Phospholipid Hydrolysis Caused by Clostridium perfringens α-Toxin Facilitates the Targeting of Perfringolysin O to Membrane Bilayers
Phospholipid Hydrolysis Caused by Clostridium perfringens α-Toxin Facilitates the Targeting of Perfringolysin O to Membrane Bilayers
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DOI：
10.1021/bi1013886
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发表时间：
2010-11-09
期刊：
影响因子：
2.9
通讯作者：
Heuck, Alejandro P.
中科院分区：
文献类型：
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作者：
Moe, Paul C.;Heuck, Alejandro P.
产气荚膜梭状芽胞杆菌引起人类气性坏疽和胃肠道疾病。这些病理是由强效的细胞外蛋白毒素介导的，特别是α毒素和纤溶素O （PFO）。当α -毒素水解磷脂酰胆碱和鞘磷脂时，PFO在含胆固醇的膜上形成大的跨膜孔。有人认为，PFO穿透靶细胞膜的能力取决于存在多少游离胆固醇分子。考虑到产气荚膜荚膜荚膜球菌α -毒素可使磷脂酰胆碱的磷脂胆碱头基团裂解，我们推断α -毒素可能会增加膜中游离胆固醇分子的数量。我们目前的研究表明，α -毒素在膜双层上的作用促进了PFO-胆固醇的相互作用，这可以通过减少膜中PFO结合和孔形成所需的胆固醇量来证明。这些研究提示了a-毒素和PFO在产气荚膜梭菌发病过程中协同作用的机制。
Clostridium perfringens causes gas gangrene and gastrointestinal disease in humans. These pathologies are mediated by potent extracellular protein toxins, particularly alpha-toxin and perfringolysin O (PFO). While alpha-toxin hydrolyzes phosphatidylcholine and sphingomyelin, PFO forms large transmembrane pores on cholesterol-containing membranes. It has been suggested that the ability of PFO to perforate the membrane of target cells is dictated by how much free cholesterol molecules are present. Given that C. perfringens alpha-toxin cleaves the phosphocholine headgroup of phosphatidylcholine, we reasoned that alpha-toxin may increase the number of free cholesterol molecules in the membrane. Our present studies reveal that alpha-toxin action on membrane bilayers facilitates the PFO-cholesterol interaction as evidenced by a reduction in the amount of cholesterol required in the membrane for PFO binding and pore formation. These studies suggest a mechanism for the concerted action of a-toxin and PFO during C. perfringens pathogenesis.