Shigella flexneri is the causative agent of dysentery. For pathogens, iron is a critical micronutrient as its bioavailability is usually low in bacterial niches. This metal is involved in critical physiological processes mainly as a component of important metabolic molecules involved in redox reactions. Usually bacteria respond to fluctuations in iron availability to regulate iron acquisition and other iron-related functions. Recently the close metabolic feedback between iron and riboflavin, another pivotal biological redox agent, began to draw attention in bacteria. This is a widespread biological phenomenon, partly characterized by the coordination of regulatory responses to iron and riboflavin, probably owed to the involvement of these cofactors in common processes. Nonetheless, no systematic analyses to determine the extent of this regulatory effect have been performed in any species. Here, the transcriptomics responses to iron, riboflavin, iron in the presence of riboflavin and riboflavin in the presence of iron were assessed and compared in S. flexneri. The riboflavin regulon had a 43% overlap with the iron regulon. Notably, the presence of riboflavin highly increased the number of iron-responsive genes. Reciprocally, iron drastically changed the pool of riboflavin-responsive genes. Gene ontology (GO) functional terms enrichment analysis showed that biological processes were distinctively enriched for each subgroup of responsive genes. Among the biological processes regulated by iron and riboflavin were iron uptake, amino acids metabolism and electron transfer for ATP synthesis. Thus, iron and riboflavin highly affect the transcriptomics responses induced by each other in S. flexneri. GO terms analysis suggests that iron and riboflavin coordinately regulate specific physiological functions involving redox metabolism.

中文翻译：

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通过整合转录组学确定铁和核黄素在食源性病原体志贺氏菌中调节作用的相互依赖性

志贺氏菌是痢疾的病原体。对于病原体，铁是一种关键的微量营养素，因为它在细菌生态位中的生物利用度通常较低。这种金属主要作为参与氧化还原反应的重要代谢分子的组成部分参与关键的生理过程。通常细菌会对铁可用性的波动做出反应，以调节铁的获取和其他与铁相关的功能。最近，铁和核黄素（另一种关键的生物氧化还原剂）之间的密切代谢反馈开始引起细菌的注意。这是一种广泛存在的生物学现象，部分特征在于对铁和核黄素的调节反应的协调，这可能是由于这些辅因子参与了共同的过程。尽管如此，尚未在任何物种中进行系统分析来确定这种调节作用的程度。在这里，对铁、核黄素、存在核黄素时的铁和存在铁时的核黄素的转录组学反应在弗氏链球菌中进行了评估和比较。核黄素调节子与铁调节子有 43% 的重叠。值得注意的是，核黄素的存在大大增加了铁反应基因的数量。相反，铁极大地改变了核黄素反应基因库。基因本体 (GO) 功能术语富集分析表明，每个响应基因亚组的​​生物过程都显着富集。受铁和核黄素调节的生物过程包括铁摄取、氨基酸代谢和用于 ATP 合成的电子转移。因此，铁和核黄素高度影响弗氏链球菌中相互诱导的转录组学反应。GO 术语分析表明，铁和核黄素协同调节涉及氧化还原代谢的特定生理功能。