本文選題：沙眼衣原體　切入點：大環(huán)內(nèi)酯類　出處：《天津醫(yī)科大學(xué)》2010年碩士論文

【摘要】： 目的：沙眼衣原體是一種嚴(yán)格的細(xì)胞內(nèi)寄生的微生物,感染人體后可以引起結(jié)膜炎、性病性淋巴肉芽腫和泌尿系疾病。此外,持續(xù)沙眼衣原體感染可以導(dǎo)致不孕。有報道沙眼衣原體感染可能與是男性不育有關(guān)。眾所周知,世界范圍內(nèi)D-K型沙眼衣原體血清變種(血清型)中是最常見的引起性傳播疾病的微生物。最近的研究表明,沙眼衣原體E型感染精子后大大降低精子活力和生存能力,這可能導(dǎo)致男性的不孕。目前,治療沙眼衣原體感染一線推薦使用的藥物是四環(huán)素類和大環(huán)內(nèi)酯類的阿奇霉素。大環(huán)內(nèi)酯類藥物已使用數(shù)十年,對大部分致病菌有效�？股卦卺t(yī)學(xué)和畜牧業(yè)的廣泛使用導(dǎo)致抗生素接二連三出現(xiàn)耐藥,大環(huán)內(nèi)酯類抗生素也不例外。各種微生物對大環(huán)內(nèi)酯類抗生素耐藥往往與核糖體蛋白基因的突變,特別是在L4及L22,以及在23S rRNA基因突變肽轉(zhuǎn)移區(qū)有關(guān)。然而,沙眼衣原體臨床耐藥株報道相對較少。一種解釋認(rèn)為可能是因為生物體獨特的發(fā)展周期。由于沙眼衣原體基因復(fù)制發(fā)生在感染的上皮細(xì)胞的包涵體中,從其他組織獲得抗生素耐藥基因是困難的。本文就沙眼衣原體對大環(huán)內(nèi)酯類藥物的可能分子耐藥機制進行探討。 方法：目前有報道稱磺胺類、青霉素類、利福平和氟喹諾酮類藥物次抑菌濃度誘導(dǎo)沙眼衣原體選擇性耐藥株已在實驗室獲得。我們有理由認(rèn)為次抑菌濃度的抗生素選擇壓力下可以導(dǎo)致點突變。13例沙眼衣原體臨床敏感株經(jīng)紅霉素、阿奇霉素、交沙霉素次抑菌濃度誘導(dǎo)耐藥后與未耐藥之前的敏感株和標(biāo)準(zhǔn)株E-UW-5/Cx比較,檢測基因23S rRNA和核糖體蛋白L4的位點突變。 結(jié)果：耐藥株顯現(xiàn)出對紅霉素、阿奇霉素和交沙霉素低耐藥性,MIC較敏感株分別增加了16、16、8倍。藥物敏感性結(jié)果顯示相對于紅霉素、阿奇霉素,沙眼衣原體治療交沙霉素的易感性最好。敏感株和耐藥株的L4的PCR擴增產(chǎn)物的序列均出現(xiàn)G274A、C276T、C339T、C466G位點突變,考慮與大環(huán)內(nèi)酯類藥物耐藥無關(guān)。耐藥株的23S rRNA基因PCR擴增產(chǎn)物中出現(xiàn)了A2057G、A2059G、G2093T和T2611C的突變。 結(jié)論：沙眼衣原體對大環(huán)內(nèi)酯類藥物的耐藥分子基礎(chǔ)是23S rRNA基因的點突變。
[Abstract]:Objective: chlamydia trachomatis is a strict microorganism that can cause conjunctivitis, venereal lymphogranuloma and urinary diseases.In addition, persistent chlamydia trachomatis infection can lead to infertility.Chlamydia trachomatis infection has been reported to be related to male infertility.It is well known that D-K Chlamydia trachomatis serovariants (serotypes) are the most common bacteria causing sexually transmitted diseases (STDs) worldwide.Recent studies have shown that chlamydia trachomatis E-infected sperm significantly reduces sperm motility and viability, which may lead to infertility in men.Currently, the first recommended drug for treatment of chlamydia trachomatis infection is tetracycline and macrolide azithromycin.Macrolides have been used for decades and are effective against most pathogens.The widespread use of antibiotics in medicine and animal husbandry has led to the emergence of antibiotic resistance one after another, and macrolide antibiotics are no exception.Microbial resistance to macrolides is often associated with mutations in ribosomal protein genes, especially in L4 and L22, and in the 23s rRNA gene mutational peptide transfer region.However, relatively few clinical chlamydia trachomatis resistant strains have been reported.One explanation is that it may be because of the unique developmental cycle of organisms.Because Chlamydia trachomatis gene replication occurs in the inclusion bodies of infected epithelial cells, it is difficult to obtain antibiotic resistant genes from other tissues.The possible molecular resistance mechanism of chlamydia trachomatis to macrolides was discussed.Methods: it has been reported that the selective chlamydia trachomatis resistant strains induced by sulfanilamide penicillin rifampicin and fluoroquinolones have been obtained in laboratory.We have reason to think that the antibiotic selection pressure of secondary inhibitory concentration can lead to point mutation. 13 cases of Chlamydia trachomatis clinical sensitive strains were treated with erythromycin, azithromycin,The gene 23s rRNA and ribosomal protein L4 locus mutation were detected after induced drug resistance by josamycin subinhibitory concentration compared with sensitive and standard strains before drug resistance.Results: the low resistance MIC of the resistant strains to erythromycin, azithromycin and josamycin increased by 16 16 times, respectively.The results of drug sensitivity showed that compared with erythromycin, azithromycin and chlamydia trachomatis, the susceptibility to josamycin was the best.The sequence of PCR amplification products of L4 in both susceptible and resistant strains showed G274A C276TN C339TnC466G mutation, which was not related to macrolide resistance.The mutation of A2057GN, A2059GFG, G2093T and T2611C was found in the PCR products of 23s rRNA gene of drug-resistant strain.Conclusion: the molecular basis of chlamydia trachomatis resistance to macrolides is the point mutation of 23s rRNA gene.
【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2010
【分類號】：R759

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