Institute for Medical Microbiology and Infection Control, University Hospital, Goethe University, Frankfurt, Germany.
Department of Biotechnology, Graduate School of Engineering, Nagoya University, Nagoya, Japan.
Virulence. 2019 Dec;10(1):68-81. doi: 10.1080/21505594.2018.1558693.
is a Gram-negative pathogen that causes a multitude of nosocomial infections. The trimeric autotransporter adhesin (Ata) belongs to the superfamily of trimeric autotransporter adhesins which are important virulence factors in many Gram-negative species. Phylogenetic profiling revealed that is present in 78% of all sequenced isolates but only in 2% of the closely related species and . Employing a markerless deletion mutant of ATCC 19606 we show that adhesion to and invasion into human endothelial and epithelial cells depend on Ata. Infection of primary human umbilical cord vein endothelial cells (HUVECs) with led to the secretion of interleukin (IL)-6 and IL-8 in a time- and Ata-dependent manner. Furthermore, infection of HUVECs by WT was associated with higher rates of apoptosis via activation of caspases-3 and caspase-7, but not necrosis, in comparison to ∆. Ata deletion mutants were furthermore attenuated in their ability to kill larvae of and to survive in larvae when injected at sublethal doses. This indicates that Ata is an important multifunctional virulence factor in that mediates adhesion and invasion, induces apoptosis and contributes to pathogenicity .
是一种革兰氏阴性病原体，可引起多种医院获得性感染。三聚体自转运黏附素（Ata）属于三聚体自转运黏附素超家族，该超家族是许多革兰氏阴性物种的重要毒力因子。系统发育分析显示，在所有测序的 分离株中， 存在于 78%，而在密切相关的 和 物种中仅存在于 2%。我们利用 ATCC 19606 的无标记缺失突变体证明，黏附和侵袭人血管内皮细胞和上皮细胞依赖于 Ata。与 ∆ 相比，用野生型 感染原代人脐静脉内皮细胞（HUVEC）可通过依赖于 Ata 的时间和方式导致白细胞介素（IL）-6 和 IL-8 的分泌。此外，与 ∆ 相比，WT 感染 HUVEC 可通过激活 caspase-3 和 caspase-7 导致更高的细胞凋亡率，而不是坏死。与野生型相比，Ata 缺失突变体在杀死 幼虫和在亚致死剂量注射时在幼虫中存活的能力减弱。这表明 Ata 是 中的一种重要多功能毒力因子，可介导黏附和侵袭，诱导细胞凋亡并有助于致病性。
