本文選題：淋球菌 + 基因分型　； 參考：《北京協(xié)和醫(yī)學(xué)院》2011年博士論文

【摘要】：淋病奈瑟菌(簡(jiǎn)稱淋球菌)是淋病的病原體,可引起尿道炎、宮頸炎等。阿奇霉素是我國(guó)尿道炎、宮頸炎常用治療藥物之一,臨床癥狀不典型的淋病患者可能只接受到阿奇霉素治療,故開展淋球菌對(duì)阿奇霉素的敏感性監(jiān)測(cè)是非常有意義的。與阿奇霉素不同,頭孢曲松作為目前淋病一線治療藥物,一直是我國(guó)淋球菌耐藥監(jiān)測(cè)藥物之一,監(jiān)測(cè)結(jié)果顯示近年來(lái)淋球菌對(duì)頭孢曲松的敏感性下降趨勢(shì)比較明顯,故開展淋球菌對(duì)頭孢曲松的耐藥機(jī)制研究顯得越來(lái)越重要。淋球菌多抗原序列分型方法(NG-MAST)是一種操作簡(jiǎn)便、分型能力強(qiáng)的基因分型方法,本研究應(yīng)用NG-MAST方法分析耐阿奇霉素淋球菌和頭孢曲松低敏株的基因型別和菌株間的進(jìn)化關(guān)系,為淋病防治工作提供參考依據(jù)。全文分為3個(gè)部分,各部分的主要內(nèi)容簡(jiǎn)述如下： 第一部分南京和重慶地區(qū)淋球菌對(duì)阿奇霉素的敏感性測(cè)定 本部分旨在了解南京和重慶地區(qū)淋球菌對(duì)阿奇霉素的敏感性。選取2008年及2009年南京和重慶地區(qū)分離的318株淋球菌,采用瓊脂稀釋法測(cè)定阿奇霉素、頭孢曲松、大觀霉素、四環(huán)素、環(huán)丙沙星對(duì)這318株淋球菌的最低抑菌濃度(MIC),耐阿奇霉素淋球菌定義為每批實(shí)驗(yàn)中大于或等于阿奇霉素對(duì)質(zhì)控菌株WHO P(阿奇霉素耐藥株)的MIC值的菌株。318株淋球菌中有17株(5.3%)淋球菌對(duì)阿奇霉素耐藥。 第二部分耐阿奇霉素淋球菌的NG-MAST基因分型研究 本部分旨在了解南京和重慶地區(qū)耐阿奇霉素淋球菌的基因型別和菌株間的進(jìn)化關(guān)系。對(duì)第一部分檢測(cè)出的17株耐阿奇霉素淋球菌進(jìn)行NG-MAST基因分型,并利用Mega軟件作進(jìn)化樹分析。17株耐阿奇霉素淋球菌共有11種NG-MAST基因型別,其中5種為新注冊(cè)的基因型別。有6株菌的基因型別(ST)為ST3356,2株高度耐阿奇霉素的菌株(MIC64mg/L)具有相同的基因型別ST1866�；蛐蛣eST3367及4種新注冊(cè)的基因型別與菌株數(shù)最多的基因型別ST3356親緣關(guān)系較近,可能均為短傳播鏈上同一來(lái)源菌株。 第三部分頭孢曲松低敏淋球菌的penA、porB、mtrR基因多態(tài)性研究 本部分旨在了解penA、porB、mtrR基因多態(tài)性在淋球菌對(duì)頭孢曲松敏感性下降中的作用。選取第一部分檢測(cè)出的17株頭孢曲松低敏株和4株頭孢曲松敏感株進(jìn)行penA、porB、mtrR基因測(cè)序和NG-MAST基因分型。21株淋球菌的penA基因編碼的青霉素結(jié)合蛋白2(PBP2)中共發(fā)現(xiàn)9種氨基酸結(jié)構(gòu)模式,其中2種未報(bào)道過。有8株頭孢曲松低敏株中存在ⅩⅧ型PBP2,有4株頭孢曲松低敏株中存在ⅩⅢ型PBP2,未發(fā)現(xiàn)鑲嵌狀結(jié)構(gòu)模式(X)PBP2。有18株淋球菌含有porB1b基因(編碼PorB1b蛋白),PorB1b中I218M、M257T/M257R和G259V氨基酸置換都只在頭孢曲松低敏株中出現(xiàn)。21株淋球菌的1mtrR基因編碼的MtrR中存在A39T或G45D或H105Y氨基酸置換,A39T氨基酸置換只在3株頭孢曲松低敏株中出現(xiàn),G45D或H105Y氨基酸置換在頭孢曲松低敏株和頭孢曲松敏感株中均出現(xiàn)。17株頭孢曲松低敏株共有13種NG-MAST基因型別,其中3種為新注冊(cè)的基因型別。PENa、porB、mtrR基因多態(tài)性可能在淋球菌對(duì)頭孢曲松敏感性下降中起一定作用。
[Abstract]:Neisseria gonorrhoeae (Neisseria gonorrhoeae) is the pathogen of gonorrhea, which can cause urethritis and cervicitis. Azithromycin is one of the commonly used medications in Chinese urethritis and cervicitis. The patients with atypical gonorrhea may only receive azithromycin treatment. Therefore, it is of great significance to monitor the sensitivity of azithromycin to the gonorrhoeae. Unlike azithromycin, ceftriaxone is one of the first line treatment drugs for gonorrhea. It has been one of the drug resistance monitoring drugs of gonococcus in China. The monitoring results show that the tendency of gonococcus to ceftriaxone is more obvious in recent years. Therefore, it is becoming more and more important to carry out the study of the drug resistance mechanism of gonococcus to ceftriaxone. The original sequence classification method (NG-MAST) is a simple and highly typed genotyping method. This study applies the NG-MAST method to analyze the evolutionary relationship between the genotypes and the strains of the azithromycin resistant Neisseria gonorrhoeae and ceftriaxone low sensitive strains, and provides the reference basis for the prevention and treatment of gonorrhea. The full text is divided into 3 parts, the main parts of each part The following is as follows:
