Differential spatial repositioning of activated genes in Biomphalaria glabrata snails infected with Schistosoma mansoni.
Differential spatial repositioning of activated genes in Biomphalaria glabrata snails infected with Schistosoma mansoni.
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DOI：
10.1371/journal.pntd.0003013
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发表时间：
2014-09
影响因子：
3.8
通讯作者：
Knight M
中科院分区：
文献类型：
--
作者：
Arican-Goktas HD;Ittiprasert W;Bridger JM;Knight M
血吸虫病是一种以哺乳动物为最终宿主，淡水螺为中间宿主的传染病。了解致病性寄生虫及其宿主之间的分子和生化关系将是理解和最终治疗和/或根除该疾病的关键。越来越多的证据表明，与宿主共同进化的病原体可以在不同层面上操纵宿主的行为，以增强感染。例如，细菌可以诱导宿主基因组的有益染色质重塑。我们先前已经在体外证明，光滑双脐藻胚胎细胞与嗜水气单胞菌毛蚴共培养显示基因改变其核位置并上调。这也发生在活的完整的蜗牛体内，早期暴露于毛蚴也会导致基因的非随机重新定位。我们揭示了寄生虫易感蜗牛的反应之间的核重新定位的差异相比，耐药蜗牛和正常或活的，减毒的寄生虫。有趣的是，应激反应基因热休克蛋白（Hsp）70只重新定位，然后上调易感蜗牛与正常的寄生虫。这种基因表达的运动和变化似乎是由寄生虫控制的。基因行为的其他差异支持这样的观点，即一些基因对组织损伤作出反应，例如铁蛋白基因移动并上调，无论蜗牛是易感还是抗性，以及暴露于正常或减毒寄生虫时。这是第一次在寄生宿主中看到宿主基因组重组，而对于任何病原体来说都是第二次。我们相信，寄生虫会引发宿主基因组的空间表观遗传重组，以诱导对自身有利的基因表达，这可能代表感染血吸虫尾蚴的人类宿主以及其他宿主-病原体关系中存在的基本机制。血吸虫病是一种寄生虫病，在世界许多地方流行。引起血吸虫病的寄生虫感染人类，但使用淡水蜗牛作为第二宿主。这两种生物共同进化，因此寄生虫将具有克服宿主防御的机制。了解这种微妙的平衡关系是控制或根除这种疾病的基础。我们已经研究了这种寄生虫如何影响蜗牛体内的DNA行为。我们已经证明蜗牛基因在细胞核内有特定的位置。此外，我们还发现，与病毒感染相关的特定蜗牛基因在打开或上调时会改变到一个新的非随机核位置。我们有对寄生虫感染敏感或有抵抗力的蜗牛品种，我们也可以采取活的寄生虫，通过辐射使它们无法完成感染。在这项独特的研究中，我们已经证明了一个参与应激途径的基因移动到一个新的核位置并被打开，但仅在感染了功能齐全的寄生虫的易感蜗牛中。我们的数据表明，这个基因是由寄生虫调节的，寄生虫控制着宿主的DNA，因此基因被转移到一个可以积极表达的区域。我们发现了一种新的机制，即宿主生物体的空间组织受到病原体的干扰。这种类型的控制可能在其他宿主-病原体关系中发现。
Schistosomiasis is an infectious disease infecting mammals as the definitive host and fresh water snails as the intermediate host. Understanding the molecular and biochemical relationship between the causative schistosome parasite and its hosts will be key to understanding and ultimately treating and/or eradicating the disease. There is increasing evidence that pathogens that have co-evolved with their hosts can manipulate their hosts' behaviour at various levels to augment an infection. Bacteria, for example, can induce beneficial chromatin remodelling of the host genome. We have previously shown in vitro that Biomphalaria glabrata embryonic cells co-cultured with schistosome miracidia display genes changing their nuclear location and becoming up-regulated. This also happens in vivo in live intact snails, where early exposure to miracidia also elicits non-random repositioning of genes. We reveal differences in the nuclear repositioning between the response of parasite susceptible snails as compared to resistant snails and with normal or live, attenuated parasites. Interestingly, the stress response gene heat shock protein (Hsp) 70 is only repositioned and then up-regulated in susceptible snails with the normal parasite. This movement and change in gene expression seems to be controlled by the parasite. Other differences in the behaviour of genes support the view that some genes are responding to tissue damage, for example the ferritin genes move and are up-regulated whether the snails are either susceptible or resistant and upon exposure to either normal or attenuated parasite. This is the first time host genome reorganisation has been seen in a parasitic host and only the second time for any pathogen. We believe that the parasite elicits a spatio-epigenetic reorganisation of the host genome to induce favourable gene expression for itself and this might represent a fundamental mechanism present in the human host infected with schistosome cercariae as well as in other host-pathogen relationships. Bilharzia is a parasitic disease endemic in many parts of the world. The schistosoma parasite that causes Bilharzia infects humans but uses a fresh water snail as a secondary host. These two organisms have co-evolved together, and as such the parasite will have mechanisms to overcome the host defences. Understanding this delicately balanced relationship is fundamental to controlling or eradicating the disease. We have studied how this parasite can influence how the DNA within the snail behaves. We have shown snail genes have specific locations within the cell nuclei. Further, we have revealed that specific snail genes related to a schistosome infection change to a new non-random nuclear location as they are turned on or up-regulated. We have snail strains that are susceptible or resistant to the infection of parasites and we can also take live parasites and make them unable to complete an infection by irradiating them. In this unique study, we have shown a gene that is involved in stress pathways moves to a new nuclear location and becomes turned on, but only in susceptible snails, infected with fully functional parasite. Our data suggest that this gene is regulated by the parasite, which has control over the host's DNA, so that the gene is moved to an area where it can be actively expressed. We have uncovered a novel mechanism whereby the spatial organization of a host organism is interfered with by a pathogen. This type of control is probably found in other host-pathogen relationships.
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影响因子：
1.3
作者：
Basso, W;Venturini, L;Dubey, JP
通讯作者：
Dubey, JP
DOI：
10.1083/jcb.145.6.1119
发表时间：
1999-06-14
期刊：
The Journal of cell biology
影响因子：
--
作者：
Croft JA;Bridger JM;Boyle S;Perry P;Teague P;Bickmore WA
通讯作者：
Bickmore WA
影响因子：
3.2
作者：
Fneich S;Dheilly N;Adema C;Rognon A;Reichelt M;Bulla J;Grunau C;Cosseau C
通讯作者：
Cosseau C
影响因子：
4
作者：
Knight, Matty;Ittiprasert, Wannaporn;Bridger, Joanna M.
通讯作者：
Bridger, Joanna M.
DOI：
10.1590/s0074-02762006000900027
发表时间：
2006-10-01
期刊：
Memórias do Instituto Oswaldo Cruz
影响因子：
--
作者：
Adema, Coen M;Luo, Mei-Zhong;Loker, Eric S
通讯作者：
Loker, Eric S