大腸埃希菌和肺炎克雷伯菌16S rRNA甲基化酶基因的篩選及轉(zhuǎn)移機制研究
發(fā)布時間：2018-07-16 20:33
【摘要】：研究背景 大腸埃希菌和肺炎克雷伯菌是臨床分離的常見病原菌,主要可以引起呼吸道感染、泌尿道感染、敗血癥、化膿性感染等,是引起醫(yī)院感染的重要病原菌,是臨床抗感染治療和醫(yī)院感染控制的主要對象。隨著抗菌藥物在臨床上的廣泛應(yīng)用,多重耐藥的大腸埃希菌和肺炎克雷伯菌引起的感染不斷增多,給臨床抗感染治療和醫(yī)院感染控制造成困難。特別是大腸埃希菌和肺炎克雷伯菌產(chǎn)生超廣譜β內(nèi)酰胺酶(Extended-spectrumβlactamases, ESBLs)后,造成對青霉素類、頭孢菌素類以及單環(huán)類抗菌藥物耐藥。除ESBLs外,大腸埃希菌和肺炎克雷伯菌還可產(chǎn)生質(zhì)粒介導(dǎo)的AmpC酶,導(dǎo)致耐藥性更加嚴(yán)重。近年來,在大腸埃希菌和肺炎克雷伯菌中還發(fā)現(xiàn)碳青霉烯酶,主要包括KPC酶和金屬酶,該類酶可以水解包括碳青霉烯類藥物在內(nèi)的所有β內(nèi)酰胺類抗菌藥物。氨基糖苷類抗生素由于具有耳和腎毒性,在臨床上的應(yīng)用受到一定的限制,但由于氨基糖苷類抗生素對銅綠假單胞菌、肺炎克雷伯菌、大腸埃希菌等常見革蘭陰性桿菌的抗生素后效應(yīng)較長,仍然被用于治療需氧革蘭陰性桿菌所致的嚴(yán)重感染。單獨使用氨基糖苷類抗生素治療時可能療效不佳,常需聯(lián)合應(yīng)用其他對革蘭陰性桿菌具有強大抗菌活性的抗菌藥物,如第三代頭孢菌素及氟喹諾酮類藥物等。細(xì)菌由于可以產(chǎn)生氨基糖苷類藥物鈍化酶,如N-乙酰基轉(zhuǎn)移酶、O-磷酸轉(zhuǎn)移酶及O-腺苷轉(zhuǎn)移酶,導(dǎo)致對氨基糖苷類藥物產(chǎn)生耐藥,這些修飾酶存在于質(zhì)�；蛉旧w上。這些修飾酶通常只作用一種或幾種結(jié)構(gòu)類似的氨基糖苷類抗生素,不能滅活所有的氨基糖苷類抗生素。 近年來,在革蘭陰性桿菌臨床分離株中發(fā)現(xiàn)一類質(zhì)粒介導(dǎo)的16S rRNA甲基化酶,該酶能夠保護細(xì)菌的30S核糖體16S rRNA不被氨基糖苷類抗生素結(jié)合,造成對包括阿貝卡星在內(nèi)的臨床上常用的氨基糖苷類抗生素耐藥,并且為高水平耐藥。自2003年發(fā)現(xiàn)首個16S rRNA甲基化酶ArmA以來,到目前為止,在革蘭陰性桿菌臨床分離株中已發(fā)現(xiàn)ArmA、RmtA、RmtB、RmtC、RmtD和NpmA6種16S rRNA甲基化酶,編碼這些酶的結(jié)構(gòu)基因通過質(zhì)粒在不同的菌株之間播散。最近,在牛體內(nèi)分離的大腸埃希菌中又發(fā)現(xiàn)了16S rRNA甲基化酶RmtE,但在臨床分離株中沒有發(fā)現(xiàn)RmtE。據(jù)報道,世界許多地方發(fā)生由產(chǎn)16S rRNA甲基化酶菌株造成的感染。我國有關(guān)產(chǎn)16S rRNA甲基化酶菌株引起感染的流行病學(xué)數(shù)據(jù)不夠全面,特別是16S rRNA甲基化酶基因的轉(zhuǎn)移機制研究不夠深入本研究擬對分離自溫州醫(yī)學(xué)院附屬第一醫(yī)院的大腸埃希菌和肺炎克雷伯菌臨床分離株的16S rRNA甲基化酶基因進行篩選,并對16S rRNA甲基化酶基因轉(zhuǎn)移的機制進行研究。 