Staphylococcus aureus keratinocyte invasion is dependent upon multiple high-affinity fibronectin-binding repeats within FnBPA.
Staphylococcus aureus keratinocyte invasion is dependent upon multiple high-affinity fibronectin-binding repeats within FnBPA.
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DOI：
10.1371/journal.pone.0018899
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发表时间：
2011-04-22
期刊：
影响因子：
3.7
通讯作者：
Massey RC
中科院分区：
文献类型：
--
作者：
Edwards AM;Potter U;Meenan NA;Potts JR;Massey RC
金黄色葡萄球菌（Staphylococcus aureus）是一种常见的皮肤和软组织感染病原体，可发展为严重的侵袭性疾病。这种细菌使用其纤连蛋白结合蛋白（FnBP）侵入宿主细胞，并且已经假设这提供了一个受保护的小生境，免受宿主抗微生物防御的影响，允许进入更深的组织，并为持续或复发的感染提供了储库。FnBP含有多个串联的纤连蛋白结合重复序列（FnBR），其以不同的亲和力结合纤连蛋白，但尚不清楚这种构型的选择。由于定植和皮肤感染都依赖于S.我们假设这可能选择FnBP功能，从而选择FnBR区域的组成。初步实验表明，S.金黄色葡萄球菌与角质形成细胞的附着是快速的，但不需要FnBR。相比之下，角质形成细胞的侵袭依赖于FnBR区域，并通过与内皮细胞所描述的细胞过程相似的细胞过程发生。尽管如此，角质形成细胞侵袭相对低效，并且似乎包括滞后期，最可能是由于α5β1整联蛋白的非常弱的表达。FnBR区域的作用的分子解剖显示，角质形成细胞的有效侵袭依赖于至少三个高亲和力（但不是低亲和力）FnBR的存在。单个高亲和力重复序列或三个低亲和力重复序列的过表达促进了入侵，但没有达到与S相同的水平。金黄色葡萄球菌表达含有三个高亲和力重复的FnBPA变体。总之，S.金黄色葡萄球菌需要FnBPA内的多个高亲和力FnBR，并且考虑到这些细胞类型与金黄色葡萄球菌之间相互作用的重要性。金黄色葡萄球菌的定植和感染，可能提供了选择性压力的多个结合重复内FnBPA。
Staphylococcus aureus is a commensal organism and a frequent cause of skin and soft tissue infections, which can progress to serious invasive disease. This bacterium uses its fibronectin binding proteins (FnBPs) to invade host cells and it has been hypothesised that this provides a protected niche from host antimicrobial defences, allows access to deeper tissues and provides a reservoir for persistent or recurring infections. FnBPs contain multiple tandem fibronectin-binding repeats (FnBRs) which bind fibronectin with varying affinity but it is unclear what selects for this configuration. Since both colonisation and skin infection are dependent upon the interaction of S. aureus with keratinocytes we hypothesised that this might select for FnBP function and thus composition of the FnBR region. Initial experiments revealed that S. aureus attachment to keratinocytes is rapid but does not require FnBRs. By contrast, invasion of keratinocytes was dependent upon the FnBR region and occurred via similar cellular processes to those described for endothelial cells. Despite this, keratinocyte invasion was relatively inefficient and appeared to include a lag phase, most likely due to very weak expression of α5β1 integrins. Molecular dissection of the role of the FnBR region revealed that efficient invasion of keratinocytes was dependent on the presence of at least three high-affinity (but not low-affinity) FnBRs. Over-expression of a single high-affinity or three low-affinity repeats promoted invasion but not to the same levels as S. aureus expressing an FnBPA variant containing three high-affinity repeats. In summary, invasion of keratinocytes by S. aureus requires multiple high-affinity FnBRs within FnBPA, and given the importance of the interaction between these cell types and S. aureus for both colonisation and infection, may have provided the selective pressure for the multiple binding repeats within FnBPA.
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