抗菌适配体的筛选与应用进展

doi:10.13560/j.cnki.biotech.bull.1985.2022-0860

摘要/Abstract

摘要：

现代医学及分子生物技术当前所面临的一个重大挑战是探索新的治疗方案来应对细菌感染。因多重耐药细菌的比率不断增加，同时结合抗菌药物的功效、研发进程及成本，更加重了细菌感染治疗形势的严峻性。针对这一形势，最有希望的解决方案是寻找抗菌药物的替代来源，而经SELEX筛选获得的抗菌适配体是极具潜力的替代品。抗菌适配体可通过干扰细菌生化进程、控制细菌菌膜形成、阻断毒素侵染等机制降低细菌的致病能力。目前，基于适配体的抗菌策略主要包括单一适配体抑菌、适配体复合纳米材料、适配体复合抗生素等。本文总结了关于常见致病菌细胞或其相关成分适配体的筛选策略，并从适配体的裁剪修饰、抑菌机制及其在抑菌治疗中的应用等方面展开论述，展望了基于抗菌适配体的抑菌策略在感染治疗中的发展前景，旨在为致病菌引发的感染性疾病的诊治提供新思路。

关键词: 抗菌适配体, 筛选, 抑菌机制

Abstract:

One of the major challenges in modern medicine and molecular biotechnology is to explore new therapeutic options for bacterial infections. The increasing rates of multidrug-resistant bacteria, overlaid with the efficacy, development process, and cost of antimicrobial agents, has made the treatments of bacterial infections even more challenging. In response to this situation, the most promising solution is to find alternative sources of antibacterial drugs, and antibacterial aptamers obtained through SELEX screening are promising alternatives. Antibacterial aptamers can reduce the pathogenic abilities of bacteria by interfering with the biochemical processes of bacteria, controlling the formations of bacterial membrane and blocking the infections of toxins. Currently, aptamer-based antibacterial strategies mainly include single aptamer antibacteria, aptamer composite nanomaterials, aptamer composite antibiotics, etc. In this paper, the screening strategies of aptamers for common pathogenic cells or their related components are summarized, and the adaptation and modification of aptamers are discussed from the aspects of antimicrobial mechanism and its application in antimicrobial therapy. The development prospect of antimicrobial strategies based on antibacterial aptamers in the treatment of infection is prospected, aiming to provide new ideas for the diagnosis and treatment of infectious diseases caused by pathogenic bacteria.

Key words: antibacterial aptamer, selection, bacteriostatic mechanism

李典典, 粟元, 李洁, 许文涛, 朱龙佼. 抗菌适配体的筛选与应用进展[J]. 生物技术通报, 2023, 39(6): 126-132.

LI Dian-dian, SU Yuan, LI Jie, XU Wen-tao, ZHU Long-jiao. Progress in Selection and Application of Antibacterial Aptamers[J]. Biotechnology Bulletin, 2023, 39(6): 126-132.

