Role of AmiA in the morphological transition of Helicobacter pylori and in immune escape.
Role of AmiA in the morphological transition of Helicobacter pylori and in immune escape.
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DOI：
10.1371/journal.ppat.0020097
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发表时间：
2006-09
期刊：
影响因子：
6.7
通讯作者：
Boneca IG
中科院分区：
文献类型：
--
作者：
Chaput C;Ecobichon C;Cayet N;Girardin SE;Werts C;Guadagnini S;Prévost MC;Mengin-Lecreulx D;Labigne A;Boneca IG
人类胃病原体幽门螺杆菌是导致消化性溃疡和肿瘤的原因。无论是在体外还是在人胃中，它都可以以两种形式存在，即杆状和球状形式。这两种形式之间的形态过渡的分子机制和球菌的作用仍然在很大程度上未知。肽聚糖（PG）层是细菌细胞形状的主要决定因素，因此我们研究了H。pylori PG结构在形态转变过程中的变化。该转变与N-乙酰基-D-葡糖胺基-β（1，4）-N-乙酰基胞壁酰-L-Ala-D-Glu（GM-二肽）基序的积累相关。我们研究了负责GM-二肽基序积累的分子机制，并研究了各种假定的PG水解酶在这一过程中的作用。有趣的是，编码推定的PG水解酶的amiA基因中具有突变的突变菌株在积累GM-二肽基序和转化成球形体中受损。我们研究了形态转变和PG修饰在H.幽门。PG修饰和H. pylori感染的同时，上皮细胞中Nod 1逃避检测，NF-κB活化缺失。因此，球孢子不能诱导AGS胃上皮细胞分泌IL-8。据我们所知，amiA是发现的第一个遗传决定子，是这种形态转变为球形体所必需的，因此有助于调节宿主反应并参与H.幽门感染 幽门螺杆菌是引起胃溃疡和胃癌等胃疾病的人类病原体。尽管宿主的免疫反应很强，但H。幽门螺杆菌能够在其人类宿主中持续数十年。H.在活组织检查中发现幽门以两种不同的形式存在，螺旋杆形式和球形形式。Chaput等人研究了导致H转变的分子机制。幽门螺杆菌从螺旋杆状生物体转变为球形生物体。形态转变伴随着细菌细胞壁肽聚糖的修饰。作者已经确定AmiA蛋白对于细胞壁肽聚糖的这种形态转变和修饰是必不可少的。此外，作者还表明，细胞壁的修饰和形态学的转变使这些球形体逃避了免疫系统的检测，因此可能参与了H.幽门螺杆菌感染在其人类宿主的一生中。
The human gastric pathogen Helicobacter pylori is responsible for peptic ulcers and neoplasia. Both in vitro and in the human stomach it can be found in two forms, the bacillary and coccoid forms. The molecular mechanisms of the morphological transition between these two forms and the role of coccoids remain largely unknown. The peptidoglycan (PG) layer is a major determinant of bacterial cell shape, and therefore we studied H. pylori PG structure during the morphological transition. The transition correlated with an accumulation of the N-acetyl-D-glucosaminyl-β(1,4)-N-acetylmuramyl-L-Ala–D-Glu (GM-dipeptide) motif. We investigated the molecular mechanisms responsible for the GM-dipeptide motif accumulation, and studied the role of various putative PG hydrolases in this process. Interestingly, a mutant strain with a mutation in the amiA gene, encoding a putative PG hydrolase, was impaired in accumulating the GM-dipeptide motif and transforming into coccoids. We investigated the role of the morphological transition and the PG modification in the biology of H. pylori. PG modification and transformation of H. pylori was accompanied by an escape from detection by human Nod1 and the absence of NF-κB activation in epithelial cells. Accordingly, coccoids were unable to induce IL-8 secretion by AGS gastric epithelial cells. amiA is, to our knowledge, the first genetic determinant discovered to be required for this morphological transition into the coccoid forms, and therefore contributes to modulation of the host response and participates in the chronicity of H. pylori infection. Helicobacter pylori is a human pathogen responsible for gastric diseases such as ulcers and gastric cancers. Despite the host's vigorous immune response, H. pylori is capable of persisting for decades in its human host. H. pylori is found in biopsies in two distinct forms, a spiral rod form and a coccoid form. Chaput et al. investigated the molecular mechanisms leading to the transition of H. pylori from a spiral rod–shaped organism to a coccoid organism. The morphological transition is accompanied by modifications of the bacterial cell wall peptidoglycan. The authors have identified the AmiA protein as essential for this morphological transition and modification of the cell wall peptidoglycan. Additionally, the authors show that the cell wall modifications and morphological transition allow these coccoid forms to escape detection by the immune system and therefore could participate in the persistence of H. pylori infection during the lifetime of its human host.
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影响因子：
4.8
作者：
Gutierrez, O;Pipaon, C;Fernandez-Luna, JL
通讯作者：
Fernandez-Luna, JL
DOI：
10.1046/j.0014-2956.2001.02524.x
发表时间：
2001-11-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Dementin, S;Bouhss, A;Blanot, D
通讯作者：
Blanot, D
影响因子：
4.4
作者：
Adams, BL;Bates, TC;Oliver, JD
通讯作者：
Oliver, JD
影响因子：
--
作者：
Aleljung, P;Nilsson, HO;Wadstrom, T
通讯作者：
Wadstrom, T
影响因子：
24.5
作者：
Hidaka, E;Ota, H;Katsuyama, T
通讯作者：
Katsuyama, T