School of Cellular & Molecular Medicine, University of Bristol, Bristol, United Kingdom.
PLoS One. 2012;7(9):e45452. doi: 10.1371/journal.pone.0045452. Epub 2012 Sep 25.
Moraxella catarrhalis (Mx) is a common cause of otitis media and exacerbation of chronic obstructive pulmonary disease, an increasing worldwide problem. Surface proteins UspA1 and UspA2 of Mx bind to a number of human receptors and may function in pathogenesis. Genetic recombination events in the pathogen can generate hybrid proteins termed UspA2H. However, whether certain key functions (e.g. UspA1-specific CEACAM binding) can be exchanged between these adhesin families remains unknown. In this study, we have shown that Mx can incorporate the UspA1 CEACAM1-binding region not only into rare UspA1 proteins devoid of CEACAM-binding ability, but also into UspA2 which normally lack this capacity. Further, a screen of Mx isolates revealed the presence of novel UspA2 Variant proteins (UspA2V) in ∼14% of the CEACAM-binding population. We demonstrate that the expression of UspA2/2V with the CEACAM-binding domain enable Mx to bind both to cell surface CEACAMs and to integrins, the latter via vitronectin. Such properties of UspA2/2V have not been reported to date. The studies demonstrate that the UspA family is much more heterogeneous than previously believed and illustrate the in vivo potential for exchange of functional regions between UspA proteins which could convey novel adhesive functions whilst enhancing immune evasion.
卡他莫拉菌（Mx）是中耳炎和慢性阻塞性肺疾病恶化的常见病因，这是一个在全球范围内日益严重的问题。Mx 的表面蛋白 UspA1 和 UspA2 与许多人类受体结合，可能在发病机制中发挥作用。病原体中的基因重组事件可产生称为 UspA2H 的混合蛋白。然而，某些关键功能（例如 UspA1 特异性 CEACAM 结合）是否可以在这些黏附家族之间交换尚不清楚。在这项研究中，我们表明 Mx 不仅可以将 UspA1 的 CEACAM1 结合区域整合到缺乏 CEACAM 结合能力的罕见 UspA1 蛋白中，还可以整合到通常缺乏这种能力的 UspA2 中。此外，对 Mx 分离株的筛选显示，在约 14%的 CEACAM 结合群体中存在新型 UspA2 变体蛋白（UspA2V）。我们证明，表达具有 CEACAM 结合结构域的 UspA2/2V 使 Mx 能够结合细胞表面的 CEACAMs 和整合素，后者通过 vitronectin。迄今为止，尚未报道 UspA2/2V 的这些特性。这些研究表明，UspA 家族比以前认为的更加多样化，并说明了 UspA 蛋白之间功能区域交换的体内潜力，这可能赋予新的黏附功能，同时增强免疫逃避。
