The impact of iron acquisition systems in Yersinia virulence.

铁的供应是病原菌成功存活和有效传播的先决条件。致病性耶尔森菌具有多个铁转运系统，但只有一个内源性耶尔森吸铁蛋白（Ybt）生物合成系统。然而，并不是所有的高致病性耶尔森菌都使用耶尔森菌abactin。近一半的假结核杆菌O:3株不含Ybt，但表现出铁载体活性。通过基因组减法杂交，我们证明了yptb3290-yptb3298簇可能负责这种被称为假螯合素（Pch）的铁载体的产生。为了证明pch基因对铁载体产生的影响，我们灭活了铁载体阳性假结核杆菌O:3中潜在的铁载体生物合成基因yptb3297。构建的突变体没有铁结合活性，但在长时间培养后仍能检测到相对较低的铁载体活性。在鼠疫杆菌中也检测到残留的铁载体活性，并将其命名为yersinachelin （Ych）。我们认为ysu基因簇（Yersinia siderophore uptake）负责yersinachelin的产生。为了解决这两种未表征的铁载体的性质及其在耶尔森菌致病性中的作用，我们正在构建单个铁载体系统和双突变体的突变体小组。对假螯合素和叶尔辛螯合素铁载体进行了纯化和生物化学表征，并对其结构进行了测定。杂环假螯合素的分子量为406 Da，而羟基耶尔辛螯合素的分子量为610 Da。我们想解决假螯合蛋白和耶尔森氏菌铁载体在铁获取、致病性和适应性中的作用，并阐明它们在耶尔森氏菌铁获取系统的层次结构中的位置。

Iron supply is a prerequisite for successful survival and efficient dissemination of pathogenic bacteria. The pathogenic Yersinia possess several iron transport systems but only a single endogenous yersiniabactin siderophore (Ybt) biosynthetic system. However, not all highly-pathogenic yersiniae use yersiniabactin. Nearly half of Y. pseudotuberculosis O:3 strains do not possess Ybt but display siderophore activity. Using genomic subtractive hybridization we demonstrated that the yptb3290-yptb3298 cluster might be responsible for production of this siderophore designated as pseudochelin (Pch). To prove the impact of the pch genes in siderophore production we inactivated a potential siderophore biosynthetic gene yptb3297 in the siderophore-positive Y. pseudotuberculosis O:3. The constructed mutant demonstrated no iron binding activity however relatively low siderophore activity can still be detected after prolonged cultivation. This residual siderophore activity also detected in Y. pestis was designated as yersiniachelin (Ych). We propose that the ysu gene cluster (Yersinia siderophore uptake) is responsible for yersiniachelin production. To address the nature of these two uncharacterized siderophores and their role in Yersinia pathogenicity we are constructing a panel of mutants in individual siderophore systems and double mutants. The pseudochelin and yersiniachelin siderophores have been purified and characterized biochemically and their structures will be determined. The molecular mass of the heterocyclic pseudochelin is 406 Da, while hydroxamate yersiniachelin is 610 Da. We would like to address the role of pseudochelin and yersiniachelin siderophores in iron acquisition, pathogenicity and fitness as well as to elucidate their place in a hierarchy of iron acquisition systems in Yersinia.