同时产碳青霉烯酶NDM-1和NDM-5的猪源大肠埃希氏菌的鉴定及耐药性研究

doi:10.13560/j.cnki.biotech.bull.1985.2022-0073

摘要/Abstract

摘要：

为了解携带碳青霉烯酶NDM-1及其亚型在猪场的流行情况,对来自猪场产房仔猪腹泻病例分离鉴定的87株大肠杆菌进行了碳青霉烯酶NDM-1和NDM-5的耐药基因扩增及测序。从87株大肠杆菌中分离鉴定出一株同时携带碳青霉烯酶NDM-1和NDM-5的大肠埃希菌（Escherichia coli）,并命名为HN2106。为深入了解HN2106全基因组及其携带的质粒和耐药基因情况,对NH2106进行了16S rRNA菌种鉴定,bla_NDM耐药基因确认,全基因组测序,应用BLAST和MEGA软件对序列进行生物信息学分析、系统进化树分析。结果显示,该菌株含有7个质粒（plasmid A、plasmid B、plasmid C、plasmid D、plasmid E、plasmid F 和plasmid G）,3种类型,分别为Col、IncFII、IncQ1。同时携带NDM-1和NDM-5基因,属B族β-内酰胺酶,其中bla_NDM-1位于质粒pNDM-HN2106（plasmid C）上,bla_NDM-5位于质粒pNDM5-HN2106（plasmid B）上,分别介导bla_NDM-1和bla_NDM-5耐药基因,是耐药菌传播的重要载体。全基因组耐药基因预测HN2106同时还携带21种类型的抗生素耐药基因。对HN2106菌株进行了85种抗菌药物敏感性测试,结果显示,HN2106菌株对亚胺培南、青霉素G等均耐药,对磺胺甲恶唑、头孢美唑等敏感。研究结果表明,养殖场NDM-1耐药质粒是NDM-1及其亚型耐药基因的重要载体,对养殖产业健康养殖和公共卫生安全带来较大隐患和威胁,应加强抗菌药物的合理应用和感染的防控措施,重视细菌耐药性的监测工作,以期为临床耐药菌株感染的防治提供理论参考。

关键词: 碳青霉烯酶, NDM-1, NDM-5, 大肠埃希氏菌, 细菌耐药

Abstract:

In order to understand the prevalence of carbapenemase-carrying NDM-1 and its subtypes in pig farms,87 strains of Escherichia coli were isolated and identified from piglet diarrhea cases. Carbapenemase-resistant genes NDM-1 and NDM-5 were amplified and sequenced. An E. coli strain carrying both NDM-1 and NDM-5 was identified from 87 strains of E. coli and named HN2106. In order to further understand the whole genome of HN2106 and the plasmids and drug-resistant genes carried by HN2106,16S rRNA strain identification of NH2106 was conducted,bla_NDM drug-resistant gene was confirmed,and whole genome sequencing was performed. BLAST and MEGA software were used for bioinformatics analysis and phylogenetic tree analysis. The results showed that the strain contained 7 plasmids（plasmid A,plasmid B,plasmid C,plasmid D,plasmid E,plasmid F,and plasmid G）,in 3 types,were as Col,IncFII,and IncQ1. The strain simultaneously carried gene NDM-1 and NDM-5,they belonged to a β -lactamase of group B,in which bla_NDM-1 was located at plasmid pNDM5-HN2106（plasmid C）,bla_NDM-5 was located at plasmid pNDM5-HN2106（plasmid B）. They mediated bla_NDM-1 and bla_NDM-5 resistance genes,respectively,and were important vectors for the transmission of drug-resistant bacteria. The prediction of whole genome resistance gene demonstrated that HN2106 also carried 21 types of antibiotic resistance genes. The resistances of HN2106 strain to 85 antibiotics were tested,and the results showed that HN2106 was resistant to imipenem,penicillin G,et al.,as well as it was sensitive to sulfamethoxazole,cefmetazole,et al. The above results reveal that NDM-1 drug-resistant plasmid is an important vector of NDM-1 and its subtype resistance genes,which may bring great hidden dangers and threats to healthy breeding and public health safety in the breeding industry. In order to provide theoretical reference for the prevention and treatment of clinical drug-resistant bacterial infection,it is necessary to strengthen the rational application of antibacterial drugs and the prevention and control measures of infection,and pay more attentions to the monitoring of bacterial resistances.

Key words: carbapenase, NDM-1, NDM-5, Escherichia coli, bacterial drug resistance

李海利, 郎利敏, 张青娴, 游一, 朱文豪, 王治方, 张立宪, 王克领. 同时产碳青霉烯酶NDM-1和NDM-5的猪源大肠埃希氏菌的鉴定及耐药性研究[J]. 生物技术通报, 2022, 38(9): 106-115.

