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Fur Is the Master Regulator of the Extraintestinal Pathogenic Escherichia coli Response to Serum

机译：皮草是肠外致病性大肠杆菌对血清反应的主要调节剂

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Drug-resistant extraintestinal pathogenic Escherichia coli (ExPEC) strains are the major cause of colisepticemia (colibacillosis), a condition that has become an increasing public health problem in recent years. ExPEC strains are characterized by high resistance to serum, which is otherwise highly toxic to most bacteria. To understand how these bacteria survive and grow in serum, we performed system-wide analyses of their response to serum, making a clear distinction between the responses to nutritional immunity and innate immunity. Thus, mild heat inactivation of serum destroys the immune complement and abolishes the bactericidal effect of serum (inactive serum), making it possible to examine nutritional immunity. We used a combination of deep RNA sequencing and proteomics in order to characterize ExPEC genes whose expression is affected by the nutritional stress of serum and by the immune complement. The major change in gene expression induced by serum—active and inactive—involved metabolic genes. In particular, the serum metabolic response is coordinated by three transcriptional regulators, Fur, BasR, and CysB. Fur alone was responsible for more than 80% of the serum-induced transcriptional response. Consistent with its role as a major serum response regulator, deletion of Fur renders the bacteria completely serum sensitive. These results highlight the role of metabolic adaptation in colisepticemia and virulence. >IMPORTANCE Drug-resistant extraintestinal pathogenic Escherichia coli (ExPEC) strains have emerged as major pathogens, especially in community- and hospital-acquired infections. These bacteria cause a large spectrum of syndromes, the most serious of which is septicemia, a condition with a high mortality rate. These bacterial strains are characterized by high resistance to serum, otherwise highly toxic to most bacteria. To understand the basis of this resistance, we carried out system-wide analyses of the response of ExPEC strains to serum by using proteomics and deep RNA sequencing. The major changes in gene expression induced by exposure to serum involved metabolic genes, not necessarily implicated in relation to virulence. One metabolic regulator—Fur—involved in iron metabolism was responsible for more than 80% of the serum-induced?response, and its deletion renders the bacteria completely serum sensitive. These results highlight the role of metabolic adaptation in virulence.
机译：耐药的肠外致病性大肠埃希菌（ExPEC）菌株是大肠埃希菌病（大肠杆菌感染）的主要病因，近年来这种病已成为日益严重的公共卫生问题。 ExPEC菌株的特征是对血清的高抗性，否则对大多数细菌具有高毒性。为了了解这些细菌如何在血清中生存和生长，我们对它们对血清的反应进行了系统范围的分析，从而明确了对营养免疫和先天免疫的反应之间的区别。因此，温和的血清失活会破坏免疫补体并消除血清（失活的血清）的杀菌作用，从而可以检查营养免疫力。我们使用深度RNA测序和蛋白质组学的组合来表征ExPEC基因，其表达受血清营养压力和免疫补体影响。血清诱导的基因表达的主要变化（活性和非活性）涉及代谢基因。特别是，血清代谢反应由三种转录调节因子Fur，BasR和CysB协调。仅毛皮引起的血清诱导的转录应答就占80％以上。与其作为主要血清反应调节剂的作用一致，Fur的缺失使细菌完全对血清敏感。这些结果突出了代谢适应在大肠埃希菌病和毒力中的作用。 >重要性耐药性肠外致病性大肠埃希菌（ExPEC）菌株已成为主要病原体，尤其是在社区和医院获得性感染中。这些细菌会导致多种综合症，其中最严重的是败血症，这是一种死亡率很高的疾病。这些细菌菌株的特征在于对血清的高抗性，否则对大多数细菌具有高毒性。为了了解这种抗药性的基础，我们通过蛋白质组学和深度RNA测序对ExPEC菌株对血清的反应进行了系统范围的分析。暴露于血清引起的基因表达的主要变化涉及代谢基因，不一定与毒力有关。参与铁代谢的一种代谢调节剂（Fur）引起了80％以上的血清诱导反应，并且其缺失使细菌完全对血清敏感。这些结果突出了代谢适应在毒力中的作用。

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