Utilize este identificador para referenciar este registo:
https://hdl.handle.net/1822/6678
Título: | Molecular basis for preferential protective efficacy of antibodies directed to the poorly acetylated form of staphylococcal poly-N-acetyl-β-(1-6)-glucosamine |
Autor(es): | Cerca, Nuno Jefferson, Kimberly K. Maira-Litrán, Tomas Pier, Danielle B. Kelly-Quintos, Casie Goldmann, Donald A. Azeredo, Joana Pier, Gerald B. |
Data: | Jul-2007 |
Editora: | American Society for Microbiology (ASM) |
Revista: | Infection and Immunity |
Citação: | "Infection and Immunity". ISSN 0019-9567. 75:7 (July 2007) 3406-3413. |
Resumo(s): | Poly-N-acetyl-glucosamine (PNAG) is a staphylococcal surface polysaccharide influencing biofilm formation that is also under investigation for its vaccine potential. Antibodies that bind to PNAG with either low (<15%) or high (>90%) levels of acetate are superior at opsonic and protective activity compared with antibodies that bind to PNAG with only high levels (>70%) of acetate. PNAG is synthesized by four proteins encoded within the intercellular adhesin (ica) locus icaADBC. In Staphylococcus epidermidis, icaB encodes a deacetylase needed for the surface retention of PNAG and optimal biofilm formation. In this study, we confirmed that icaB plays a similar role in Staphylococcus aureus and found that an icaB mutant of S. aureus expressed significantly less surface-associated PNAG, was highly susceptible to antibody-independent opsonic killing that could not be enhanced with antibody raised against deacetylated PNAG (dPNAG), and had reduced survival capacity in a murine model of bacteremia. In contrast, an icaB-overexpressing strain produced primarily surface-associated PNAG, was more susceptible to opsonophagocytosis with antibody to dPNAG, and had increased survival in a murine bacteremia model. The highly acetylated secreted PNAG was more effective at blocking opsonic killing mediated by a human monoclonal antibody (mAb) to native PNAG than it was at blocking killing mediated by a human mAb to dPNAG, which by itself was a more effective opsonin. Retention of dPNAG on the surface of S. aureus is key to increased survival during bacteremia and also provides a molecular mechanism explaining the superior opsonic and protective activity of antibody to dPNAG. |
Tipo: | Artigo |
URI: | https://hdl.handle.net/1822/6678 |
DOI: | 10.1128/IAI.00078-07 |
ISSN: | 0019-9567 |
Arbitragem científica: | yes |
Acesso: | Acesso aberto |
Aparece nas coleções: | CEB - Publicações em Revistas/Séries Internacionais / Publications in International Journals/Series |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
---|---|---|---|---|
Cerca_I&I-07-07[2].pdf | 248,61 kB | Adobe PDF | Ver/Abrir |