本文選題：多重耐藥 + 鮑曼不動(dòng)桿菌　； 參考：《中國(guó)人民解放軍軍醫(yī)進(jìn)修學(xué)院》2011年博士論文

【摘要】：背景： 多重耐藥鮑曼不動(dòng)桿菌是引起醫(yī)院感染的重要條件致病菌,給院內(nèi)感染防控和治療提出了嚴(yán)峻的挑戰(zhàn)。本文報(bào)道了多重耐藥鮑曼不動(dòng)桿菌臨床分離株的基因組多態(tài)性,以及代表性流行克隆株AB07104、AB0868和AB0715的全基因組序列,并進(jìn)行了耐藥基因組的初步分析。 方法： 采用多重PCR方法快速鑒定多重耐藥鮑曼不動(dòng)桿菌；分別應(yīng)用DiversiLab微生物基因組分型系統(tǒng)、基于序列型多重PCR方法和MLST分型技術(shù)對(duì)194株多重耐藥鮑曼不動(dòng)桿菌的分子流行特征進(jìn)行分析,將上述3種基因分型技術(shù)進(jìn)行合理組合,建立了多重耐藥鮑曼不動(dòng)桿菌的分子溯源系統(tǒng)；利用在線細(xì)菌基因組注釋系統(tǒng)BASys對(duì)3株菌(AB07104、AB0868和AB0715)的全基因組序列進(jìn)行注釋,確定了編碼基因,在此基礎(chǔ)上,綜合利用相關(guān)的分子生物信息學(xué)分析軟件,在全基因組水平掃描所有與耐藥相關(guān)的基因元件,從耐藥基因組的角度探討了鮑曼不動(dòng)桿菌多重耐藥性的形成機(jī)制。 結(jié)果： 194菌株中均攜帶有blaOXA-51-like基因,對(duì)鮑曼不動(dòng)桿菌的鑒定率為100%,全部實(shí)驗(yàn)菌株具有9種耐藥基因組合,其中以blaOXA-51-like+blaOXA-23-like+intI組合為主(n=139,71.65%),而blaOXA-23-like、blaOXA-24-like、blaOXA-58-like和intI的檢出率分別為76.29%、1.55%、1.55%和89.18%；多重耐藥鮑曼不動(dòng)桿菌主要流行克隆株MLST的等位基因譜為ST2(2-2-2-2-2-2-2),與英國(guó)流行克隆OXA-23 clone 1也具有相同的MLST等位基因譜,研究還發(fā)現(xiàn)了一個(gè)新的攜帶blaOXA-58-like基因的多重耐藥鮑曼不動(dòng)桿菌流行克隆ST23(Institute Pastuer MLST Scheme)/ST91(Bartual et al. MLST Scheme);多重耐藥鮑曼不動(dòng)桿菌全基因組具有非常豐富的插入序列ISAbal,位于blaOXA-23-like、ampC、sulⅡ等耐藥基因的上游,blaOXA-23-like基因的轉(zhuǎn)移載體為Tn2008；耐藥基因組不僅包含有豐富的特異性耐藥相關(guān)基因,同時(shí)也具有多拷貝的外排泵編碼基因、多重耐藥蛋白編碼基因、重金屬抗性相關(guān)基因、外膜蛋白編碼基因等,另外,還發(fā)現(xiàn)3株菌gyrA(Ser83Leu)和parC(Ser80Ile)基因的QRDR發(fā)生了突變,但未發(fā)現(xiàn)具有典型結(jié)構(gòu)的‘'AbaR型耐藥島”。 結(jié)論： 本研究解決了醫(yī)院感染監(jiān)測(cè)中多重耐藥鮑曼不動(dòng)桿菌的快速鑒定問(wèn)題,以及在臨床實(shí)驗(yàn)室如何合理應(yīng)用基因分型技術(shù)進(jìn)行主要流行克隆株溯源的難題；我國(guó)多重耐藥鮑曼不動(dòng)桿菌臨床分離株的主要流行克隆以歐洲克隆譜系Ⅱ?yàn)橹?不具有典型結(jié)構(gòu)的‘'AbaR型耐藥島”；通過(guò)在全基因組水平分析耐藥相關(guān)的基因元件,使我們對(duì)我國(guó)多重耐藥鮑曼不動(dòng)桿菌流行克隆株的“耐藥基因組”有了更加清晰的認(rèn)識(shí),為進(jìn)一步研究多重耐藥鮑曼不動(dòng)桿菌“組合式耐藥機(jī)制”奠定了基礎(chǔ)。
[Abstract]:Background: Acinetobacter baumannii multidrug resistance is an important condition of nosocomial infection, which poses a severe challenge to the prevention, control and treatment of nosocomial infection. This paper reports the genomic polymorphism of the clinical isolates of Acinetobacter baumannii and the complete genome sequences of AB07104, AB0868 and AB0715, and makes a preliminary analysis of the drug-resistant genome. Methods: The multidrug resistant Acinetobacter baumannii was quickly identified by multiplex PCR, and the genomic typing system of DiversiLab microbes was used. The molecular epidemiological characteristics of Acinetobacter baumannii were analyzed based on sequence multiple PCR method and MLST typing technique, and the three genotyping techniques were reasonably combined. The molecular traceability system of Acinetobacter baumannii with multidrug resistance was established, and the whole genome sequence of three strains of Acinetobacter baumannii AB07104, AB0868 and AB0715 were annotated by the online bacterial genome annotation system (BASys). The mechanism of multidrug resistance of Acinetobacter baumannii was discussed from the point of view of drug resistance genome by comprehensively scanning all the gene elements related to drug resistance at the whole genome level using the relevant molecular bioinformatics analysis software. Results: The identification rate of Acinetobacter baumannii was 100. All the strains had 9 combinations of drug resistance genes. The detection rates of blaOXA-23-like blaOXA-24-like blaOXA-58-like and intI were 76.295.55% and 89.18%, respectively. The allele profile of MLST, the main prevalent clone of Acinetobacter baumannii, was ST2O2-2-2-2-2-2-2-2-22G, which also had the same MLST allele profile as the British popular clone OXA-23 clone 1. A new multidrug resistant Acinetobacter baumannii clone ST23(Institute Pastuer MLST Scheme)/ST91(Bartual et alwas also found. The whole genome of Acinetobacter baumannii has a very rich insertion sequence, ISAbal. the transfer vector of the upstream of the resistant genes such as blaOXA-23-like ampcsul 鈪，

本文編號(hào)：1914591