The Yersiniabactin Transport System Is Critical for the Pathogenesis of Bubonic and Pneumonic Plague
The Yersiniabactin Transport System Is Critical for the Pathogenesis of Bubonic and Pneumonic Plague
复制标题
DOI：
10.1128/iai.01236-09
复制
发表时间：
2010-05-01
影响因子：
3.1
通讯作者：
Perry, Robert D.
中科院分区：
文献类型：
--
作者：
Fetherston, Jacqueline D.;Kirillina, Olga;Perry, Robert D.
从宿主获得铁是致病过程中的重要步骤。虽然鼠疫耶尔森氏菌具有多种铁转运蛋白，但耶尔森氏杆菌素（Ybt）铁载体依赖性系统在体外和体内铁获取中起主要作用。在这项研究中，我们确定了Ybt系统所需的铁结合转铁蛋白和乳铁蛋白的使用和检查的重要性，Ybt系统的毒力在小鼠模型的腺鼠疫和肺鼠疫。Y.不能运输Ybt或不能合成铁载体的鼠疫突变体通过皮下注射基本上都是无毒的（腺鼠疫模型）。令人惊讶的是，通过鼻内滴注（肺鼠疫模型），我们看到了Ybt生物合成和转运突变体的毒力差异。Ybt生物合成突变体的半数致死量（LD_（50））比转运突变体高24倍。相反，在体外铁限制条件下，Ybt转运突变体比Ybt生物合成突变体具有更严重的生长缺陷。最后，一个三角洲pgm突变体有一个更大的损失比Ybt生物合成突变体的毒力，表明102 kb的pgm基因座编码的毒力因子，除了Ybt，在肺鼠疫的发病机制中发挥作用。
Iron acquisition from the host is an important step in the pathogenic process. While Yersinia pestis has multiple iron transporters, the yersiniabactin (Ybt) siderophore-dependent system plays a major role in iron acquisition in vitro and in vivo. In this study, we determined that the Ybt system is required for the use of iron bound by transferrin and lactoferrin and examined the importance of the Ybt system for virulence in mouse models of bubonic and pneumonic plague. Y. pestis mutants unable to either transport Ybt or synthesize the siderophore were both essentially avirulent via subcutaneous injection (bubonic plague model). Surprisingly, via intranasal instillation (pneumonic plague model), we saw a difference in the virulence of Ybt biosynthetic and transport mutants. Ybt biosynthetic mutants displayed an similar to 24-fold-higher 50% lethal dose (LD50) than transport mutants. In contrast, under iron-restricted conditions in vitro, a Ybt transport mutant had a more severe growth defect than the Ybt biosynthetic mutant. Finally, a Delta pgm mutant had a greater loss of virulence than the Ybt biosynthetic mutant, indicating that the 102-kb pgm locus encodes a virulence factor, in addition to Ybt, that plays a role in the pathogenesis of pneumonic plague.