Zinc protects against Shiga-toxigenic Escherichia coli by acting on host tissues as well as on bacteria.
Zinc protects against Shiga-toxigenic Escherichia coli by acting on host tissues as well as on bacteria.
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DOI：
10.1186/1471-2180-14-145
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发表时间：
2014-06-05
期刊：
影响因子：
4.2
通讯作者：
Werth BB
中科院分区：
文献类型：
--
作者：
Crane JK;Broome JE;Reddinger RM;Werth BB
锌补充剂可以治疗或预防肠道感染和腹泻疾病。然而，许多关于细菌中锌的文章强调了这种金属对细菌生长和毒性的本质，这表明锌应该使感染恶化，而不是好转。为了解决这一矛盾，我们测试了锌是否对肠上皮和病原体有保护作用。利用T84细胞的极化单层，我们发现锌可以防止过氧化氢引起的损伤，通过测量上皮间电阻。锌还能减少过氧化物诱导的志贺毒素（Stx）在T84单分子膜上从根尖到基底外侧的移位。锌在防止过氧化物诱导的上皮损伤方面优于其他二价金属（铁、锰和镍），而铜也显示出保护作用。SOS细菌应激反应途径是产志在大肠杆菌中产生Stx的强大调节剂。我们研究了锌对Stx的已知抑制作用是否可能是通过阻断SOS反应介导的。锌降低了recA的表达，recA是SOS的可靠标志物。在抑制过氧化氢、黄嘌呤氧化酶或抗生素环丙沙星诱导的recA表达方面，锌比其他金属更有效。锌对recA/SOS和Stx的影响密切相关，表明抑制SOS反应是锌保护STEC感染的机制之一。锌对肠道细菌病原体的保护能力可能是其对宿主组织的综合作用以及对某些病原体的毒力抑制的结果。仅关注锌对致病微生物的影响的研究可能由于未能解释锌对宿主上皮的保护作用而给出不完整的图片。
Zinc supplements can treat or prevent enteric infections and diarrheal disease. Many articles on zinc in bacteria, however, highlight the essential nature of this metal for bacterial growth and virulence, suggesting that zinc should make infections worse, not better. To address this paradox, we tested whether zinc might have protective effects on intestinal epithelium as well as on the pathogen. Using polarized monolayers of T84 cells we found that zinc protected against damage induced by hydrogen peroxide, as measured by trans-epithelial electrical resistance. Zinc also reduced peroxide-induced translocation of Shiga toxin (Stx) across T84 monolayers from the apical to basolateral side. Zinc was superior to other divalent metals to (iron, manganese, and nickel) in protecting against peroxide-induced epithelial damage, while copper also showed a protective effect. The SOS bacterial stress response pathway is a powerful regulator of Stx production in STEC. We examined whether zinc’s known inhibitory effects on Stx might be mediated by blocking the SOS response. Zinc reduced expression of recA, a reliable marker of the SOS. Zinc was more potent and more efficacious than other metals tested in inhibiting recA expression induced by hydrogen peroxide, xanthine oxidase, or the antibiotic ciprofloxacin. The close correlation between zinc’s effects on recA/SOS and on Stx suggested that inhibition of the SOS response is one mechanism by which zinc protects against STEC infection. Zinc’s ability to protect against enteric bacterial pathogens may be the result of its combined effects on host tissues as well as inhibition of virulence in some pathogens. Research focused solely on the effects of zinc on pathogenic microbes may give an incomplete picture by failing to account for protective effects of zinc on host epithelia.
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影响因子：
3.7
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通讯作者：
Neyrolles O