發(fā)布時(shí)間：2018-05-19 20:28

  本文選題：非典型 + 多重耐藥　； 參考：《浙江大學(xué)》2015年博士論文

【摘要】：通過對我國大陸地區(qū)2003-2013年收集的1719株福氏志賀菌流行分布的回顧,可以看出,這11年間福氏志賀菌的流行以2a為主,其次是2v、lb、Y variant、3a、4s、4y, lc、6、4a、5b和3b。值得注意的是,福氏志賀菌可通過不斷變換血清型的方式長期流行,而非典型福氏志賀菌的流行對我國傳染病的監(jiān)測以及防控更是極大的挑戰(zhàn)。目前對非典型福氏志賀菌的相關(guān)研究較為匱乏,本研究旨在通過對非典型福氏志賀菌的表型和遺傳多態(tài)性研究深入了解其生物學(xué)特性、進(jìn)化關(guān)系和流行特征,為菌痢防控策略的制定奠定堅(jiān)實(shí)的基礎(chǔ)。 生化實(shí)驗(yàn)結(jié)果表明,149株非典型福氏志賀菌(F2v、Flc、F4y、F4s、F1b)分解葡萄糖；對甘露醇,蔗糖,蜜二糖等的利用因不同亞型而異。值得注意的是,血清型為4y和4s的部分菌株可以產(chǎn)生吲哚。藥敏實(shí)驗(yàn)結(jié)果表明,多重耐藥菌的比例高達(dá)92.6%,另外,通過對各血清型不同時(shí)間和地區(qū)的耐藥譜比較,我們發(fā)現(xiàn),F2v對頭孢和喹諾酮類藥物的耐藥率在2009年之后有了顯著地增長；而云南地區(qū)Flb的耐藥率比新疆地區(qū)高很多,這表明,同一血清型的耐藥率隨空間和時(shí)間都會有顯著改變,這提示我們應(yīng)持續(xù)地進(jìn)行耐藥性監(jiān)測,特別是一線用藥頭孢類藥物和喹諾酮類藥物的敏感性監(jiān)測,以便更好地指導(dǎo)臨床用藥。在耐頭孢類的54株志賀菌中,檢測到的耐藥基因有blaoTEM1, blaOXA1, blaCTX-M-14, blaCTM-M-3,blaCTC-M-79, intll及其攜帶的基因盒blaOTX-30+aadA1與aacA4+cmlA1, intI2及其攜帶的基因盒dfrA1+satl+aadA1。在28株耐喹諾酮類藥物的菌株中,所有菌株的ParC都發(fā)生了Ser80Ile突變；GyrA均有His211Tyr和Ser83Leu位點(diǎn)突變,部分菌株還有Asp87Asn/Gly突變。含有Asp87Asn突變的2株菌不僅對諾氟沙星耐藥,還對左氧氟沙星耐藥,因此我們推測,GyrA中Asp87Asn突變,可能介導(dǎo)對喹諾酮類藥物高水平的耐藥。另外,24株菌中檢測到aac(6')-Ib-cr基因,2株菌檢測到qnrSl基因。 本研究結(jié)合了3種分子分型方法MLST、PFGE和MLVA對149株菌進(jìn)行遺傳多態(tài)性分析,結(jié)果表明,所有的Flb和F1c菌株分別具有相同的序列型,ST104和ST100; Flc菌株有ST104和ST100兩種序列型；F4s菌株有ST99和ST100兩種序列型；F4y菌株有ST99、ST104、ST107和ST108四種序列型。所有菌株中,流行最多的序列型為ST100其次是ST104、ST99、ST108、ST107和ST105。ST100為優(yōu)勢的ST值,它與ST86的親緣關(guān)系最近,ST104次之。ST107與ST99和ST108都只有一個(gè)位點(diǎn)的差異。F2v作為一個(gè)新的亞型,它與F2a和F2b的親緣關(guān)系比較近；初步證明F2v是由F2a以及F2b進(jìn)化而來。Flc、F4s、F4y遺傳多態(tài)性明顯,其進(jìn)化可能來源于多個(gè)克隆系�？偟目磥�,MLVA方法的分辨率與PFGE分型方法的分辨率基本一致,比MLST分型方法分辨率高,三者結(jié)合起來可有效地應(yīng)用于細(xì)菌性痢疾暴發(fā)的溯源分析,為菌痢的防控提供良好的技術(shù)支持。
[Abstract]:Through a review of the distribution of 1719 strains of Shigella flexneri collected in 2003-2013 years in the mainland of China, we can see that the prevalence of Shigella flexneri was dominated by 2a in the last 11 years, followed by 2V, LB, Y variant, 3a, 4S, 4Y, LC, 6,4a, 5b and 3b., and it is worth noting that Shigella flexneri can be popular by constantly changing serotypes, and SARS. The epidemic of Shigella flexneri is a great challenge to the monitoring and control of infectious diseases in China. At present, the research on the atypical Shigella flexneri is scarce. The aim of this study is to understand the biological characteristics, evolution and epidemic characteristics through the study of the phenotype and genetic polymorphism of the atypical Shigella flexigella. The formulation of prevention and control strategies lays a solid foundation.