图/表 3

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常见致病菌 Common pathogenic bacterium	菌型 Bacterial type	靶标 Target	适配体（类型） Aptamer（type）	序列 Sequence（5'-3'）	Kd/ （nmol·L^-1）	参考文献 Reference
沙门氏菌 Salmonellae	鼠伤寒沙门氏菌 S. typhimurium	IVB型菌毛 Type IVB pili	S-PS_8.4（RNA）	UCACUGUUAUCCGAUAGCAGCGCGGGAUGA	8.56	[7]
	鼠伤寒沙门氏菌 S. typhimurium	全细胞 Whole cells	ST-12, ST-33（DNA）	CTCCTCTGACTGTAACCACGGTGGTTTGATCACTATTGGGCCTTTGTGATGTCGGTAGT, CTCCTCTGACTGTAACCACGGTGGGAGAGATGCTATACAATCTTGTAAGGCGATGGACCG	4.5±0.4, 51.0±4.3	[8]
	肠炎沙门氏菌 S. enteritidis	SipA蛋白 SipA protein	Apt17（DNA）	TAGGGAAGAGAAGGACATATGATGCAATGGAACCGCTGAACGACCCTAG CATTATCAGTGTGGTTGACTAGTACATGACCACTTGA	114.9（27℃）, 63.4（37℃）	[9]
	猪霍乱沙门氏菌 S. choleraesuis	鞭毛蛋白 Flagellin	Aptamer 3（DNA）	GGCAGGACAACAGCGTGTAGTATCAGCTTACGGTG	41.0±2.0	[10]
结核分枝杆菌 Mycobacterium tuberculosis	H37Rv	PPK2	G9（DNA）	AACACATAGGTTTGGTTAGGTTGGTTGGTTGAATTA	870±220	[11]
结核分枝杆菌 Mycobacterium tuberculosis	H37Rv	全细胞 Whole cells	MS10-Trunc（DNA）	GGTGTGTTGACTGAGGGGGTGGGGTGGGTGGTGGTGGATATAGC	0.019	[12]
铜绿假单胞菌 Pseudomonas aeruginosa		C4-HSL	A16（DNA）	CCATCCACACTCCGCAAGTGGGGAGGGGAGAGACGACGATCCTGTGGGT TTTCTGCAGTGAGTCGTGTTTTCGACTTATTGCGTCGGCTGCCTCTACAT	28.47	[13]
金黄色葡萄球菌 Staphylococcus aureus		肠毒素A Enterotoxin A	S3（DNA）	CCCGCCTCTGAGCATTATTAATGTTATACCTTACGGCTGG	36.93±7.29	[14]

常见致病菌 Common pathogenic bacterium	菌型 Bacterial type	靶标 Target	适配体（类型） Aptamer（type）	序列 Sequence（5'-3'）	Kd/ （nmol·L^-1）	参考文献 Reference
沙门氏菌 Salmonellae	鼠伤寒沙门氏菌 S. typhimurium	IVB型菌毛 Type IVB pili	S-PS_8.4（RNA）	UCACUGUUAUCCGAUAGCAGCGCGGGAUGA	8.56	[7]
	鼠伤寒沙门氏菌 S. typhimurium	全细胞 Whole cells	ST-12, ST-33（DNA）	CTCCTCTGACTGTAACCACGGTGGTTTGATCACTATTGGGCCTTTGTGATGTCGGTAGT, CTCCTCTGACTGTAACCACGGTGGGAGAGATGCTATACAATCTTGTAAGGCGATGGACCG	4.5±0.4, 51.0±4.3	[8]
	肠炎沙门氏菌 S. enteritidis	SipA蛋白 SipA protein	Apt17（DNA）	TAGGGAAGAGAAGGACATATGATGCAATGGAACCGCTGAACGACCCTAG CATTATCAGTGTGGTTGACTAGTACATGACCACTTGA	114.9（27℃）, 63.4（37℃）	[9]
	猪霍乱沙门氏菌 S. choleraesuis	鞭毛蛋白 Flagellin	Aptamer 3（DNA）	GGCAGGACAACAGCGTGTAGTATCAGCTTACGGTG	41.0±2.0	[10]
结核分枝杆菌 Mycobacterium tuberculosis	H37Rv	PPK2	G9（DNA）	AACACATAGGTTTGGTTAGGTTGGTTGGTTGAATTA	870±220	[11]
结核分枝杆菌 Mycobacterium tuberculosis	H37Rv	全细胞 Whole cells	MS10-Trunc（DNA）	GGTGTGTTGACTGAGGGGGTGGGGTGGGTGGTGGTGGATATAGC	0.019	[12]
铜绿假单胞菌 Pseudomonas aeruginosa		C4-HSL	A16（DNA）	CCATCCACACTCCGCAAGTGGGGAGGGGAGAGACGACGATCCTGTGGGT TTTCTGCAGTGAGTCGTGTTTTCGACTTATTGCGTCGGCTGCCTCTACAT	28.47	[13]
金黄色葡萄球菌 Staphylococcus aureus		肠毒素A Enterotoxin A	S3（DNA）	CCCGCCTCTGAGCATTATTAATGTTATACCTTACGGCTGG	36.93±7.29	[14]