Identification of a PadR-type regulator essential for intracellular pathogenesis of Burkholderia pseudomallei.
Identification of a PadR-type regulator essential for intracellular pathogenesis of Burkholderia pseudomallei.
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鉴定PADR型调节剂对于Burkholderia pseudomallei的细胞内发病机理必不可少。
DOI：
10.1038/s41598-021-89852-7
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发表时间：
2021-05-17
影响因子：
4.6
通讯作者：
Hoang TT
中科院分区：
文献类型：
--
作者：
McMillan IA;Norris MH;Zarzycki-Siek J;Heacock-Kang Y;Sun Z;Borlee BR;Hoang TT
假鼻疽伯克霍尔德氏菌(BP)是热带地区地方性疾病类鼻疽的病原体。类鼻疽病以各种方式表现，从急性皮肤损害到肺炎，在极少数情况下，还表现为中枢神经系统感染。BP是一种兼性胞内病原体，可感染多种细胞类型。BP的细胞内生命周期已经被部分阐明，并且非常复杂。在这里，我们已经确定了一个转录调节因子BP1026B_II1198，它在BP通过宿主细胞时有差异表达。在RAW264.7细胞和BALB/c小鼠感染中，BP1026B_II1198的缺失突变体被减弱。为了进一步研究BP1026B_II1198的功能，我们尝试确定了BP1026B_II1198的调控基因。RNA-SEQ分析显示了调控基因的整体图像，而CHIP-SEQ分析在第二染色体上发现了两个特异的BP1026B_II1198结合区。我们研究了这些基因由BP1026B_II1198控制的转座子突变，证实了这些基因与RAW264.7小鼠巨噬细胞的发病有关。综上所述，本文提供的数据揭示了BP1026B_II1198的调控及其在细胞内感染中的作用，并强调了BP在宿主感染过程中高度复杂的调控网络的一个组成部分。
Burkholderia pseudomallei (Bp) is the causative agent of melioidosis, a disease endemic to the tropics. Melioidosis manifests in various ways ranging from acute skin lesions to pneumonia and, in rare cases, infection of the central nervous system. Bp is a facultative intracellular pathogen and it can infect various cell types. The Bp intracellular lifecycle has been partially elucidated and is highly complex. Herein, we have identified a transcriptional regulator, BP1026B_II1198, that is differentially expressed as Bp transits through host cells. A deletion mutant of BP1026B_II1198 was attenuated in RAW264.7 cell and BALB/c mouse infection. To further characterize the function of this transcriptional regulator, we endeavored to determine the regulon of BP1026B_II1198. RNA-seq analysis showed the global picture of genes regulated while ChIP-seq analysis identified two specific BP1026B_II1198 binding regions on chromosome II. We investigated the transposon mutants of these genes controlled by BP1026B_II1198 and confirmed that these genes contribute to pathogenesis in RAW264.7 murine macrophage cells. Taken together, the data presented here shed light on the regulon of BP1026B_II1198 and its role during intracellular infection and highlights an integral portion of the highly complex regulation network of Bp during host infection.
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影响因子：
14.9
作者：
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通讯作者：
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通讯作者：
Schoolnik, Gary K.