第一部分大腸埃希菌和肺炎克雷伯菌16S rRNA甲基化酶基因的篩選 收集溫州醫(yī)學(xué)院附屬第一醫(yī)院2006年1月至2007年9月臨床分離的337株肺炎克雷伯菌以及2006年1月至2008年7月臨床分離的680株大腸埃希菌,所有菌株均為非重復(fù)株。利用全自動微生物分析儀進行菌種鑒定和藥敏試驗,篩選對慶大霉素(GEN)、妥布霉素(TOB)和阿米卡星(AMK)任一藥物耐藥的菌株作為被測菌株。共篩選出64株肺炎克雷伯菌至少耐一種上述氨基糖苷類藥物,被選為測試菌株。337株肺炎克雷伯菌對GEN、TOB和AMK的耐藥率分別為19.0%(64/337)、16.3%(55/337)和8.3%(28/337)；28株菌同時耐GEN、TOB和AMK,所有28株耐AMK的肺炎克雷伯菌同時耐TOB和GEN。365株大腸埃希菌至少耐一種上述氨基糖苷類藥物,44株同時對GEN、AMK和TOB耐藥,被挑選為被測菌株。680株大腸埃希菌對GEN、TOB和AMK的耐藥率分別為52.5%(357/680)、50.9%(346/680)和6.5%(44/680)。所有耐AMK的大腸埃希菌同時耐GEN和TOB。AMK對大腸埃希菌和肺炎克雷伯菌臨床分離株的體外抗菌活性強。 經(jīng)PCR檢測和DNA測序證實,21株肺炎克雷伯菌16S rRNA甲基化酶基因陽性,陽性率為6.2%(21/337),其中3株為armA陽性、13株為rmtB陽性及5株為armA和rmlB同時陽性。16S rRNA甲基化酶基因在AMK耐藥株、TOB耐藥株和GEN耐藥株中的檢出率分別為75.0%(21/28)、38.2%(21/55)和32.8%(21/64)。37株大腸埃希菌16S rRNA甲基化酶基因陽性,總的陽性率為5.4%(37/680),其中36株為rmtB陽性,l株為armA陽性。所有被測菌株rmtA、rmtC、rmtD和npmA為陰性。所有16S rRNA甲基化酶基因陽性株對GEN、TOB和AMK高度耐藥(MIC256mg/L)。19株(90.5%,19/21)16S rRNA甲基化酶基因陽性肺炎克雷伯菌株產(chǎn)ESBLs,經(jīng)PCR檢測和DNA測序證實,21株、15株和19株分別為blaTEM、blasHv和blaCTX-M基因陽性。所有blaTEM為blaTEM-1,blasHv主要為blaSHv-12,19株blaCTX-M陽性株分別為13株blaCTX-M-14陽性和6株blaCTX-M-15陽性。29株(78.4%,29/37)16S rRNA甲基化酶基因陽性大腸埃希菌株產(chǎn)ESBLs,經(jīng)PCR檢測和DNA測序證實,37株全部為blaTEM陽性,經(jīng)測序全部為blaTEM-1。29株產(chǎn)ESBLs株和2株ESBLs陰性株blaCTX-M基因為陽性,主要為blaCTX-M-14和blaCTX-M-15。所有16SrRNA甲基化酶基因陽性的肺炎克雷伯菌和大腸埃希菌株I類整合酶基因陽性。 