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鉴定人体病原体洋葱伯克霍尔德氏菌的多功能三聚体自转运蛋白 BCAM0224。

Characterization of BCAM0224, a multifunctional trimeric autotransporter from the human pathogen Burkholderia cenocepacia.

机构信息

IBB-Institute for Biotechnology and Bioengineering, Instituto Superior Técnico, Lisbon, Portugal.

出版信息

J Bacteriol. 2014 Jun;196(11):1968-79. doi: 10.1128/JB.00061-14. Epub 2014 Mar 21.

Abstract

Members of the trimeric autotransporter adhesin (TAA) family play a crucial role in adhesion of Gram-negative pathogens to host cells. Moreover, these proteins are multifunctional virulence factors involved in several other biological traits, including invasion into host cells and evasion of the host immune system. In cystic fibrosis epidemic Burkholderia cenocepacia strain J2315, we identified a unique TAA (BCAM0224)-encoding gene, previously described as being implicated in virulence. Here, we characterized this multifunctional protein, trying to establish its role in B. cenocepacia pathogenicity. We show that BCAM0224 occurs on the bacterial surface and adopts a trimeric conformation. Furthermore, we demonstrated that BCAM0224 is needed for earlier stages of biofilm formation and is required for swarming motility. In addition, BCAM0224 plays an important role in evasion of the human innate immune system, providing resistance against the bactericidal activity of serum via the complement classical pathway. Finally, BCAM0224 mediates bacterial adhesion to and invasion of cultured human bronchial epithelial cells. Together, these data reveal the high versatility of the BCAM0224 protein as a virulence factor in the pathogenic bacterium B. cenocepacia.

摘要

三聚体自转运黏附素(TAA)家族的成员在革兰氏阴性病原体与宿主细胞黏附中起着至关重要的作用。此外,这些蛋白是多功能毒力因子,参与多种其他生物学特性,包括入侵宿主细胞和逃避宿主免疫系统。在囊性纤维化流行的伯克霍尔德氏菌中,我们鉴定了一个独特的 TAA(BCAM0224)编码基因,该基因先前被描述为与毒力有关。在这里,我们对这种多功能蛋白进行了表征,试图确定其在伯克霍尔德氏菌致病性中的作用。我们表明,BCAM0224 存在于细菌表面并采用三聚体构象。此外,我们证明 BCAM0224 是生物膜形成早期所必需的,并且是群集运动所必需的。此外,BCAM0224 在逃避人体先天免疫系统方面发挥着重要作用,通过补体经典途径提供对血清杀菌活性的抗性。最后,BCAM0224 介导细菌对培养的人支气管上皮细胞的黏附和入侵。总之,这些数据揭示了 BCAM0224 蛋白作为致病性细菌伯克霍尔德氏菌的毒力因子的高度多功能性。

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