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Evolving serodiagnostics by rationally designed peptide arrays: the Burkholderia paradigm in Cystic Fibrosis

机译:通过合理设计的肽阵列进行的血清学诊断:囊性纤维化的伯克霍尔德病范式

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摘要

Efficient diagnosis of emerging and novel bacterial infections is fundamental to guide decisions on therapeutic treatments. Here, we engineered a novel rational strategy to design peptide microarray platforms, which combines structural and genomic analyses to predict the binding interfaces between diverse protein antigens and antibodies against Burkholderia cepacia complex infections present in the sera of Cystic Fibrosis (CF) patients. The predicted binding interfaces on the antigens are synthesized in the form of isolated peptides and chemically optimized for controlled orientation on the surface. Our platform displays multiple Burkholderia-related epitopes and is shown to diagnose infected individuals even in presence of superinfections caused by other prevalent CF pathogens, with limited cost and time requirements. Moreover, our data point out that the specific patterns determined by combined probe responses might provide a characterization of Burkholderia infections even at the subtype level (genomovars). The method is general and immediately applicable to other bacteria.
机译:有效诊断新兴和新型细菌感染是指导治疗决策的基础。在这里,我们设计了一种新颖的合理策略来设计肽微阵列平台,该平台结合了结构和基因组分析,以预测各种蛋白质抗原与针对囊性纤维化(CF)患者血清中存在的洋葱伯克霍尔德菌菌感染的抗体之间的结合界面。抗原上的预测结合界面以分离肽的形式合成,并针对表面上的受控方向进行了化学优化。我们的平台展示了多个与伯克霍尔德菌相关的抗原决定簇,并被证明即使在由其他流行CF病原体引起的超级感染的情况下,也可以诊断受感染的个人,且费用和时间要求有限。此外,我们的数据指出,由组合探针反应确定的特定模式甚至可以在亚型水平(基因型)上提供伯克霍尔德氏菌感染的特征。该方法是通用的,可立即应用于其他细菌。

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