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首页> 外文期刊>Infection and immunity >Molecular Basis for Preferential Protective Efficacy of Antibodies Directed to the Poorly Acetylated Form of Staphylococcal Poly-N-Acetyl-β-(1-6)-Glucosamine
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Molecular Basis for Preferential Protective Efficacy of Antibodies Directed to the Poorly Acetylated Form of Staphylococcal Poly-N-Acetyl-β-(1-6)-Glucosamine

机译：针对葡萄球菌聚-N-乙酰基-β-（1-6）-葡萄糖胺的不良乙酰化形式的抗体的优先保护功效的分子基础

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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.
机译：聚- N -乙酰氨基葡萄糖（PNAG）是一种葡萄球菌表面多糖，可影响生物膜的形成，目前也正在研究其疫苗潜力。与仅与高水平（> 70％）乙酸酯结合的PNAG抗体相比，与低水平（<15％）或高（> 90％）乙酸酯结合的PNAG抗体在调理和保护活性方面优越。 PNAG是由细胞内粘附素（ica）基因（ADAD）编码的四种蛋白质合成的。在表皮葡萄球菌中， icaB 编码PNAG表面保留和最佳生物膜形成所需的脱乙酰基酶。在这项研究中，我们证实了 icaB 在金黄色葡萄球菌中的作用相似，并发现了 S的 icaB 突变体。 aureus 的表面相关PNAG表达显着降低，对非依赖抗体的调理光杀死高度敏感，而抗脱乙酰基PNAG（dPNAG）产生的抗体无法增强这种作用，并且在鼠菌血症模型中的生存​​能力降低。相比之下，过表达 icaB 的菌株主要产生与表面相关的PNAG，对带有dPNAG抗体的调理吞噬细胞更敏感，并且在鼠菌血症模型中存活率提高。高度乙酰化的分泌型PNAG在阻止人单克隆抗体（mAb）对天然PNAG介导的调理杀伤方面比在阻止人mAb对dPNAG介导的杀伤方面更有效，后者本身就是更有效的调理素。 dPNAG在 S表面的保留。金黄色葡萄球菌是提高菌血症存活率的关键，并且提供了分子机制来解释抗dPNAG抗体的优越的调理作用和保护活性。

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