Nitric oxide inhibits Shiga-toxin synthesis by enterohemorrhagic Escherichia coli
Nitric oxide inhibits Shiga-toxin synthesis by enterohemorrhagic Escherichia coli
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DOI：
10.1073/pnas.0702589104
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发表时间：
2007-06-12
影响因子：
11.1
通讯作者：
Gobert, Alain P.
中科院分区：
文献类型：
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作者：
Vareille, Marjolaine;de Sablet, Thibaut;Gobert, Alain P.
志贺毒素（Stx）是肠出血性大肠杆菌（EHEC）的主要毒力因子。编码Stx的基因由整合在细菌基因组中的类梭菌噬菌体携带，并在DNA损伤剂诱导的细菌SOS反应后完全表达。由于一氧化氮（NO）是感染的结肠粘膜的先天免疫反应的重要介质，我们的目的是确定其在肠出血性大肠杆菌的Stx生产的作用。在这里，我们证明了化学或细胞来源的NO抑制自发和丝裂霉素C诱导的Stx mRNA表达和Stx合成，而不改变EHEC的活力。STX噬菌体的合成也减少了NO。这种抑制作用显然是通过NO介导的致敏EHEC，因为突变的NO传感器亚硝酸盐敏感的阻遏物的STX表达的NO抑制活性的损失的结果。因此，我们的研究结果确定NO作为stK表达噬菌体繁殖和Stx释放的抑制剂，从而作为限制溶血综合征发展的潜在保护因子。
Shiga-toxin (Stx) is the cardinal virulence factor of enterohemorrhagic Escherichia coli (EHEC). The genes encoding Stx are carried by a lambdoid phage integrated in the bacterial genome and are fully expressed after a bacterial SOS response induced by DNA-damaging agents. Because nitric oxide (NO) is an essential mediator of the innate immune response of infected colonic mucosa, we aimed to determine its role in Stx production by EHEC. Here we demonstrate that chemical or cellular sources of NO inhibit spontaneous and mitomycin C-induced stx mRNA expression and Stx synthesis, without altering EHEC viability. The synthesis of stx phage is also reduced by NO. This inhibitory effect apparently occurs through the NO-mediated sensitization of EHEC because mutation of the NO sensor nitrite-sensitive repressor results in loss of NO inhibiting activity on stx expression. Thus our findings identify NO as an inhibitor of stK expressing-phage propagation and Stx release and thus as a potential protective factor limiting the development of hemolytic syndromes.