Part 1 sensitivity of Neisseria gonorrhoeae to azithromycin in Nanjing and Chongqing
The purpose of this section is to understand the sensitivity of gonococci to azithromycin in Nanjing and Chongqing. Select 318 strains of gonococcus isolated from Nanjing and Chongqing in 2008 and 2009, and determine azithromycin, ceftriaxone, ditamicin, tetracycline, ciprofloxacin, the minimum inhibitory concentration (MIC), and azithromycin resistance of the 318 strains of gonococcus by agar dilution method in 2008 and 2009. Neisseria gonorrhoeae was defined as a strain larger than or equal to the MIC value of azithromycin WHO P (azithromycin resistant strain) in each batch. 17 strains (5.3%) of Neisseria gonorrhoeae were resistant to azithromycin in Neisseria gonorrhoeae.
The second part is NG-MAST genotyping of azithromycin resistant Neisseria gonorrhoeae.
This part aims to understand the evolutionary relationship between the genotypes and strains of azithromycin resistant gonococci in Nanjing and Chongqing. 17 strains of azithromycin resistant Neisseria gonorrhoeae detected in the first part of NG-MAST genotyping and 11 NG-MAST genotypes in.17 resistant gonorrhoeae resistant.17 strains were analyzed by Mega software, of which 5 species were found. The genotypes (ST) with 6 strains of bacteria (MIC64mg/L) with the same genotype ST1866. genotype ST3367 and 4 newly registered genotypes were closely related to the genotype ST3356 of the most bacteria number, which may be the same source strain on the short transmission chain.
The third part is penA, porB and mtrR gene polymorphisms of ceftriaxone hypersensitivity Neisseria gonorrhoeae.
The purpose of this part is to understand the effect of penA, porB, and mtrR gene polymorphism on the sensitivity decline of gonococcus to ceftriaxone. 17 strains of ceftriaxone and 4 ceftriaxone sensitive strains detected in the first part were selected for penA, porB, mtrR gene sequencing and penA gene encoding of gonococci of.21 strain of.21 strain of.21 strain of NG-MAST White 2 (PBP2) found 9 amino acid structure patterns, 2 of which were not reported. There were 8 ceftriaxone low sensitive strains, 4 strains of ceftriaxone PBP2, no mosaic structure model (X) PBP2., 18 strains of gonococcus containing porB1b gene (encoded PorB1b protein), I218M, M257T/M257R and G25 PorB1b in PorB1b 9V amino acid replacement in the ceftriaxone low sensitive strain showed the presence of A39T or G45D or H105Y amino acid replacement in the 1mtrR gene encoding.21 strain of gonococcus, and A39T amino acid replacement only appeared in 3 ceftriaxone low sensitive strains. G45D or H105Y amino acid replacement appeared in the ceftriaxone low sensitive strain and the ceftriaxone sensitive strain. There are 13 NG-MAST genotypes in the hypersensitivity strain of triaxone, 3 of which are newly registered genotypes.PENa, porB, and mtrR gene polymorphisms may play a role in the decrease of ceftriaxone sensitivity.

【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2011
【分類號(hào)】：R759.2

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