16S rRNA甲基化酶基因已經(jīng)在溫州地區(qū)分離的大腸埃希菌和肺炎克雷伯菌臨床分離株中播散,基因型為rmtB和armA,且以rmtB為主；首次發(fā)現(xiàn)rmtB和armA共同存在于同一菌株中；16S rRNA甲基化酶基因陽性株對GEN、TOB和AMK高度耐藥,16S rRNA甲基化酶基因通常與ESBL基因和I類整合酶基因共同存在于同一菌株中,造成多重耐藥。 第二部分16S rRNA甲基化酶基因轉(zhuǎn)移機制研究 以16S rRNA甲基化酶基因陽性的大腸埃希菌和肺炎克雷伯菌株作為供體菌,以疊氮鈉耐藥的大腸埃希菌J53為受體菌進行接合試驗。13株(61.9%,13/21)肺炎克雷伯菌通過接合試驗成功地將攜帶16S rRNA甲基化酶基因質(zhì)粒傳遞給受體菌,其中2株為armA陽性株、7株為rrntB陽性株及4株為armA和rmtB同時陽性株,但5株armA和rmtB同時陽性株的接合子只有rmtB陽性。經(jīng)反復(fù)試驗,只有4株(10.8%,4/37)rmtB陽性的大腸埃希菌株通過接合試驗成功地將攜帶16S rRNA甲基化酶基因質(zhì)粒傳遞給受體菌。所有接合子對GEN、TOB和AMK高度耐藥,且I類整合酶基因全部為陽性,ESBL基因型與供菌相同。利用質(zhì)粒中量抽取試劑盒提取非接合菌株的質(zhì)粒,經(jīng)轉(zhuǎn)化試驗把耐藥質(zhì)粒轉(zhuǎn)入大腸埃希菌DH5a獲得轉(zhuǎn)化子,所有轉(zhuǎn)化子對GEN、TOB和AMK高度耐藥,且I類整合酶基因全部為陽性,所攜帶的ESBL基因型與供菌相同。 利用DNA分子雜交試驗對5株armA和rmtB同時陽性的肺炎克雷伯菌和其接合子的質(zhì)粒進行DNA雜交,發(fā)現(xiàn)rmtB位于一個約75Kb的質(zhì)粒上,而armA可能位于染色體上。利用分子雜交試驗對一株rmtB陽性和另一株armA陽性的大腸埃希菌及其轉(zhuǎn)化子的質(zhì)粒進行DNA雜交,發(fā)現(xiàn)大腸埃希菌中的rmtB和armA位于一個約54Kb的質(zhì)粒上。利用Walking測序法獲得肺炎克雷伯菌rmtB基因周圍序列約11Kb大小的片段,發(fā)現(xiàn)緊鄰rmtB基因的上游存在一個Tn3轉(zhuǎn)座子序列,rmtB基因存在兩個插入序列IS26之間,在轉(zhuǎn)座酶tnpA基因的下游存在一個編碼與接合功能有關(guān)的traI基因。大腸埃希菌中的rmtB的上游與肺炎克雷伯菌中的rmtB基因上游相同,但下游存在一個喹諾酮類藥物的外排泵基因qepA。大腸埃希菌和肺炎克雷伯菌中的armA基因的上游存在兩個轉(zhuǎn)座酶基因,分別為轉(zhuǎn)座酶基因tnpA和tnpU，，在轉(zhuǎn)座酶基因tnpU的上游存在一個LSCR1插入序列；在armA的下游存在一個轉(zhuǎn)座酶基因tnpD。 存在于肺炎克雷伯菌中的rmtB基因通常與ESBL基因和I類整合子共同位于可轉(zhuǎn)移的質(zhì)粒上,通過質(zhì)粒在不同的菌株之間轉(zhuǎn)移。5株armA和rmtB同時陽性株的armA可能位于染色體上,其余菌株的armA位于質(zhì)粒上。存在于大腸埃希菌中的armA和rmtB基因通常與ESBL基因和I類整合子共同位于非接合性的質(zhì)粒上。armA和rmtB周圍存在插入序列以及轉(zhuǎn)座酶基因,可能通過轉(zhuǎn)座子發(fā)生轉(zhuǎn)移。存在于肺炎克雷伯菌中的攜帶rmtB的質(zhì)�？