發(fā)布時(shí)間：2018-05-19 10:05

  本文選題：鼠疫耶爾森氏菌 + 轉(zhuǎn)錄調(diào)控　； 參考：《中國(guó)人民解放軍軍事醫(yī)學(xué)科學(xué)院》2005年博士論文

【摘要】：鼠疫是一種古老的自然疫源性疾病,其病原菌鼠疫耶爾森氏菌(以下簡(jiǎn)稱鼠疫菌)是多宿主寄生菌,體現(xiàn)在:鼠疫菌以蚤類為傳播媒介寄居在特定的宿主(主要是嚙齒動(dòng)物),并在自然界宿主中造成鼠疫疫情的周期性爆發(fā),該過程中偶然與患畜接觸或被帶菌跳蚤叮咬而感染到人。鼠疫菌感染機(jī)體早期能在巨噬細(xì)胞內(nèi)存活并繁殖,目前認(rèn)為巨噬細(xì)胞內(nèi)存活與繁殖獲得致病能力是鼠疫菌得以最終致病的關(guān)鍵階段。 面對(duì)上述復(fù)雜的環(huán)境因素,鼠疫菌必須能夠感應(yīng)并快速適應(yīng)每個(gè)環(huán)節(jié)的環(huán)境變化,才能最終在宿主體內(nèi)存活和在自然界中傳播并最終致病,而每個(gè)適應(yīng)性反應(yīng)也必然伴隨著鼠疫菌基因轉(zhuǎn)錄改變。依據(jù)上述傳播和感染過程中鼠疫菌可能面臨的脅迫環(huán)境,我們?cè)O(shè)計(jì)并實(shí)施了多個(gè)體外模擬刺激條件的轉(zhuǎn)錄譜分析,包括溫度(生長(zhǎng)溫度、冷休克和熱休克)、滲透壓(高鹽、高滲和OmpR調(diào)控元)、H_2O_2(H_2O2刺激元和OxyR調(diào)控元)、低鎂(低鎂刺激元和PhoP調(diào)控元)等刺激因素。 經(jīng)過全基因組DNA芯片單個(gè)體外條件的轉(zhuǎn)錄譜分析,我們分別得到了本研究多個(gè)體外條件下鼠疫菌在細(xì)胞代謝和毒力等方面的特征轉(zhuǎn)錄譜。野生株與突變株的比較轉(zhuǎn)錄譜分析得到鼠疫菌調(diào)節(jié)蛋白OmpR、OxyR和PhoP在特定條件下可能調(diào)節(jié)的基因,為今后調(diào)節(jié)網(wǎng)絡(luò)的研究提供調(diào)控元的靶標(biāo)基因。更重要的是,我們將上述轉(zhuǎn)錄譜以及目前本實(shí)驗(yàn)室所有的體外條件轉(zhuǎn)錄譜結(jié)果中各個(gè)基因的轉(zhuǎn)錄數(shù)據(jù)進(jìn)行匯總,歸納總結(jié)了目前已知毒力相關(guān)基因在本研究體外條件的轉(zhuǎn)錄規(guī)律,豐富了現(xiàn)有關(guān)于毒力相關(guān)基因的研究成果;通過聚類分析,并利用統(tǒng)計(jì)學(xué)分析方法對(duì)鼠疫菌基因組內(nèi)在多個(gè)條件下共轉(zhuǎn)錄的基因或基因簇進(jìn)行分析,最終預(yù)測(cè)了鼠疫菌基因組中39個(gè)可能的操縱子;根據(jù)聚類分析結(jié)果,結(jié)合基因組序列和注釋信息,對(duì)部分基因和操縱子的功能進(jìn)行預(yù)測(cè)。上述結(jié)果為鼠疫菌基因轉(zhuǎn)錄調(diào)控網(wǎng)絡(luò)的構(gòu)建及某些基因功能的預(yù)測(cè)提供了部分實(shí)驗(yàn)證據(jù),有助于深入認(rèn)識(shí)鼠疫菌的致病性及宿主-細(xì)菌間相互作用。
[Abstract]:Yersinia pestis is an ancient natural disease. Yersinia pestis (hereinafter referred to as Yersinia pestis) is a multi-host parasite. This is reflected in the fact that Yersinia pestis live in specific hosts (mainly rodents) with fleas as a vector of transmission, and cause periodic outbreaks of plague in natural hosts. This process occasionally contacts with infected animals or is infected with humans by the bite of bacterial fleas. Yersinia pestis can survive and reproduce in macrophages in the early stage of infection. At present, it is considered that survival and reproduction in macrophages is the key stage for Yersinia pestis to finally cause disease. In the face of these complex environmental factors, Yersinia pestis must be able to sense and adapt quickly to each environmental change in order to eventually survive in the host and spread in nature and eventually cause disease. And every adaptive response must be accompanied by gene transcription changes in Yersinia pestis. Based on the stress that Yersinia pestis may face during transmission and infection, we have designed and performed transcription profiling of several simulated stimuli in vitro, including temperature (growth temperature, cold shock and heat shock), osmotic pressure (high salt), Hyperosmotic and OmpR regulators were found to be stimulating factors such as H _ 2O _ 2 and H _ 2O _ 2 stimulators and OxyR regulators, and low magnesium (low magnesium stimulators and PhoP regulators). Based on the analysis of transcriptional profiles of the whole genome DNA microarray in vitro, we obtained the characteristic transcripts of Yersinia pestis in cell metabolism and virulence under several conditions in vitro. The transcriptional analysis of wild strains and mutants obtained the genes that OmpR- OxyR and PhoP might regulate under specific conditions, which provided the target genes for the future study of regulatory networks. More importantly, we put together the transcription data of each gene in all of our lab's in vitro conditional transcripts. Summarized the transcriptional rules of virulence related genes in this study in vitro, enriched the existing research results of virulence related genes. Finally, 39 possible manipulators in Yersinia pestis genome were predicted by means of statistical analysis, which was based on the results of cluster analysis, based on the analysis of genes or gene clusters cotranscribed under many conditions in the genome of Yersinia pestis (Yersinia pestis). The functions of some genes and operons were predicted by combining genomic sequences and annotated information. These results provide some experimental evidence for the construction of gene transcriptional regulatory network and prediction of some gene functions of Yersinia pestis, which is helpful to further understand the pathogenicity of Yersinia pestis and the interaction between host and bacteria.
【學(xué)位授予單位】：中國(guó)人民解放軍軍事醫(yī)學(xué)科學(xué)院
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2005
【分類號(hào)】：R378

【引證文獻(xiàn)】

相關(guān)期刊論文 前2條

1 馬立芝;高鶴;張義全;譚亞芳;郭兆彪;楊瑞馥;周冬生;;不同生長(zhǎng)時(shí)期鼠疫耶爾森菌調(diào)控子Fis轉(zhuǎn)錄譜的比較分析[J];生物技術(shù)通訊;2011年02期

2 尉研;袁媛;曾小濤;江華;鄭玉玲;周冬生;姜永強(qiáng);;豬鏈球菌2型強(qiáng)毒株S.suis 05ZY和弱毒株S.suis 1940的比較轉(zhuǎn)錄譜分析[J];生物技術(shù)通訊;2012年01期

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本文編號(hào)：1909679