Infection of human mucosal tissue by Pseudomonas aeruginosa requires sequential and mutually dependent virulence factors and a novel pilus-associated adhesin.
Infection of human mucosal tissue by Pseudomonas aeruginosa requires sequential and mutually dependent virulence factors and a novel pilus-associated adhesin.
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DOI：
10.1111/j.1462-5822.2010.01461.x
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发表时间：
2010-08
影响因子：
3.4
通讯作者：
Wolfgang MC
中科院分区：
文献类型：
--
作者：
Heiniger RW;Winther-Larsen HC;Pickles RJ;Koomey M;Wolfgang MC
组织损伤使人类容易受到条件致病菌铜绿假单胞菌的传播感染，从而危及生命。细菌对宿主组织的黏附是这一感染过程中至关重要的第一步。众所周知，铜绿假单胞菌与宿主细胞的附着涉及IV型菌毛(TFP)，TFP是一种可伸缩的表面纤维。附着的分子细节以及细菌粘附素和宿主受体的身份仍然存在争议。使用来自原生人类组织的粘膜上皮模型系统，我们证明了菌毛相关蛋白PilY1是细菌黏附所必需的。我们证实，铜绿假单胞菌优先结合到暴露的基底外侧宿主细胞表面，为受损组织的机会性感染提供了一个机械解释。此外，我们证明了完整宿主组织的入侵和暴发性感染需要多种细菌因素的协调和相互依赖的作用，包括菌毛纤维回缩和宿主细胞中毒系统，称为III型分泌。我们的发现为病原体与其宿主之间的复杂相互作用提供了新的和重要的见解，并提供了令人信服的证据，证明PilY1是人类组织的主要铜绿假单胞菌粘附素，它特异性地识别定位或丰富在基底外侧上皮细胞表面的宿主受体。
Tissue damage predisposes humans to life-threatening disseminating infection by the opportunistic pathogen Pseudomonas aeruginosa. Bacterial adherence to host tissue is a critical first step in this infection process. It is well established that P. aeruginosa attachment to host cells involves type IV pili (TFP), which are retractile surface fibers. The molecular details of attachment and the identity of the bacterial adhesin and host receptor remain controversial. Using a mucosal epithelium model system derived from primary human tissue, we show that the pilus-associated protein PilY1 is required for bacterial adherence. We establish that P. aeruginosa preferentially binds to exposed basolateral host cell surfaces, providing a mechanistic explanation for opportunistic infection of damaged tissue. Further, we demonstrate that invasion and fulminant infection of intact host tissue requires the coordinated and mutually dependent action of multiple bacterial factors, including pilus fiber retraction and the host cell intoxication system, termed type III secretion. Our findings offer new and important insights into the complex interactions between a pathogen and its human host and provide compelling evidence that PilY1 serves as the principal P. aeruginosa adhesin for human tissue and that it specifically recognizes a host receptor localized or enriched on basolateral epithelial cell surfaces.
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影响因子：
3.1
作者：
Bucior, Iwona;Mostov, Keith;Engel, Joanne N.
通讯作者：
Engel, Joanne N.
影响因子：
2.8
作者：
Chiang, Poney;Sampaleanu, Liliana M.;Burrows, Lori L.
通讯作者：
Burrows, Lori L.
DOI：
10.1073/pnas.0707581104
发表时间：
2007-10-02
影响因子：
11.1
作者：
Helaine, Sophie;Dyer, David H.;Forest, Katrina T.
通讯作者：
Forest, Katrina T.
影响因子：
3.4
作者：
Hyland, Romney M.;Sun, Jiangxiao;Armstrong, Glen D.
通讯作者：
Armstrong, Glen D.
影响因子：
3.2
作者：
Collins, RF;Davidsen, L;Tonjum, T
通讯作者：
Tonjum, T