Department of Medicine, Vanderbilt University, School of Medicine, Nashville, Tennessee, USA.
mBio. 2013 Apr 9;4(2):e00613-12. doi: 10.1128/mBio.00613-12.
Helicobacter pylori contains four genes that are predicted to encode proteins secreted by the autotransporter (type V) pathway. One of these, the pore-forming toxin VacA, has been studied in great detail, but thus far there has been very little investigation of three VacA-like proteins. We show here that all three VacA-like proteins are >250 kDa in mass and localized on the surface of H. pylori. The expression of the three vacA-like genes is upregulated during H. pylori colonization of the mouse stomach compared to H. pylori growth in vitro, and a wild-type H. pylori strain outcompeted each of the three corresponding isogenic mutant strains in its ability to colonize the mouse stomach. One of the VacA-like proteins localizes to a sheath that overlies the flagellar filament and bulb, and therefore, we designate it FaaA (flagella-associated autotransporter A). In comparison to a wild-type H. pylori strain, an isogenic faaA mutant strain exhibits decreased motility, decreased flagellar stability, and an increased proportion of flagella in a nonpolar site. The flagellar localization of FaaA differs markedly from the localization of other known autotransporters, and the current results reveal an important role of FaaA in flagellar localization and motility.
The pathogenesis of most bacterial infections is dependent on the actions of secreted proteins, and proteins secreted by the autotransporter pathway constitute the largest family of secreted proteins in pathogenic Gram-negative bacteria. In this study, we analyzed three autotransporter proteins (VacA-like proteins) produced by Helicobacter pylori, a Gram-negative bacterium that colonizes the human stomach and contributes to the pathogenesis of gastric cancer and peptic ulcer disease. We demonstrate that these three proteins each enhance the capacity of H. pylori to colonize the stomach. Unexpectedly, one of these proteins (FaaA) is localized to a sheath that overlies H. pylori flagella. The absence of FaaA results in decreased H. pylori motility as well as a reduction in flagellar stability and a change in flagellar localization. The atypical localization of FaaA reflects a specialized function of this autotransporter designed to optimize H. pylori colonization of the gastric niche.
幽门螺杆菌含有四个基因，这些基因被预测编码通过自转运体（V 型）途径分泌的蛋白质。其中一种，形成孔的毒素 VacA，已经进行了详细的研究，但到目前为止，对三种 VacA 样蛋白的研究很少。我们在这里表明，所有三种 VacA 样蛋白的分子量都超过 250 kDa，并且定位于幽门螺杆菌的表面。与幽门螺杆菌在体外生长相比，三种 vacA 样基因在幽门螺杆菌定植于小鼠胃时的表达上调，并且野生型幽门螺杆菌菌株在定植于小鼠胃的能力方面胜过三种相应的同基因突变菌株。一种 VacA 样蛋白定位于覆盖鞭毛丝和鞭毛球的鞘上，因此，我们将其命名为 FaaA（鞭毛相关自转运体 A）。与野生型幽门螺杆菌菌株相比，同基因的 faaA 突变菌株表现出运动性降低、鞭毛稳定性降低以及非极性部位的鞭毛比例增加。FaaA 的鞭毛定位与其他已知的自转运体明显不同，并且当前的结果揭示了 FaaA 在鞭毛定位和运动中的重要作用。
大多数细菌感染的发病机制依赖于分泌蛋白的作用，并且自转运体途径分泌的蛋白构成了致病性革兰氏阴性菌中最大的分泌蛋白家族。在这项研究中，我们分析了幽门螺杆菌产生的三种自转运体蛋白（VacA 样蛋白），幽门螺杆菌是一种定植于人类胃并导致胃癌和消化性溃疡病发病的革兰氏阴性菌。我们证明这三种蛋白都增强了幽门螺杆菌定植胃的能力。出乎意料的是，这些蛋白之一（FaaA）定位于覆盖幽门螺杆菌鞭毛的鞘上。FaaA 的缺失导致幽门螺杆菌运动性降低，以及鞭毛稳定性降低和鞭毛定位改变。FaaA 的非典型定位反映了这种自转运体的特殊功能，旨在优化幽门螺杆菌对胃生态位的定植。
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