Bacillus cereus Nhe is a pore-forming toxin with structural and functional properties similar to the ClyA (HIyE, SheA) family of haemolysins, able to induce osmotic lysis in epithelia
Bacillus cereus Nhe is a pore-forming toxin with structural and functional properties similar to the ClyA (HIyE, SheA) family of haemolysins, able to induce osmotic lysis in epithelia
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DOI：
10.1099/mic.0.2007/014134-0
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发表时间：
2008-03-01
期刊：
影响因子：
2.8
通讯作者：
Hardy, Simon P.
中科院分区：
文献类型：
--
作者：
Fagerlund, Annette;Lindback, Toril;Hardy, Simon P.
蜡状芽孢杆菌引起腹泻的机制尚不清楚。已提出三种推定的肠毒素，溶血素BL（HbI）、细胞毒素K和非溶血性肠毒素（Nhe）。HbI和Nhe都是三组分细胞毒素，Nhe对上皮细胞的最大细胞毒性依赖于所有三种组分。然而，细胞毒性的机制知之甚少。在暴露于来自B培养上清液的Nhe的上皮细胞中观察到质膜破坏的标志物，即碘化丙啶摄取、细胞ATP损失和乳酸脱氢酶（LDH）释放。蜡状芽孢杆菌，但不是在那些暴露于缺乏NheB和NheC的突变株的上清液。与膜损伤的外源性原因一致，纯化的NHE组分结合在平面脂质双层中形成大的传导孔。渗透保护剂对LDH释放的抑制和Nhe引起的细胞大小的增加表明渗透性肿胀后上皮细胞溶解。Nhe和HbI显示序列同源性，并且HbI组分B与溶细胞素A（ClyA）具有显著的结构相似性，两种结构都具有α-螺旋束和含有疏水性β-发夹的独特亚结构域。相应地，我们表明，Nhe具有溶血活性对红细胞从各种物种。我们建议，共同的结构和功能特性表明，HbI/Nhe和ClyA家族的毒素构成一个超家族的孔形成细胞毒素。
The mechanism by which Bacillus cereus causes diarrhoea is unknown. Three putative enterotoxins have been proposed, haemolysin BL (HbI), cytotoxin K and non-haemolytic enterotoxin (Nhe). Both HbI and Nhe are three-component cytotoxins and maximal cytotoxicity of Nhe against epithelia is dependent on all three components. However, little is known of the mechanism of cytotoxicity. Markers of plasma membrane disruption, namely propidium iodide uptake, loss of cellular ATP and release of lactate dehydrogenase (LDH), were observed in epithelia exposed to Nhe from culture supernatants of B. cereus, but not in those exposed to supernatants from a mutant strain lacking NheB and NheC. Consistent with an exogenous cause of membrane damage, purified Nhe components combined to form large conductance pores in planar lipid bilayers. The inhibition of LDH release by osmotic protectants and the increase in cell size caused by Nhe indicate that epithelia lyse following osmotic swelling. Nhe and HbI show sequence homology, and HbI component B has remarkable structural similarities to cytolysin A (ClyA), with both structures possessing an a-helix bundle and a unique subdomain containing a hydrophobic beta-hairpin. Correspondingly, we show that Nhe has haemolytic activity against erythrocytes from a variety of species. We propose that the common structural and functional properties indicate that the HbI/Nhe and ClyA families of toxins constitute a superfamily of pore-forming cytotoxins.