梢酝ㄟ^接合發(fā)生轉(zhuǎn)移的原因為rmtB下游存在一個與接合相關(guān)的traI基因,而存在大腸埃希菌中的rmtB基因下游缺乏traI基因,是質(zhì)粒不能通過接合發(fā)生轉(zhuǎn)移的原因。大腸埃希菌中的rmtB基因下游含有qepA基因,是導(dǎo)致rmtB基因陽性株對環(huán)丙沙星和左氧氟沙星同時耐藥的原因。 第三部分16S rRNA甲基化酶基因陽性株同源性分析 利用PFGE對21株16S rRNA甲基化酶基因陽性的肺炎克雷伯菌和37株16SrRNA甲基化酶基因陽性的大腸埃希菌進行了同源性分析。21株肺炎克雷伯菌共分成14個PFGE型,主要為A型和I型；5株屬于A型,其中4株分離自ICU和1株分離自神經(jīng)外科的rmtB陽性株；4株屬于I型,其中3株分離自胸外科和1株分離自泌尿外科,4株菌為armA和rmtB同時陽性,其余都為每株屬于單-的PFGE型并分布在不同的科室。37株16S rRNA甲基化酶基因陽性的大腸埃希菌共分成19個PFGE型,其中H型共12株,A和N型各3株,G、I和P型各2株,其余型各1株。同一PEGE型菌株存在于多個科室,而同一科室存在多個PFGE型。 攜帶16S rRNA甲基化酶基因的肺炎克雷伯菌和大腸埃希菌都存在克隆株的播散,但大部分菌株分散在遺傳上不相關(guān)的克隆中；同一個克隆在不同病房中造成感染的播散；同一病房存在多個散在的克��；rmtB和armA基因陽性株可通過克隆株方式進行播散,也可通過水平方式進行傳播。 小結(jié) 綜上所述,本研究的結(jié)論主要有以下幾點：1.阿米卡星對大腸埃希菌和肺炎克雷伯菌臨床分離株的體外抗菌活性非常強,是篩選16S rRNA甲基化酶基因的理想藥物；2.溫州地區(qū)臨床分離的大腸埃希菌和肺炎克雷伯菌的16S rRNA甲基化酶基因陽性率較高,且rmtB基因的陽性率高于armA的陽性率,與國外的報道相反；3.首次發(fā)現(xiàn)rmtB和armA基因同時位于同一菌株中；4.在大腸埃希菌中,16S rRNA甲基化酶基因通常與ESBL基因和I類整合子同時位于一個非接合性的質(zhì)粒上。在肺炎克雷伯菌中,16S rRNA甲基化酶基因通常與ESBL基因和I類整合子同時位于一個可自我轉(zhuǎn)移的接合性質(zhì)粒上；5.rmtB和armA基因常位于插入序列之間,通過轉(zhuǎn)座子進行轉(zhuǎn)移。存在于大腸埃希菌和肺炎克雷伯菌臨床分離中的armA基因周圍序列相同,armA的來源及轉(zhuǎn)移機制可能相同,而存在于兩種菌中的rmtB基因周圍序列不同,兩種菌rmtB的來源、轉(zhuǎn)移機制和耐藥表型可能不同。6.16S rRNA甲基化酶基因陽性的大腸埃希菌和肺炎克雷伯菌可通過克隆株的方式進行播散,也可通過水平方式進行傳播。
[Abstract]:Background of the study
Escherichia coli and Klebsiella pneumoniae are common pathogens of clinical isolation , which can cause respiratory tract infection , urinary tract infection , septicemia , suppurative infection , etc .
