Salmonella Typhimurium's Transthyretin-Like Protein Is a Host-Specific Factor Important in Fecal Survival in Chickens
Salmonella Typhimurium's Transthyretin-Like Protein Is a Host-Specific Factor Important in Fecal Survival in Chickens
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DOI：
10.1371/journal.pone.0046675
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发表时间：
2012-12-21
期刊：
影响因子：
3.7
通讯作者：
Strugnell, Richard A.
中科院分区：
文献类型：
--
作者：
Hennebry, Sarah C.;Sait, Leanne C.;Strugnell, Richard A.
来自肠沙门氏菌I亚种的转甲状腺素样蛋白（TLP）是一种与哺乳动物和鱼类中发现的蛋白具有高度结构相似性的质周蛋白。在人体中，这种蛋白的同系物，转甲状腺素，结合并携带视黄醇和甲状腺素，以及一系列其他不相关的芳香族化合物。本研究表明，来自沙门氏菌属不同种、亚种和血清型的TLP的氨基酸序列高度保守，并证明TLP基因在鼠伤寒沙门氏菌中组成性表达，铜和其他二价金属离子严重抑制TLP酶活性，TLP是一种水解5-羟基异ourate （5-HIU）的环酰胺水解酶。为了确定鼠伤寒沙门氏菌TLP的体内作用，我们构建了一株TLP基因（SL1344 dydx）突变的鼠伤寒沙门氏菌SL1344。我们通过小鼠和鸡的口服接种评估了该菌株的毒力。虽然SL1344染料dx在这两种生物中诱导了全身感染，但与鼠伤寒沙门氏菌SL1344相比，在感染鸡的粪便中检测到的细菌负荷显著减少。这些数据表明，TLP基因是鼠伤寒沙门氏菌在高尿酸环境（如鸡粪便）中存活所必需的，并且沙门氏菌在天然宿主和人工宿主中的代谢特征可能存在根本不同。我们的数据还强调了使用适当的动物模型研究细菌发病机制的重要性，特别是在宿主特异性毒力因子或特征是研究主题的情况下。
The transthyretin-like protein (TLP) from Salmonella enterica subspecies I is a periplasmic protein with high level structural similarity to a protein found in mammals and fish. In humans, the protein homologue, transthyretin, binds and carries retinol and thyroxine, and a series of other, unrelated aromatic compounds. Here we show that the amino acid sequence of the TLP from different species, subspecies and serovars of the Salmonella genus is highly conserved and demonstrate that the TLP gene is constitutively expressed in S. Typhimurium and that copper and other divalent metal ions severely inhibit enzyme activity of the TLP, a cyclic amidohydrolase that hydrolyses 5-hydroxyisourate (5-HIU). In order to determine the in vivo role of the S. Typhimurium TLP, we constructed a strain of mouse-virulent S. Typhimurium SL1344 bearing a mutation in the TLP gene (SL1344 DyedX). We assessed the virulence of this strain via oral inoculation of mice and chickens. Whilst SL1344 DyedX induced a systemic infection in both organisms, the bacterial load detected in the faeces of infected chickens was significantly reduced when compared to the load of S. Typhimurium SL1344. These data demonstrate that the TLP gene is required for survival of S. Typhimurium in a high uric acid environment such as chicken faeces, and that metabolic traits of Salmonellae in natural and contrived hosts may be fundamentally different. Our data also highlight the importance of using appropriate animal models for the study of bacterial pathogenesis especially where host-specific virulence factors or traits are the subject of the study.