Multiple peptidoglycan modification networks modulate Helicobacter pylori's cell shape, motility, and colonization potential.
Multiple peptidoglycan modification networks modulate Helicobacter pylori's cell shape, motility, and colonization potential.
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DOI：
10.1371/journal.ppat.1002603
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发表时间：
2012
期刊：
影响因子：
6.7
通讯作者：
Salama NR
中科院分区：
文献类型：
--
作者：
Sycuro LK;Wyckoff TJ;Biboy J;Born P;Pincus Z;Vollmer W;Salama NR
胃病原体幽门螺杆菌的螺旋细胞形状已被认为通过粘度依赖性的游泳速度的增强来提高毒力。然而，H.弯曲但缺乏螺旋扭转的幽门螺杆菌CSD 1突变体在粘性聚合物溶液中显示正常速度，并且它们在胃定殖中缺乏的原因仍然不清楚。新的棒状突变体的表征确定了Csd 4，肽聚糖（PG）三肽单体的DL-羧肽酶和Csd 5，一个假定的支架蛋白。形态学和生化研究表明，Csd 4三肽切割和Csd 1交联松弛修改PG球囊通过独立的网络，协调产生螺旋形状。csd 4突变体显示胃定植的衰减，但促炎细胞因子诱导没有变化，尽管PG球囊中Nod 1激动剂三肽的水平高出4倍。运动分析类似形状的突变体轴承PG修改不同的变化显示赤字与形状，但仅在凝胶状介质，而不是粘性的解决方案。由于胃粘液表现出粘弹性凝胶样的性质，我们的研究结果表明，增强的粘液屏障渗透的基础上赋予的健身优势H。pylori的特征形状幽门螺杆菌的唯一栖息地是人类的胃，在那里它可以促进胃溃疡和癌症。由聚合的胃粘蛋白组成的一层厚厚的胃粘液保护胃细胞免受鲁米那酸的侵害。胃粘蛋白在中性pH值下的粘弹性溶液到低pH值下的粘弹性凝胶状状态之间经历物理转变。缺乏螺旋扭曲的幽门螺杆菌突变体在粘性聚合物溶液中显示出正常的游泳速度，所述粘性聚合物溶液用于比较细菌物种之间的运动性的先前研究。然而，这些相同的突变体显示出减少的定殖，表明螺旋形状通过另一种机制促进胃感染。在这里，我们鉴定了Csd 4，一种细胞壁三肽蛋白酶，它诱导细胞体弯曲，与之前显示的促进螺旋扭曲的细胞壁交联变化无关。缺乏Csd 4的细胞形成直杆，其也显示出定殖缺陷，但在几种粘性聚合物溶液中具有正常速度。然而，在检查凝胶样介质中的运动性时，我们发现细胞曲率的消除或放大会干扰运动性。因此H.幽门螺旋的螺旋形状可能有助于凝胶状胃粘液的渗透。
Helical cell shape of the gastric pathogen Helicobacter pylori has been suggested to promote virulence through viscosity-dependent enhancement of swimming velocity. However, H. pylori csd1 mutants, which are curved but lack helical twist, show normal velocity in viscous polymer solutions and the reason for their deficiency in stomach colonization has remained unclear. Characterization of new rod shaped mutants identified Csd4, a DL-carboxypeptidase of peptidoglycan (PG) tripeptide monomers and Csd5, a putative scaffolding protein. Morphological and biochemical studies indicated Csd4 tripeptide cleavage and Csd1 crosslinking relaxation modify the PG sacculus through independent networks that coordinately generate helical shape. csd4 mutants show attenuation of stomach colonization, but no change in proinflammatory cytokine induction, despite four-fold higher levels of Nod1-agonist tripeptides in the PG sacculus. Motility analysis of similarly shaped mutants bearing distinct alterations in PG modifications revealed deficits associated with shape, but only in gel-like media and not viscous solutions. As gastric mucus displays viscoelastic gel-like properties, our results suggest enhanced penetration of the mucus barrier underlies the fitness advantage conferred by H. pylori's characteristic shape. The only habitat of Helicobacter pylori is the human stomach, where it can promote stomach ulcers and cancer. Cells lining the stomach are protected from luminal acid by a thick layer of gastric mucus composed of polymerized gastric mucins. Gastric mucin undergoes a physical transition between a viscoelastic solution at neutral pH to a viscoelastic gel-like state at low pH. Helical rod shape in bacteria has been suggested to enhance swimming velocity in viscous solutions by a cork-screw mechanism, but H. pylori mutants lacking helical twist show normal swimming velocity in viscous polymer solutions used in prior studies comparing motility across bacterial species. These same mutants, however, show diminished colonization suggesting helical shape promotes stomach infection by another mechanism. Here we identified Csd4, a protease of cell wall tripeptides, which induces curvature in the cell body independently from the changes in cell wall crosslinking previously shown to promote helical twist. Cells lacking Csd4 form straight rods that also show colonization defects but normal velocity in several viscous polymer solutions. Upon examination of motility in gel-like media, however, we discovered that elimination or exaggeration of cell curvature perturbs motility. Thus H. pylori's helical shape may aid penetration of gel-like stomach mucus.
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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
通讯作者：
Boneca IG
影响因子：
6.4
作者：
Howitt MR;Lee JY;Lertsethtakarn P;Vogelmann R;Joubert LM;Ottemann KM;Amieva MR
通讯作者：
Amieva MR
影响因子：
3.1
作者：
Eaton, KA;Suerbaum, S;Krakowka, S
通讯作者：
Krakowka, S
DOI：
10.1073/pnas.0805309105
发表时间：
2008-12-09
影响因子：
11.1
作者：
Huang, Kerwyn Casey;Mukhopadhyay, Ranjan;Wingreen, Ned S.
通讯作者：
Wingreen, Ned S.
影响因子：
6.4
作者：
HAZELL, SL;LEE, A;HENNESSY, W
通讯作者：
HENNESSY, W