In recent years , a kind of plasmid - mediated 16S rRNA methylase has been found in the clinical isolates of Gram - negative bacilli , which can protect the 16S rRNA of the bacterium ' s 30S ribosomal 16S rRNA from aminoglycosides , and it is resistant to high level of resistance . In recent years , the 16S rRNA methylase RmtE has been found in the clinical isolates of Gram - negative bacilli .
Screening of 16S rRNA methylase genes of Escherichia coli and Klebsiella pneumoniae in the first part
The clinical isolates from January 2006 to September 2007 were collected from the First Affiliated Hospital of Wenzhou Medical College from January 2006 to September 2007 . All the strains were non - repeated strains .
All 28 strains of Escherichia coli resistant to AMK were resistant to both GEN , AMK and TOB at the same time , and the resistant rates were 59.5 % ( 357 / 680 ) , 50.9 % ( 346 / 680 ) and 6.5 % ( 44 / 680 ) respectively .
The results of PCR and DNA sequencing showed that the positive rate of 16S rRNA methylase gene of 21 strains of Klebsiella pneumoniae was 6.2 % ( 21 / 337 ) , among which 3 strains were armA positive , 13 strains were rmtB positive and 5 strains were both armA and rmlB .
The 16S rRNA methylase gene was disseminated in the clinical isolates of Escherichia coli and Klebsiella pneumoniae isolated in Wenzhou region . The genotypes were rmtB and armA , and rmtB was dominant .
It was found that rmtB and armA were present in the same strain for the first time .
The 16S rRNA methylase gene positive strain is highly resistant to GEN , TOB and AMK . The 16S rRNA methylase gene is commonly present in the same strain as the ESBL gene and the class I integration enzyme gene , resulting in multiple resistance .
Study on the mechanism of gene transfer of 16S rRNA methylase in the second part
The results showed that only 4 ( 10.8 % , 4 / 37 ) rmtB - positive strains were positive to GEN , TOB and AMK . All transformants were highly resistant to GEN , TOB and AMK . All transformants were highly resistant to GEN , TOB and AMK . All transformants were positive for GEN , TOB and AMK .
Using molecular hybridization , we found that rmtB and armA were located in a plasmid of about 54Kb .
Downstream of armA , there is a transpositional enzyme gene tnpD .
The rmtB gene , which is present in Klebsiella pneumoniae , is usually co - located with ESBL gene and I - type integron in a transferable plasmid . The armA and rmtB genes present in Escherichia coli may be located on the chromosome , and the armA of the other strains is located on the plasmid . The plasmid carrying the rmtB present in Escherichia coli can be transferred by conjugation . The downstream of the rmtB gene in Escherichia coli can be transferred by conjugation . The downstream of the rmtB gene in Escherichia coli contains the qepA gene , which is the cause of the simultaneous resistance of the rmtB gene positive strain to ciprofloxacin and levofloxacin .
Homology analysis of the third partial 16S rRNA methylase gene positive strain
21 strains of Klebsiella pneumoniae and 37 strains of 16SrRNA methylase were analyzed by PFGE . 21 strains of Klebsiella pneumoniae were divided into 14 PFGE types , mainly A and I ;
5 strains belonged to type A , among which 4 were isolated from ICU and 1 isolated from the rmtB positive strain of neurosurgery .
Four strains belong to type I , among which 3 strains isolated from thoracic surgery and 1 isolated from urology , 4 strains were both armA and rmtB , the others were PFGE type belonging to single - PFGE type and distributed in different departments .
