质粒接合转移及其抑制剂的研究进展

doi:10.13560/j.cnki.biotech.bull.1985.2022-0688

摘要/Abstract

摘要：

随着细菌耐药性快速发展且不断出现新的耐药菌,临床抗感染治疗可选择的抗菌药物越来越少,不通过直接杀灭病原菌而寻求控制耐药基因的传播正成为一种新的耐药性防控策略。质粒是耐药基因最重要的载体之一,通过接合转移可在不同来源（如动物、人和环境）细菌间传播,对耐药性传播发挥了重要作用,因而抑制质粒接合转移被认为是防控耐药性传播的有效策略之一,受到越来越多研究者的重视。本文在简要介绍耐药性传播机制的基础上,阐述质粒接合转移过程及其机制,并总结了目前质粒接合抑制剂的研究进展,以期为耐药性防控新策略的研究提供参考和借鉴。

关键词: 耐药性, 质粒, 接合, 接合抑制剂

Abstract:

With the rapid development of antimicrobial resistance（AMR）and the increasing emergence of new antimicrobial-resistant bacteria, there are fewer and fewer antibiotics available for therapeutic options. Controlling the dissemination of resistance genes, without directly killing pathogens, is becoming a novel strategy to combat AMR. Plasmid acts as one of the most important vectors of resistance genes. It can be disseminated globally to bacterias of diverse sources（e.g., animal, human being, foods, and environment）through conjugation, and plays an important role in the transmission of AMR. Thus, inhibiting the conjugative transfer of plasmids is considered as a promising approach to control AMR and has been attracting more and more attentions of the researchers. This review briefly introduced the mechanism of AMR transfer, expounded the process and mechanism of plasmid conjugation, and summarized the progress of conjugation inhibitors,aiming to provide reference for the development of new strategies to control AMR.

Key words: resistance, plasmid, conjugation, conjugation inhibitor

刘艺云, 邓利敏, 岳慧颖, 岳超, 刘健华. 质粒接合转移及其抑制剂的研究进展[J]. 生物技术通报, 2022, 38(9): 35-46.

LIU Yi-yun, DENG Li-min, YUE Hui-ying, YUE Chao, LIU Jian-hua. Research Progress in Plasmid Conjugation and Its Inhibitors[J]. Biotechnology Bulletin, 2022, 38(9): 35-46.

图/表 7

参考文献 67

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类别 Categories	组分 Components	菌属 Species	质粒 Plasmids	耐药基因 Antimicrobial resistance genes	质粒接合频率下降倍数^d Fold reduction in plasmid transfer frequency	参考文献 References
脂肪酸类及其衍生物	油酸/亚油酸/脱氢戊烯酸（DHCA）	大肠杆菌→大肠杆菌	R388（IncW）^a, pKM101（IncN）^c, RP4（IncP）^c		DHCA（140 μmol/L）: 350倍	[25]
	2-炔基脂肪酸（2-HAD）	大肠杆菌→大肠杆菌	（IncF,IncW和IncH）^a（IncI,IncL/M和IncX）^b		（0.4 mmol/L）2-HDA : IncW,IncF和IncH（100倍）（1 mmol/L）2-HDA : IncI,IncL/M和IncX（6-25倍）	[27]
	Tanzawaic acids A和B	大肠杆菌→大肠杆菌	（IncW和IncFII）^a（IncFI,IncI,IncL/M,IncX,IncH）^b（IncN,IncP）^c		（0.4 mmol/L）TZA-B : 98倍	[29]
	2-溴软脂酸（2-BP）	大肠杆菌→大肠杆菌	R388（IncW）		（0.3 mmol/L）2-BP：98倍	[30]
磷酸化多糖类抗生素	（体外）黄霉素	粪肠球菌→粪肠球菌			8-16 mmol/L : 50-70倍	[36]
磷酸化多糖类抗生素	（体外）黄霉素	大肠杆菌→粪肠球菌	IncFIB,IncI1-Iγ,IncN	bla_CTX-M-15,bla_CTX-M-14, bl_aCTX-M-2	0.5 mmol/L FPL : 7.2-10.7倍	[37]
	（体内）黄霉素	大肠杆菌→沙门氏菌		str,tet,amp	饲料中添加64 ppm的黄霉素对接合转移具有抑制作用	[33]
亚水杨基酰肼类及其衍生物	BAR-072,BAR-073,UM-024	大肠杆菌→大肠杆菌	pKM101（IncN）		BAR-072 : 10倍	[40]
亚水杨基酰肼类及其衍生物	105055,239852	大肠杆菌→大肠杆菌	pKM101（IncN）		105055和239852 : 2倍	[41]
拟肽类化合物	C10,KSK85	大肠杆菌→大肠杆菌	pKM101（IncN）和R1-16（IncF）		（150 μm）C10 : 4倍	[44]
纳米材料	nano-Al₂O₃,nano-TiO₂,nano-SiO₂和nano-Fe₂O₃	大肠杆菌→大肠杆菌、沙门氏菌	RP4（IncP）		5000 mmol/L : 100倍＊	[48]
	CuO NPs / Cu²⁺	大肠杆菌→恶臭假单胞菌	RP4（IncP）		（5 mmol/L）CuO NPs : 40倍＊	[49]
	Fe₂O₃@MoS₂	大肠杆菌→大肠杆菌	RP4-7（IncP）		Fe₂O₃（0.1 g）@MoS₂: 100倍	[51]
	CeO₂ 纳米材料	大肠杆菌→大肠杆菌	RP4（IncP）		（1 000和5 000 μg/L）CeO2 NPs : 4倍	[53]
等离子体	等离子体	大肠杆菌→大肠杆菌		tet（C）,tet（W）,bla_TEM-1,aac（3）-II	9 kv（10 min）: 1 000倍	[58]
等离子体	NO₃^-,Cu²⁺,Fe²⁺	大肠杆菌→大肠杆菌		tet（C）,tet（W）,bla_TEM-1, aac（3）-II,intI1	Fe²⁺: 98倍	[59]
其他	双膦酸盐（PNP）	大肠杆菌→大肠杆菌	IncF		10 mmol/L（PNP）: 90倍	[60]
	单链Fv抗体	大肠杆菌→大肠杆菌	R388（IncW）		scFv-P4.E7: 20倍	[24]
	自由亚硝酸	大肠杆菌→大肠杆菌	RP4（IncP）		20 μg/L:100倍	[62]