LI Hai-li, LANG Li-min, ZHANG Qing-xian, YOU Yi, ZHU Wen-hao, WANG Zhi-fang, ZHANG Li-xian, WANG Ke-ling. Identification and Drug Resistance of Escherichia coli Simultaneously Producing Carbapenemase NDM-1 and NDM-5[J]. Biotechnology Bulletin, 2022, 38(9): 106-115.

图/表 6

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引物Primers name	引物序列Primer sequence（5'-3'）	产物长度Amplicon size/bp	退火温度PCR annealing temperature/℃
NDM-5F	ATGGAATTGCCCAATATTATGCAC	480	58
NDM-5R	TCAGCGCAGCTTGTCGGC	480	58
NDM-1F	GGTTTGGCGATCTGGTTTTC	593	57
NDM-1R	CGGAATGGCTCATCACGATC	593	57

引物Primers name	引物序列Primer sequence（5'-3'）	产物长度Amplicon size/bp	退火温度PCR annealing temperature/℃
NDM-5F	ATGGAATTGCCCAATATTATGCAC	480	58
NDM-5R	TCAGCGCAGCTTGTCGGC	480	58
NDM-1F	GGTTTGGCGATCTGGTTTTC	593	57
NDM-1R	CGGAATGGCTCATCACGATC	593	57

抗生素Antibiotics	HN2106	抗生素Antibiotics	HN2106	抗生素Antibiotics	HN2106	抗生素Antibiotics	HN2106
亚胺培南Imipenem	R	头孢西丁Cefoxitin	R	庆大霉素Gentamicin	R	奈替米星Netilmicin	R
氨苄西林Ampicillin	R	头孢克洛Cefaclor	R	卡那霉素Kanamycin	R	诺氟沙星Norfloxacin	R
海他西林Hetacillin	R	头孢呋辛Cefuroxime	R	阿米卡星Amikacin	R	新霉素Neomycin	R
阿莫西林 Amoxicillin	R	头孢噻肟 Cefotaxime	R	链霉素 Streptomycin	R	羧苄西林 Carbenicillin	R
苯唑西林Oxacillin	R	头孢唑肟ceftizoxime	R	多西环素Doxycycline	R	哌拉西林Piperacillin	R
氯唑西林 Cloxacillin	R	头孢曲松 Ceftriaxone	R	四环素 Tetracycline	R	妥布霉素 Tobramycin	R
美洛培南 Meropenem	R	头孢哌酮 Cefoperazone	R	氯霉素 Chloramphenicol	R	氟罗沙星 Fleroxacin	R
多黏菌素B Polymyxin B	R	头孢他啶 Ceftazidime	R	克林霉素 Clindamycin	R	头孢他美 Cefetamet	R
美洛西林/舒巴坦 Mezlocillin/Sulbactam	R	头孢噻呋 Ceftiofur	R	红霉素 Erythromycin	R	万古霉素 Vancomycin	R
阿莫西林/舒巴坦 Amoxicillin/sulbactam	R	头孢比肟 Cefepime	R	头孢羟氨苄 Cefadroxil	R	利福平 Rifampicin	R
阿莫西林/克拉维酸 Amoxicillin/clavulanic acid	R	头孢喹肟 Cefquinome	R	呋喃妥因 Nitrofurantoin	R	头孢地嗪 Cefodizime	R
磺胺甲异恶唑 Sulfamethoxazole	R	左氧氟沙星 Levofloxacin	R	头孢匹胺 Cefpiramide	R	头孢噻吩 Cephalothin	R
氨苄西林/舒巴坦 Ampicillin/Sulbactam	R	司帕沙星 Sparfloxacin	R	头孢克肟 Cefixime	R	依替米星 Etimicin	R
磺胺甲恶唑 Sulfamethoxazole	S	美洛西林 Mezlocillin	R	罗红霉素 Roxithromycin	R	替考拉宁 Teicoplanin	R
头孢美唑Cefmetazole	S	庆大霉素Gentamicin	R	加替沙星Gatifloxacin	R	磷霉素Fosfomycin	R
大观霉素 Spectinomycin	S	杆菌肽 Bacitracin	R	链霉素 Streptomycin	R	头孢丙烯 Cefprozil	R
哌拉西林/他唑巴坦 Piperacillin/tazobactam	S	罗美沙星 Lomefloxacin	R	新生霉素 Novobiocin	R	替加环素 Tigecycline	R
替卡西林/克拉维酸 Ticacillin/clavulanic acid	S	阿奇霉素 Azithromycin	R	阿洛西林 Azlocillin	R	克拉霉素 Clarithromycin	R
头孢他啶/克拉维酸 Ceftazidime/clavulanic acid	S	米诺环 Minocycline	R	痢特灵 Furazolidone	R	头孢美唑 Cefmetazole	R
头孢噻肟/克拉维酸 Cefotaxime/clavulanic acid	S	氧氟沙星 Ofloxacin	R	依诺沙星 Enoxacin	R	环丙沙星 Ciprofloxacin	R
头孢哌酮/舒巴坦 Cefoperazone/sulbactam	S	青霉素G Penicillin	R	头孢孟多 Cefamandole	R	头孢氨苄 Cephalexin	R
氨曲南Aztreonam	S