The strains of Klebsiella pneumoniae and Escherichia coli carrying 16S rRNA methylase gene all have the spreading of clonal strains , but most of the strains are dispersed in genetically unrelated clones ;
the same clone causes the spread of infection in different wards ;
a plurality of scattered clones exist in the same ward ;
The rmtB and armA gene - positive strains can be disseminated by cloning , and can also be propagated horizontally .
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In conclusion , the conclusions of this study are as follows : 1 . The in vitro antibacterial activity of amikaine to Escherichia coli and Klebsiella pneumoniae clinical isolates is very strong , which is the ideal drug for screening 16S rRNA methylase gene ;
2 . The positive rate of 16S rRNA methylase gene of Escherichia coli and Klebsiella pneumoniae was higher in Wenzhou region , and the positive rate of rmtB gene was higher than that of armA .
3 . The rmtB and armA genes were found in the same strain for the first time .
4 . In Escherichia coli , the 16S rRNA methylase gene is usually located on a non - binding plasmid with the ESBL gene and the I - type integron . In Klebsiella pneumoniae , the 16S rRNA methylase gene is usually located on a self - transferable bond particle at the same time as the ESBL gene and the I - type integron ;
5 . The rmtB and armA genes are often located between the insertion sequences and transferred through the transposon . The source and transfer mechanism of armA are the same around the armA gene in the clinical isolates of Escherichia coli and Klebsiella pneumoniae . The origin , transfer mechanism and drug resistant phenotype of both strains may be different . 6 . The E . coli and Klebsiella pneumoniae positive for 16S rRNA methylase gene may be disseminated by cloning , and can also be propagated horizontally .
【學(xué)位授予單位】：復(fù)旦大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2011
【分類號】：R378
本文編號：2127594
[Abstract]:Background of the study
Escherichia coli and Klebsiella pneumoniae are common pathogens of clinical isolation , which can cause respiratory tract infection , urinary tract infection , septicemia , suppurative infection , etc .
In recent years , a kind of plasmid - mediated 16S rRNA methylase has been found in the clinical isolates of Gram - negative bacilli , which can protect the 16S rRNA of the bacterium ' s 30S ribosomal 16S rRNA from aminoglycosides , and it is resistant to high level of resistance . In recent years , the 16S rRNA methylase RmtE has been found in the clinical isolates of Gram - negative bacilli .
Screening of 16S rRNA methylase genes of Escherichia coli and Klebsiella pneumoniae in the first part
The clinical isolates from January 2006 to September 2007 were collected from the First Affiliated Hospital of Wenzhou Medical College from January 2006 to September 2007 . All the strains were non - repeated strains .
All 28 strains of Escherichia coli resistant to AMK were resistant to both GEN , AMK and TOB at the same time , and the resistant rates were 59.5 % ( 357 / 680 ) , 50.9 % ( 346 / 680 ) and 6.5 % ( 44 / 680 ) respectively .
The results of PCR and DNA sequencing showed that the positive rate of 16S rRNA methylase gene of 21 strains of Klebsiella pneumoniae was 6.2 % ( 21 / 337 ) , among which 3 strains were armA positive , 13 strains were rmtB positive and 5 strains were both armA and rmlB .
The 16S rRNA methylase gene was disseminated in the clinical isolates of Escherichia coli and Klebsiella pneumoniae isolated in Wenzhou region . The genotypes were rmtB and armA , and rmtB was dominant .
It was found that rmtB and armA were present in the same strain for the first time .
The 16S rRNA methylase gene positive strain is highly resistant to GEN , TOB and AMK . The 16S rRNA methylase gene is commonly present in the same strain as the ESBL gene and the class I integration enzyme gene , resulting in multiple resistance .
Study on the mechanism of gene transfer of 16S rRNA methylase in the second part
The results showed that only 4 ( 10.8 % , 4 / 37 ) rmtB - positive strains were positive to GEN , TOB and AMK . All transformants were highly resistant to GEN , TOB and AMK . All transformants were highly resistant to GEN , TOB and AMK . All transformants were positive for GEN , TOB and AMK .
