Glutathione catabolism by Enterobacteriaceae species to hydrogen sulphide adversely affects the viability of host systems in the presence of 5′fluorodeoxyuridine,Molecular Microbiology

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Glutathione catabolism by Enterobacteriaceae species to hydrogen sulphide adversely affects the viability of host systems in the presence of 5′fluorodeoxyuridine
Molecular Microbiology ( IF 2.6 ) Pub Date : 2022-03-13 , DOI: 10.1111/mmi.14893
Daniel Rui Xiang Lim ₁ , Yahua Chen ₁ , Li Fang Ng ₂ , Jan Gruber _{1,

2} , Yunn-Hwen Gan _{1,

3}

Affiliation

Reduced glutathione (GSH) plays an essential role in relieving oxidative insult from the generation of free radicals via normal physiological processes. However, GSH can be exploited by bacteria as a signalling molecule for the regulation of virulence. We describe findings arising from a serendipitous observation that when GSH and Escherichia coli were incubated with 5′fluorodeoxyuridine (FUdR)-synchronised populations of Caenorhabditis elegans, the nematodes underwent rapid death. Death was mediated by the production of hydrogen sulphide mainly through the action of tnaA, a tryptophanase-encoding gene in E. coli. Other Enterobacteriaceae species possess similar cysteine desulfhydrases that can catabolise l-cysteine-containing compounds to hydrogen sulphide and mediate nematode killing when worms had been pre-treated with FUdR. When colonic epithelial cell lines were infected, hydrogen sulphide produced by these bacteria in the presence of GSH was also able to inhibit ATP synthesis in these cells particularly when cells had been treated with FUdR. Therefore, bacterial production of hydrogen sulphide could act in concert with a commonly used genotoxic cancer drug to exert host cell impairment. Hydrogen sulphide also increases bacterial adhesion to the intestinal cells. These findings could have implications for patients undergoing chemotherapy using FUdR analogues that could result in intestinal damage.

中文翻译：

肠杆菌科细菌谷胱甘肽分解代谢为硫化氢对宿主系统在 5'氟脱氧尿苷存在下的生存能力产生不利影响

还原型谷胱甘肽 (GSH) 在通过正常生理过程缓解自由基产生的氧化损伤方面发挥着重要作用。然而，细菌可以利用 GSH 作为信号分子来调节毒力。我们描述了一个偶然观察到的发现，即当 GSH 和大肠杆菌与 5'氟脱氧尿苷 (FUdR) 同步的秀丽隐杆线虫种群一起孵育时，线虫迅速死亡。死亡是由硫化氢的产生介导的，主要是通过大肠杆菌中的色氨酸酶编码基因tnaA的作用。其他肠杆菌科细菌具有类似的半胱氨酸脱硫酶，可以分解代谢l-当用 FUdR 预处理蠕虫时，含半胱氨酸的化合物可转化为硫化氢并介导杀死线虫。当结肠上皮细胞系被感染时，这些细菌在 GSH 存在下产生的硫化氢也能够抑制这些细胞中的 ATP 合成，特别是当细胞已经用 FUdR 处理时。因此，硫化氢的细菌产生可以与一种常用的基因毒性抗癌药物协同作用，从而对宿主细胞造成损害。硫化氢还增加细菌对肠细胞的粘附。这些发现可能对使用可能导致肠道损伤的 FUdR 类似物进行化疗的患者产生影响。

更新日期：2022-03-13

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