类别 Categories	组分 Components	菌属 Species	质粒 Plasmids	耐药基因 Antimicrobial resistance genes	质粒接合频率下降倍数^d Fold reduction in plasmid transfer frequency	参考文献 References
脂肪酸类及其衍生物	油酸/亚油酸/脱氢戊烯酸（DHCA）	大肠杆菌→大肠杆菌	R388（IncW）^a, pKM101（IncN）^c, RP4（IncP）^c		DHCA（140 μmol/L）: 350倍	[25]
	2-炔基脂肪酸（2-HAD）	大肠杆菌→大肠杆菌	（IncF,IncW和IncH）^a（IncI,IncL/M和IncX）^b		（0.4 mmol/L）2-HDA : IncW,IncF和IncH（100倍）（1 mmol/L）2-HDA : IncI,IncL/M和IncX（6-25倍）	[27]
	Tanzawaic acids A和B	大肠杆菌→大肠杆菌	（IncW和IncFII）^a（IncFI,IncI,IncL/M,IncX,IncH）^b（IncN,IncP）^c		（0.4 mmol/L）TZA-B : 98倍	[29]
	2-溴软脂酸（2-BP）	大肠杆菌→大肠杆菌	R388（IncW）		（0.3 mmol/L）2-BP：98倍	[30]
磷酸化多糖类抗生素	（体外）黄霉素	粪肠球菌→粪肠球菌			8-16 mmol/L : 50-70倍	[36]
磷酸化多糖类抗生素	（体外）黄霉素	大肠杆菌→粪肠球菌	IncFIB,IncI1-Iγ,IncN	bla_CTX-M-15,bla_CTX-M-14, bl_aCTX-M-2	0.5 mmol/L FPL : 7.2-10.7倍	[37]
	（体内）黄霉素	大肠杆菌→沙门氏菌		str,tet,amp	饲料中添加64 ppm的黄霉素对接合转移具有抑制作用	[33]
亚水杨基酰肼类及其衍生物	BAR-072,BAR-073,UM-024	大肠杆菌→大肠杆菌	pKM101（IncN）		BAR-072 : 10倍	[40]
亚水杨基酰肼类及其衍生物	105055,239852	大肠杆菌→大肠杆菌	pKM101（IncN）		105055和239852 : 2倍	[41]
拟肽类化合物	C10,KSK85	大肠杆菌→大肠杆菌	pKM101（IncN）和R1-16（IncF）		（150 μm）C10 : 4倍	[44]
纳米材料	nano-Al₂O₃,nano-TiO₂,nano-SiO₂和nano-Fe₂O₃	大肠杆菌→大肠杆菌、沙门氏菌	RP4（IncP）		5000 mmol/L : 100倍＊	[48]
	CuO NPs / Cu²⁺	大肠杆菌→恶臭假单胞菌	RP4（IncP）		（5 mmol/L）CuO NPs : 40倍＊	[49]
	Fe₂O₃@MoS₂	大肠杆菌→大肠杆菌	RP4-7（IncP）		Fe₂O₃（0.1 g）@MoS₂: 100倍	[51]
	CeO₂ 纳米材料	大肠杆菌→大肠杆菌	RP4（IncP）		（1 000和5 000 μg/L）CeO2 NPs : 4倍	[53]
等离子体	等离子体	大肠杆菌→大肠杆菌		tet（C）,tet（W）,bla_TEM-1,aac（3）-II	9 kv（10 min）: 1 000倍	[58]
等离子体	NO₃^-,Cu²⁺,Fe²⁺	大肠杆菌→大肠杆菌		tet（C）,tet（W）,bla_TEM-1, aac（3）-II,intI1	Fe²⁺: 98倍	[59]
其他	双膦酸盐（PNP）	大肠杆菌→大肠杆菌	IncF		10 mmol/L（PNP）: 90倍	[60]
	单链Fv抗体	大肠杆菌→大肠杆菌	R388（IncW）		scFv-P4.E7: 20倍	[24]
	自由亚硝酸	大肠杆菌→大肠杆菌	RP4（IncP）		20 μg/L:100倍	[62]