Using molecular hybridization , we found that rmtB and armA were located in a plasmid of about 54Kb .
Downstream of armA , there is a transpositional enzyme gene tnpD .
The rmtB gene , which is present in Klebsiella pneumoniae , is usually co - located with ESBL gene and I - type integron in a transferable plasmid . The armA and rmtB genes present in Escherichia coli may be located on the chromosome , and the armA of the other strains is located on the plasmid . The plasmid carrying the rmtB present in Escherichia coli can be transferred by conjugation . The downstream of the rmtB gene in Escherichia coli can be transferred by conjugation . The downstream of the rmtB gene in Escherichia coli contains the qepA gene , which is the cause of the simultaneous resistance of the rmtB gene positive strain to ciprofloxacin and levofloxacin .
Homology analysis of the third partial 16S rRNA methylase gene positive strain
21 strains of Klebsiella pneumoniae and 37 strains of 16SrRNA methylase were analyzed by PFGE . 21 strains of Klebsiella pneumoniae were divided into 14 PFGE types , mainly A and I ;
5 strains belonged to type A , among which 4 were isolated from ICU and 1 isolated from the rmtB positive strain of neurosurgery .
Four strains belong to type I , among which 3 strains isolated from thoracic surgery and 1 isolated from urology , 4 strains were both armA and rmtB , the others were PFGE type belonging to single - PFGE type and distributed in different departments .
The strains of Klebsiella pneumoniae and Escherichia coli carrying 16S rRNA methylase gene all have the spreading of clonal strains , but most of the strains are dispersed in genetically unrelated clones ;
the same clone causes the spread of infection in different wards ;
a plurality of scattered clones exist in the same ward ;
The rmtB and armA gene - positive strains can be disseminated by cloning , and can also be propagated horizontally .
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In conclusion , the conclusions of this study are as follows : 1 . The in vitro antibacterial activity of amikaine to Escherichia coli and Klebsiella pneumoniae clinical isolates is very strong , which is the ideal drug for screening 16S rRNA methylase gene ;
2 . The positive rate of 16S rRNA methylase gene of Escherichia coli and Klebsiella pneumoniae was higher in Wenzhou region , and the positive rate of rmtB gene was higher than that of armA .
3 . The rmtB and armA genes were found in the same strain for the first time .
4 . In Escherichia coli , the 16S rRNA methylase gene is usually located on a non - binding plasmid with the ESBL gene and the I - type integron . In Klebsiella pneumoniae , the 16S rRNA methylase gene is usually located on a self - transferable bond particle at the same time as the ESBL gene and the I - type integron ;
5 . The rmtB and armA genes are often located between the insertion sequences and transferred through the transposon . The source and transfer mechanism of armA are the same around the armA gene in the clinical isolates of Escherichia coli and Klebsiella pneumoniae . The origin , transfer mechanism and drug resistant phenotype of both strains may be different . 6 . The E . coli and Klebsiella pneumoniae positive for 16S rRNA methylase gene may be disseminated by cloning , and can also be propagated horizontally .
【學(xué)位授予單位】：復(fù)旦大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2011
【分類號】：R378
【參考文獻】
相關(guān)期刊論文 前1條
1 楊啟文;徐英春;陳民鈞;胡云建;倪語星;孫景勇;俞云松;孔海深;何林;吳偉元;葉惠芬;楊銀梅;朱蓮娜;郭世輝;季萍;朱震宏;任健康;張利俠;孫自鏞;朱旭慧;童明慶;趙旺勝;梅亞寧;劉勇;張智潔;段瓊;李丹;劉蓬蓬;王晶;韓麗霞;王輝;謝秀麗;;2005年中國十五家教學(xué)醫(yī)院院內(nèi)獲得革蘭陰性病原菌耐藥性分析[J];中華醫(yī)學(xué)雜志;2007年39期
本文編號：2127594
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