Enterohemorrhagic Escherichia coli (EHEC) causes serious foodborne disease worldwide. It produces the very potent Shiga toxin 2 (Stx2). The Stx2-encoding genes are located on a prophage, and production of the toxin is linked to the synthesis of Stx phages. There is, currently, no good treatment for EHEC infections, as antibiotics may trigger lytic cycle activation of the phages and increased Stx production. This study addresses how four analogs of vitamin K, phylloquinone (K1), menaquinone (K2), menadione (K3), and menadione sodium bisulfite (MSB), influence growth, Stx2-converting phage synthesis, and Stx2 production by the EHEC O157:H7 strain EDL933. Menadione and MSB conferred a concentration-dependent negative effect on bacterial growth, while phylloquinone or menaquinone had little and no effect on bacterial growth, respectively. All four vitamin K analogs affected Stx2 phage production negatively in uninduced cultures and in cultures induced with either hydrogen peroxide (H₂O₂), ciprofloxacin, or mitomycin C. Menadione and MSB reduced Stx2 production in cultures induced with either H₂O₂ or ciprofloxacin. MSB also had a negative effect on Stx2 production in two other EHEC isolates tested. Phylloquinone and menaquinone had, on the other hand, variable and concentration-dependent effects on Stx2 production. MSB, which conferred the strongest inhibitory effect on both Stx2 phage and Stx2 production, improved the growth of EHEC in the presence of H₂O₂ and ciprofloxacin, which could be explained by the reduced uptake of ciprofloxacin into the bacterial cell. Together, the data suggest that vitamin K analogs have a growth- and potential virulence-reducing effect on EHEC, which could be of therapeutic interest.

中文翻译：

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维生素K类似物会影响肠出血性大肠杆菌的生长和毒性。

肠出血性大肠杆菌（EHEC）在世界范围内引起严重的食源性疾病。它产生非常有效的志贺毒素2（Stx2）。编码Stx2的基因位于噬菌体上，毒素的产生与Stx噬菌体的合成有关。目前，对于EHEC感染尚无良好的治疗方法，因为抗生素可能会触发噬菌体的裂解周期活化并增加Stx的产生。这项研究探讨了EHEC O157的四种维生素K，叶绿体醌（K1），甲萘醌（K2），甲萘醌（K3）和甲萘醌亚硫酸氢钠（MSB）的类似物如何影响生长，Stx2转化噬菌体合成和Stx2的产生： H7菌株EDL933。甲萘醌和MSB对细菌的生长具有浓度依赖性的负面影响，而叶绿醌或甲萘醌分别对细菌的生长几乎没有影响。₂ O ₂），环丙沙星或丝裂霉素C。甲萘醌和MSB降低了H ₂ O ₂或环丙沙星诱导的培养物中Stx2的产生。MSB还对另外两个测试的EHEC分离株的Stx2产生有负面影响。另一方面，苯醌和甲萘醌对Stx2的产生具有可变和浓度依赖性的影响。MSB赋予Stx2噬菌体和Stx2产生最强的抑制作用，在H ₂ O ₂存在下改善了EHEC的生长环丙沙星和环丙沙星，这可以通过减少环丙沙星对细菌细胞的吸收来解释。总之，数据表明维生素K类似物对EHEC具有生长和潜在的降低毒力的作用，这可能具有治疗意义。