critically ill.Critical care (London, England) · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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.
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