Helicobacter pylori usurps cell polarity to turn the cell surface into a replicative niche.
Helicobacter pylori usurps cell polarity to turn the cell surface into a replicative niche.
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DOI：
10.1371/journal.ppat.1000407
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发表时间：
2009-05
期刊：
影响因子：
6.7
通讯作者：
Amieva MR
中科院分区：
文献类型：
--
作者：
Tan S;Tompkins LS;Amieva MR
幽门螺杆菌（Helicobacter pylori，Hp）与胃上皮细胞表面密切相互作用，并以接触依赖的方式将毒力因子CagA转运到宿主细胞中。为了研究Hp如何从与细胞表面的相互作用中受益，我们开发了活细胞显微镜方法来跟踪细胞表面上单个细菌的命运，并发现Hp能够直接在细胞间连接处复制和形成小菌落。在极化上皮上，Hp能够在不支持自由游动细菌生长的条件下直接在顶端细胞表面上生长。相反，CagA递送中的突变体在顶端细胞表面的定殖中是有缺陷的。由于野生型Hp在共感染时不能挽救CagA缺陷突变体的生长缺陷，因此Hp以高度局部化的方式扰乱极化上皮。CagA破坏宿主细胞极性的能力是使Hp能够在顶端细胞表面定植的关键因素，因为非典型蛋白激酶C/Par 1b极性途径的破坏导致顶端感染期间突变体生长缺陷的拯救，并且CagA缺陷突变体能够在获得基底外侧细胞表面时在极化上皮上定植。我们的研究建立了细胞表面作为一个复制的小生境和CagA的重要性及其对宿主细胞极性为此目的的影响。 幽门螺杆菌（Hp）是一种慢性感染人类胃的细菌，在某些情况下会导致胃癌和溃疡等疾病。这种细菌生活在靠近上皮衬里的地方，可以直接粘附在宿主细胞膜上并释放毒素。我们利用活细胞成像和极化上皮细胞的细胞培养模型来解决Hp附着在细胞表面的原因。我们发现，即使在自由游动的细菌被迅速杀死的情况下，Hp也能够在上皮细胞表面生长。与这种在细胞表面定殖的能力有关的一种机制是毒力因子CagA，它由细菌直接注入宿主细胞。我们发现，CagA的能力，扰乱细胞的极性是重要的有效的生存和生长的Hp的顶端表面的宿主细胞。我们的研究建立了细胞表面作为细菌生长的生态位，并阐明了CagA对细菌的作用。
Helicobacter pylori (Hp) intimately interacts with the gastric epithelial surface and translocates the virulence factor CagA into host cells in a contact-dependent manner. To study how Hp benefits from interacting with the cell surface, we developed live-cell microscopy methods to follow the fate of individual bacteria on the cell surface and find that Hp is able to replicate and form microcolonies directly over the intercellular junctions. On polarized epithelia, Hp is able to grow directly on the apical cell surface in conditions that do not support the growth of free-swimming bacteria. In contrast, mutants in CagA delivery are defective in colonization of the apical cell surface. Hp perturbs the polarized epithelium in a highly localized manner, since wild-type Hp does not rescue the growth defect of the CagA-deficient mutants upon co-infection. CagA's ability to disrupt host cell polarity is a key factor in enabling colonization of the apical cell surface by Hp, as disruption of the atypical protein kinase C/Par1b polarity pathway leads to rescue of the mutant growth defect during apical infection, and CagA-deficient mutants are able to colonize the polarized epithelium when given access to the basolateral cell surface. Our study establishes the cell surface as a replicative niche and the importance of CagA and its effects on host cell polarity for this purpose. Helicobacter pylori (Hp) is a bacterium that chronically infects the human stomach, in some cases leading to diseases such as stomach cancer and ulcers. The bacteria live in close proximity to the epithelial lining and can adhere directly to the host cell membrane and deliver toxins. We utilized live-cell imaging and a cell culture model of polarized epithelial cells to address why Hp attaches to the cell surface. We discovered that Hp is able to grow on the surface of epithelial cells, even in conditions where the free-swimming bacteria are rapidly killed. One mechanism involved in this ability to colonize the cell surface is the virulence factor CagA, which is injected directly into host cells by the bacteria. We found that CagA's ability to perturb cell polarity is important for the efficient survival and growth of Hp on the apical surface of the host cell. Our study establishes the cell surface as a niche for bacterial growth and elucidates a role of CagA for the bacterium.
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影响因子：
6.7
作者：
Chaput C;Ecobichon C;Cayet N;Girardin SE;Werts C;Guadagnini S;Prévost MC;Mengin-Lecreulx D;Labigne A;Boneca IG
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