本文選題：DNA損傷 + 堿基切除修復(fù)　； 參考：《西南大學(xué)》2010年碩士論文

【摘要】： 目前結(jié)核病仍然是全球人類健康的主要威脅,原發(fā)性耐藥在耐藥結(jié)核病產(chǎn)生中占主導(dǎo)地位。全球約有17-20億的人感染結(jié)核分枝桿菌(Mycobacterium tuberculosis,即結(jié)核菌或M.tuberculosis),病人約有2000萬,每年感染M.tuberculosis的患者有約3000萬,在800萬的新患者中,約200萬死于該病。近幾年間,我們不斷加大結(jié)核病,瘧疾以及艾滋病這三大疾病的處理力度,在世界衛(wèi)生組織公布的22個(gè)限制結(jié)核控制成效的高負(fù)擔(dān)國中,中國和印度已成為結(jié)核病最多的兩個(gè)國家。M. tuberculosis的潛伏感染直接導(dǎo)致了結(jié)核病治療療程長,療效差,以及化療后易復(fù)發(fā)等,因?yàn)榀煶涕L,不能負(fù)擔(dān)所需的醫(yī)療費(fèi)用,病人不能充分化療,這也是結(jié)核病高復(fù)發(fā)率及耐藥病例增多的原因,同時(shí)也是結(jié)核病難治愈的原因。 維持基因組穩(wěn)定是生物生存的基礎(chǔ)。堿基切除修復(fù)(Base Excision Repair, BER)是DNA修復(fù)的主要方式之一。堿基切除修復(fù)對結(jié)核分枝桿菌等胞內(nèi)致病菌尤其重要。fpg是堿基切除修復(fù)的關(guān)鍵酶。通過比較分枝桿菌的基因組,發(fā)現(xiàn)結(jié)核菌較其他非致病分枝桿菌普遍具有堿基切除修復(fù)基因。這提示堿基切除修復(fù)可能與結(jié)核菌在宿主體內(nèi)存活和致病有關(guān)。這條途徑也許是新結(jié)核病藥物研發(fā)的重要靶標(biāo)。 本研究針對此現(xiàn)狀,在大腸桿菌中克隆表達(dá)結(jié)核分枝桿菌H37Rv -fpg,再經(jīng)IPTG誘導(dǎo),Ni2+ Sepharose純化重組蛋白,針對該蛋白開展進(jìn)一步的研究,以期得到相關(guān)的信息。論文還比較了重組菌和空載轉(zhuǎn)化菌株對雙氧水和UV輻射的抗性,探討了結(jié)核菌fpg基因在其中的功能。
[Abstract]:At present, tuberculosis is still a major threat to global human health, and primary drug resistance plays a leading role in the development of drug resistant tuberculosis. About 17-2 billion people worldwide are infected with Mycobacterium tuberculosis-Mycobacterium tuberculosis.There are about 20 million patients infected with Mycobacterium tuberculosus and 30 million patients infected with M. tuberculosis each year, and about 2 million of the 8 million new patients die of the disease. In recent years, we have been increasing our efforts to address the three major diseases of tuberculosis, malaria and AIDS, among the 22 high-burden countries that the World Health Organization has announced to limit the effectiveness of TB control. China and India have become the two countries with the largest number of TB cases. The latent infection of M. tuberculosis has directly resulted in long course of treatment, poor curative effect, and easy recurrence after chemotherapy, because the course of treatment is too long to afford the necessary medical expenses. Insufficient chemotherapy is the reason for the high recurrence rate of TB and the increase of drug resistant cases, as well as the difficult cure for TB. Maintaining genomic stability is the basis of biological survival. Base excision repair (ber) is one of the main methods of DNA repair. Base excision repair is especially important for mycobacterium tuberculosis and other intracellular pathogens. FPG is the key enzyme of base excision repair. By comparing the genomes of Mycobacterium spp., it was found that Mycobacterium tuberculosis had the base excision repair gene more commonly than other non-pathogenic mycobacteria. This suggests that base excision and repair may be related to the survival and pathogenicity of tuberculous bacteria in the host. This approach may be an important target for the development of new TB drugs. In this study, Mycobacterium tuberculosis H37Rv-fpgwas cloned and expressed in Escherichia coli, and then purified by IPTG induced Ni2 Sepharose. Further research on the recombinant protein was carried out in order to obtain relevant information. The resistance to hydrogen peroxide and UV radiation of recombinant and no-load transformed strains were compared, and the function of fpg gene of tuberculous bacillus was discussed.
【學(xué)位授予單位】：西南大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2010
【分類號】：R378

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 梅建;薛楨;沈鑫;沈國妙;桂曉紅;沈梅;高謙;;原發(fā)性耐藥是耐藥結(jié)核病產(chǎn)生的重要原因[J];中華結(jié)核和呼吸雜志;2006年02期

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本文編號：2047588