Coiled Coil Rich Proteins (Ccrp) Influence Molecular Pathogenicity of Helicobacter pylori
Coiled Coil Rich Proteins (Ccrp) Influence Molecular Pathogenicity of Helicobacter pylori
复制标题
卷曲螺旋丰富蛋白 (Ccrp) 影响幽门螺杆菌的分子致病性
作者：
S. Schätzle;M. Specht;Barbara Waidner
人类病原体幽门螺杆菌的致病性依赖于其适应恶劣环境和逃避宿主反应的能力。虽然我们对细菌细胞骨架的理解有了很大的进步，但我们对它对毒力的贡献的认识仍然存在重大差距。本研究探讨了富含卷曲螺旋蛋白（Ccrp）的细胞骨架元件对H.幽门。缺失任何一个ccrp都会导致主要致病因子尿素酶活性的强烈下降。我们进一步研究了他们的作用，使用体外共培养实验与人胃腺癌细胞系AGS模拟H。pylori -宿主细胞相互作用。有趣的是，在与任何ccrp缺失突变体共孵育后，宿主细胞仅显示出弱的“散射/蜂鸟”表型，其中宿主细胞从均匀的多边形形状转变为严重伸长的状态，其特征在于形成针状突起。此外，与ccrp 59突变体共孵育导致IV型分泌系统相关活性降低，例如IL-8产生和CagA易位/磷酸化。因此，除了它们在维持H.幽门螺杆菌Ccrp蛋白影响许多细胞过程，因此对这种人类病原体的毒力至关重要。
Pathogenicity of the human pathogen Helicobacter pylori relies on its capacity to adapt to a hostile environment and to escape the host response. Although there have been great advances in our understanding of the bacterial cytoskeleton, major gaps remain in our knowledge of its contribution to virulence. In this study we have explored the influence of coiled coil rich proteins (Ccrp) cytoskeletal elements on pathogenicity factors of H. pylori. Deletion of any of the ccrp resulted in a strongly decreased activity of the main pathogenicity factor urease. We further investigated their role using in vitro co-culture experiments with the human gastric adenocarcinoma cell line AGS modeling H. pylori - host cell interactions. Intriguingly, host cell showed only a weak “scattering/hummingbird” phenotype, in which host cells are transformed from a uniform polygonal shape into a severely elongated state characterized by the formation of needle-like projections, after co-incubation with any ccrp deletion mutant. Furthermore, co-incubation with the ccrp59 mutant resulted in reduced type IV secretion system associated activities, e.g. IL-8 production and CagA translocation/phosphorylation. Thus, in addition to their role in maintaining the helical cell shape of H. pylori Ccrp proteins influence many cellular processes and are thereby crucial for the virulence of this human pathogen.
登录
查看更多内容
DOI：
10.1073/pnas.96.25.14559
发表时间：
1999-12-07
影响因子：
11.1
作者：
Segal, ED;Cha, J;Tompkins, LS
通讯作者：
Tompkins, LS
影响因子：
1.9
作者：
MOBLEY, HLT;HU, LT;FOXALL, PA
通讯作者：
FOXALL, PA
影响因子：
3.5
作者：
HO, SN;HUNT, HD;PEASE, LR
通讯作者：
PEASE, LR
DOI：
10.1073/pnas.0409873102
发表时间：
2005-06-28
影响因子：
11.1
作者：
Brandt, S;Kwok, T;Backert, S
通讯作者：
Backert, S
影响因子：
6.7
作者：
Jiménez-Soto LF;Kutter S;Sewald X;Ertl C;Weiss E;Kapp U;Rohde M;Pirch T;Jung K;Retta SF;Terradot L;Fischer W;Haas R
通讯作者：
Haas R