抗生素Antibiotics	HN2106	抗生素Antibiotics	HN2106	抗生素Antibiotics	HN2106	抗生素Antibiotics	HN2106
亚胺培南Imipenem	R	头孢西丁Cefoxitin	R	庆大霉素Gentamicin	R	奈替米星Netilmicin	R
氨苄西林Ampicillin	R	头孢克洛Cefaclor	R	卡那霉素Kanamycin	R	诺氟沙星Norfloxacin	R
海他西林Hetacillin	R	头孢呋辛Cefuroxime	R	阿米卡星Amikacin	R	新霉素Neomycin	R
阿莫西林 Amoxicillin	R	头孢噻肟 Cefotaxime	R	链霉素 Streptomycin	R	羧苄西林 Carbenicillin	R
苯唑西林Oxacillin	R	头孢唑肟ceftizoxime	R	多西环素Doxycycline	R	哌拉西林Piperacillin	R
氯唑西林 Cloxacillin	R	头孢曲松 Ceftriaxone	R	四环素 Tetracycline	R	妥布霉素 Tobramycin	R
美洛培南 Meropenem	R	头孢哌酮 Cefoperazone	R	氯霉素 Chloramphenicol	R	氟罗沙星 Fleroxacin	R
多黏菌素B Polymyxin B	R	头孢他啶 Ceftazidime	R	克林霉素 Clindamycin	R	头孢他美 Cefetamet	R
美洛西林/舒巴坦 Mezlocillin/Sulbactam	R	头孢噻呋 Ceftiofur	R	红霉素 Erythromycin	R	万古霉素 Vancomycin	R
阿莫西林/舒巴坦 Amoxicillin/sulbactam	R	头孢比肟 Cefepime	R	头孢羟氨苄 Cefadroxil	R	利福平 Rifampicin	R
阿莫西林/克拉维酸 Amoxicillin/clavulanic acid	R	头孢喹肟 Cefquinome	R	呋喃妥因 Nitrofurantoin	R	头孢地嗪 Cefodizime	R
磺胺甲异恶唑 Sulfamethoxazole	R	左氧氟沙星 Levofloxacin	R	头孢匹胺 Cefpiramide	R	头孢噻吩 Cephalothin	R
氨苄西林/舒巴坦 Ampicillin/Sulbactam	R	司帕沙星 Sparfloxacin	R	头孢克肟 Cefixime	R	依替米星 Etimicin	R
磺胺甲恶唑 Sulfamethoxazole	S	美洛西林 Mezlocillin	R	罗红霉素 Roxithromycin	R	替考拉宁 Teicoplanin	R
头孢美唑Cefmetazole	S	庆大霉素Gentamicin	R	加替沙星Gatifloxacin	R	磷霉素Fosfomycin	R
大观霉素 Spectinomycin	S	杆菌肽 Bacitracin	R	链霉素 Streptomycin	R	头孢丙烯 Cefprozil	R
哌拉西林/他唑巴坦 Piperacillin/tazobactam	S	罗美沙星 Lomefloxacin	R	新生霉素 Novobiocin	R	替加环素 Tigecycline	R
替卡西林/克拉维酸 Ticacillin/clavulanic acid	S	阿奇霉素 Azithromycin	R	阿洛西林 Azlocillin	R	克拉霉素 Clarithromycin	R
头孢他啶/克拉维酸 Ceftazidime/clavulanic acid	S	米诺环 Minocycline	R	痢特灵 Furazolidone	R	头孢美唑 Cefmetazole	R
头孢噻肟/克拉维酸 Cefotaxime/clavulanic acid	S	氧氟沙星 Ofloxacin	R	依诺沙星 Enoxacin	R	环丙沙星 Ciprofloxacin	R
头孢哌酮/舒巴坦 Cefoperazone/sulbactam	S	青霉素G Penicillin	R	头孢孟多 Cefamandole	R	头孢氨苄 Cephalexin	R
氨曲南Aztreonam	S