The results of biochemical experiments showed that 149 atypical Shigella flexneri (F2v, Flc, F4y, F4s, F1b) decomposed glucose, and the utilization of mannitol, sucrose and honey two sugar varied with different subtypes. It is worth noting that some strains of serotype 4Y and 4S can produce indoles. The results of drug sensitivity test showed that the proportion of multidrug resistant bacteria was up to 92.6%, in addition, By comparing the drug resistance spectrum of different serotypes and regions, we found that the resistance rate of F2v to cephalosporins and quinolones increased significantly after 2009, while the resistance rate of Flb in Yunnan was much higher than that in Xinjiang, which indicates that the rate of resistance to the same serotype changes significantly with space and time. We should continue to conduct drug resistance monitoring, especially the sensitivity monitoring of first line cephalosporins and quinolones, in order to better guide clinical use. In the 54 strains of Shigella resistant cephalosporins, the detected resistance genes are blaoTEM1, blaOXA1, blaCTX-M-14, blaCTM-M-3, blaCTC-M-79, intll and the genes they carry. Box blaOTX-30+aadA1 and aacA4+cmlA1, intI2 and its carrying gene box dfrA1+satl+aadA1. in 28 strains resistant to quinolones have Ser80Ile mutation in all strains; GyrA has His211Tyr and Ser83Leu site mutations, some strains and Asp87Asn/Gly mutations. 2 strains containing Asp87Asn mutation not only to norfloxacin. Star resistance and resistance to levofloxacin. Therefore, we speculate that Asp87Asn mutation in GyrA may mediate the high level of quinolone drug resistance. In addition, the AAC (6') -Ib-cr gene is detected in 24 strains, and 2 strains detect the qnrSl gene.
The genetic polymorphisms of 149 strains of MLST, PFGE and MLVA were analyzed in this study. The results showed that all Flb and F1c strains had the same sequence type, ST104 and ST100, and Flc strains had two sequences of ST104 and ST100, and F4s strains had ST99 and two sequence types. 8 of the four sequence types. Among all the strains, the most popular sequence type is ST100 followed by ST104, ST99, ST108, ST107 and ST105.ST100 as the dominant ST value. It is closest to ST86, and the difference between ST104 second.ST107 and ST99 and ST108 is a new subtype. It is proved that F2v has evolved from F2a and F2b to.Flc, F4s, F4y genetic polymorphism, and its evolution may come from multiple clone lines. In general, the resolution of MLVA method is basically consistent with the resolution of PFGE typing, which is higher than that of the MLST typing method. The combination of the three can be effectively applied to the traceability analysis of bacillary dysentery outbreak. It provides good technical support for the prevention and control of bacillary dysentery.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2015
【分類號】：R446.5

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